What is Cnidium Monnier Extracts?Pharmacology Actions and application of Cnidium Monnier and Osthol,C15H16O3,Osthola?

Contents

• Standard Description of Common cnidium fruit extract.
• Basic Botanical Data of Cnidium plant and Cnidium Seeds.
• Pharmacology Actions of of Osthol.
• Cnidium Monnier works for Eva and Adam.
• Application and Indications of Osthole.
• HPLC Determination of Osthole in Rat Plasma after Oral Administration of Fructus Cnidii Extract.
• Why must throw away Viagra and other out dated thing and choose Natural Cnidium Fruit?
• Safety and Acute toxicity
• Cnidium Monnier Research Update.
• Photo Gallery of Cnidium monnieri.

Cnidium Monnier Research Update.:

1.Osthol Mechanisms:

 Cnidium monnier (L) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction. Bioassay-directed fractionation led to the identification of four known coumarins osthole, imperatorin, xanthotoxin, and isopimpinellin from the ethanolic extract of the fruits of Cnidium monnier (L) Cusson.
 Furthermore, we investigated the cavernosal relaxant effect of osthole. In the present study, corpus cavernosal strip showed relaxation in response to osthole (0.1-30 .mu.M) in a dose-dependent manner. Corporal relaxation elicited by osthole was reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption, however, were not affected by indomethacin and tetradotoxin treatment.
 Additionally, osthole at the concentrations ranged from 1 to 30 .mu.M enhance the sodium nitroprusside (0.3 .mu.M)-induced, NO-mediated relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 .mu.M osthole.
 However, higher concentration of osthole (30 .mu.M) also enhanced forskolin-induced relaxation. The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the NO-stimulated cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting the phosphodiesterase.
 

2.Isolation of osthol and xanthotoxol from Common Cnidium Fruit using stepwise elution by high-speed counter-current chromatography.:

 Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of osthol and xanthotoxol from Cnidium monnieri (L.) Cusson (Common Cnidium Fruit) using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v), and (5:5:6:4, v/v), which had been selected by analytical high-speed counter-current chromatography. Using a preparative unit of the HSCCC centrifuge, about a 308 mg amount of the crude extract was separated, yielding 88.3 mg of osthol and 19.4 mg of xanthotoxol at a high purity of over 98%.

3.Isolation and purification of bergapten and imperatorin from the medicinal plant Cnidium monnieri using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase.:

 A high-speed counter-current chromatography (HSCCC) method was developed for the preparative separation and purification of bergapten and imperatorin from the Chinese medicinal plant Cnidium monnieri (L.) Cusson. The crude extract was obtained by extraction with ethanol from the dried fruits of Cnidium monnieri (L.) Cusson under sonication. Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (5:5:5:5, v/v/v/v) was successfully performed by increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml min(-1) after 180 min. The components purified and collected were analyzed by high-performance liquid chromatography. The method yielded 45.8 mg of bergapten at 96.5% purity and 118.3 mg of imperatorin at 98.2% purity from 500 mg of the crude extract in a single run. The recoveries of bergapten and imperatorin were 92.1 and 93.7%, respectively.
 

4.Inhibition of itch-scratch response by fruits of Cnidium monnieri in mice:

  We previously screened the anti-itching activities of 33 herbal medicines in substance P (SP)-induced itching model mice. One of the most potent antipruritogenic extracts, the methanol extract of fruits of Cnidium monnieri (Cnidii Fructus) was studied further. The chloroform-soluble fraction of the methanol extract markedly inhibited SP-induced scratching. Among 10 subfractions of the chloroform-soluble fraction, the CS-3 fraction had the most potent inhibitory effect on scratching. Each of 3 subfractions of CS-3 showed significant anti-scratching activities. However, inhibitory potencies were not different among the three and weaker than that of CS-3 itself at a same dose. These 3 subfractions of CS-3 mainly contained xanthotoxin, isopimpinellin, bergapten, imperatorin and osthol. Single administration of osthol did not inhibit SP-induced scratching, and imperatorin very weakly subsided scratching. These results suggest that the strong antipruritic action was focused on the CS-3 fraction of the C. monnieri methanol extract, and it might result from the combined effects of these coumarin derivatives, or by undetermined minor compounds.
 

5.Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus cavernosum.:

  Bioassay-directed fractionation led to the identification of four known coumarins, osthole (1), imperatorin (2), xanthotoxin (3), and isopimpinellin (4), from the ethanolic extract of the fruit of Cnidium monnieri (L.) Cusson. In phenylephrine (PE)-precontracted endothelium-intact rabbit corpus cavernosum, all four coumarins exhibited relaxing effect with the IC50 values for compounds 1, 2, 3, and 4 determined to be 2.14 +/- 0.73, 0.85 +/- 0.16, 1.24 +/- 0.45, and 18.4 +/- 8.10 microM, respectively. The four compounds were identified by comparison of their physical data (EIMS, 1H- and 13C-NMR) with those from published reports.
 

6.Determination of osthol and imperatorin in Cnidium monnieri (L.) cuss by fluorometry TLC scanning:

  The main active constituents--osthol and imperatorin were isolated from Cnidium monnieri (L.) Cuss and then used as standards for their determination in the crude drug by fluorometry TLCS. The fructus Cnidii was macerated with ethanol overnight and the ethanolic extract was spotted on a silica gel G-CMC Na plate. The plate was developed with n-hexane-ethyl acetate (7:3). The spot was excited by light of 365 nm, and determined in a Shimadzu CS-930 TLC scanner using a No. 2 filter. The peak areas of the two components were obtained, external standard method was used in the determination. The root, stem, leaf and flower of this plant were shown to contain no osthol and imperatorin, and the seed was found to contain 2.0-3.2% of osthol and 1.8-2.5% of imperatorin.
 

7.The Changes of Osthol Content in Cnidium monnieri in Different Growth Periods and under Salt Stress:

  Soil salinity under natural growth condition was much more than 4.0 times of that under salt stress, and besides, osthol could grow naturally under salt stress. Osthol content in each part of Cnidium monnieri was determined by HPLC in the growth period of seedling, vegetative, blooming and fruit under natural growth condition and in blooming and fruit period under salt stress. Results showed that osthol content was the highest during blooming and fruit period under different growth conditions. During blooming and fruit period the total osthol content was 316.86ug/g DW under salt stress, which were 1.9 times of that under natural growth condition, and was 160.00ug/g DW.
 

8.Determination of five coumarins in Cnidii Fructus by micellar electrokinetic capillary chromatography.:

  A micellar electrokinetic capillary chromatography (MEKC) method for the separation and quantification of the coumarins in Cnidii Fructus was developed for the first time. Within 25 minutes, 5 major coumarins were separated using 18 mM borate, 12 mM phosphate and 50 mM SDS (pH 9.2) containing 20 % methanol. The relative standard deviations of migration times and peak areas were less than 5 %. The total contents of the five coumarins in plants from different habitats ranged from 13.6 to 44.6 mg/g, and recoveries ranged from 96.0 to 102.8 %. The effects of buffer concentration, SDS, pH value and organic modifier on the separation were investigated.
 

9.Progress in study of chemical constituents and anti-tumor activities of Cnidium monnieri:

  The main pharmacological constituents of Chinese traditional medicine herb Cnidium monnieri are coumarin compounds and volatile oil. In addition, it contains monoterpene polyols, glucides, as well as recently discovered sesquiterpene components. In recent years, rather active investigations of its anti-tumor were performed at home and abroad. C. monnieri possesses multi-aspect and comprehensive anti-tumor functions, involving directly tumor-inhibitory activity, anti-mutagenicity, reversing multi-drug tolerance of tumor, as well as improving immune functions and so on. In this review, chemical constituents, anti-tumor activities and relevant investigations of Fructus Cnidii were summarized recent decade.
 

10.Study on extraction of coumarins in Cnidium monieri by supercritical CO2 and separation of compositions analysis:

  To analyze the chemical constituents of supercritical carbon dioxide extraction products from Cnidium monieri. Method: Four-factor and three-level orthogonal experimental design was used to optimize the SFE conditions as guided by the content of total coumarins in the extract. The chemical constituents were separated and identified by recrystalization. Result: Optimum extraction process was established: 25 MPa as extraction pressure, 50 degrees C as extraction temperature, 6.5 MPa as separation pressure and 60 degrees C as separation temperature. CONCLUSION: Changes in extraction pressure, temperature, time, pulverized degree and separation pressure affect the extracting results remarkably. The two kinds of chemical constituents were separated by recrystallization from C. monieri and identified by the methods of UV, IR, MS, NMR.
 

11.Analysis on intraspecific variation of Cnidium monnieri by RAPD:

  To study the genetic variation of Cnidium monnieri from different regions. Methods: Random amplified polymophic DNA technique was used to analyze genetic polymorphy of Cnidium monnieri from 9 different regions, and dendrogram was constructed by UPGMA. Results: 20 random primers were used for polymorphic selection. A total of 75 bands were amplified, 64 of which were polymorphism. CONCLUSION: The smaller the geographic distances between two Cnidium monnieri, the smaller genetic differences. However, it should not be overlooked that natural environment, especially the local ecological conditions may also show some influences on the genetic variations among different C. monnieri samples.
 

12.Determination of chemical constituents of the essential oil from Cnidium monnieri by GC-MS:

  The chemical components of the essential oil from Cnidium monnieri (L.) Cusson were analyzed by GC-MS. Method: The essential oil was extracted from Cnidium monnieri (L.) Cusson by steam distillation, the components analyzed with the different kinds of capillary columns, the optimum separated and analytical conditions were researched, the amount of the components from the essential oil were determinated by normalization method. The separated components were identified by GC-MS. Results: 50 components composed of about 86% of the total essential oil were separated and identified. CONCLUSION: The method is reliable and stable.
 

13.Anti-allergic effects of cnidii monnieri fructus (dried fruits of Cnidium monnieri) and its major component, osthol.:

  Anti-allergic effects (types I and IV) of the 70% ethanol extract (CM-ext) obtained from Cnidii Monnieri Fructus (dried fruits of Cnidium monnieri) were investigated on 48 h homologous passive cutaneous anaphylaxis (PCA), 2, 4-dinitrofluorobenzene (DNFB)-induced contact dermatitis and picryl chloride (PC)-induced contact dermatitis in experimental animals. CM-ext showed inhibitory effects on these allergic models. Osthol isolated from CM-ext also had the inhibitory effects. These results suggested that Cnidii Monnieri Fructus might be useful as an agent for allergic diseases and that its anti-allergic effect was partially attributable to a coumarin derivative, osthol.
 

14.Effects of coumarins from cnidium monnieri on the function of pituitary-adrenocortical axis in kidney yang deficiency rats:

  To observe the effect of Cnidium monnieri in Kidney Yang Deficiency rats. Methods: Rats were injected intraperitoneally with hydrocortisone acetate to replicate the animal model of Kidney Yang Deficiency. Osthol, total-coumarins (TCR) from the fruit of Cnidium monnieri and positive control drug (PCD) were administered orally to model rats. The plasma levels of corticosterone (B), adrenocorticotropic hormone (ACTH), renin (PRA), angiotensin-II (AT-II) and aldosterone (ALD) were determined by radioimmunoassay. Results: Compared with those in normal rats, the levels of B and ACTH in the plasma of model rats lowered significantly (P less than 0.01), the levels of B and ACTH of treatment groups were higher than those of model group, while the levels of PRA, AT-II and ALD had no significant difference (P bigger than 0.05). CONCLUSION: The osthol, TCR have the effects in protecting and strengthening the function of pituitary-adrenocortex axis.
 

15.Mechanism of the antiasthmatic effect of total coumarins in the fruit of Cnidium monnieri (L.)Cuss.:

  Total coumarins in the fruit of Cnidium monnieri show a marked protective effect against bronchial asthma induced by inhalation of histamine in conscious guinea pig. In vitro these total coumarins can relax the contraction of the isolated trachea in guinea pigs induced by histamine as well as increase the perfusion rate of isolated lung preparation of guinea pig. These actions, however, may be blocked by propranolol. Besides, these coumarins.

16.Centrally acting muscle relaxant effect of phthalides (ligustilide, cnidilide and senkyunolide) obtained from Cnidium officinale Makino:

Yakugaku Zasshi. 1989 Jun;109(6):402-6.
 The present study was carried out to elucidate a centrally acting muscle relaxant effect of chloroform soluble fraction and its component, namely, ligustilide, cnidilide and senkyunolide obtained from the rhizome of Cnidium officinale Makino. These three compounds were isolated from the chloroform soluble fraction by column chromatography on silica gel. The centrally acting muscle relaxant effect was investigated on the crossed extensor reflex in anesthetized rats and these samples were suspended in 0.5% carboxymethyl cellulose solution and administered i.p. These three compounds as well as the chloroform soluble fraction depressed the reflex response. The depressive potencies among them were almost the same and their potencies were also the same or somewhat weaker as that of mephenesin. As a curare-like action was not observed, a muscle relaxation induced by these phthalide compounds is considered to be due to central origin.

17.Effects of extract from a herbal drug, cnidium rhizome (senkyu), on contraction, heart rates and membrane potentials of isolated guinea pig atria:

Yakugaku Zasshi. 1989 Sep;109(9):662-71.
 Effects of extract from a herb, Cnidium rhizome (Senkyu), on isolated guinea pig atria were investigated pharmacologically and electrophysiologically. The methanol extract from Cnidium rhizome decreased the contraction and slightly increased the heart rates of the isolated atria. Extracts from five other herbs, such as Japanese anglica root (Toki), Peony root (Shakuyaku), Moutan bark (Botanpi), Glycyrrhiza (Kanzo), Bupleurum (Saiko), affected neither the contraction nor the heart rates. The methanol extract from Cnidium rhizome was fractionated with chloroform and water fractions. The chloroform fraction exerted potent negative inotropic and chronotropic effects in isolated atria. The contraction was attenuated by two major components in the chloroform fraction, ligustilide and senkyunolide, but the heart rates were scarcely affected by these components. The chloroform fraction induced changes in resting potentials and configurations of normal action potentials recorded in the isolated left atria: the resting potentials were depolarized, and the upstroke velocity of the action potentials decreased. Neither ligustilide nor senkyunolide exerted such effects. The upstroke velocity of action potentials recorded in partially depolarized atria was reduced by the chloroform fraction as well as ligustilide and senkyunolide. The mechanisms underlying the effects of the extract from Cnidium rhizome were discussed.

18.Determination of osthol and imperatorin in Cnidium monnieri (L.) cuss by fluorometry TLC scanning:

Yao Xue Xue Bao. 1990;25(7):530-3.
 The main active constituents--osthol and imperatorin were isolated from Cnidium monnieri (L.) Cuss and then used as standards for their determination in the crude drug by fluorometry TLCS. The fructus Cnidii was macerated with ethanol overnight and the ethanolic extract was spotted on a silica gel G-CMC Na plate. The plate was developed with n-hexane-ethyl acetate (7:3). The spot was excited by light of 365 nm, and determined in a Shimadzu CS-930 TLC scanner using a No. 2 filter. The peak areas of the two components were obtained, external standard method was used in the determination. The root, stem, leaf and flower of this plant were shown to contain no osthol and imperatorin, and the seed was found to contain 2.0-3.2% of osthol and 1.8-2.5% of imperatorin.

19.Mechanism of the antiasthmatic effect of total coumarins in the fruit of Cnidium monnieri (L.)Cuss:

Zhongguo Zhong Yao Za Zhi. 1990 May;15(5):304-5, 320.
 Total coumarins in the fruit of Cnidium monnieri show a marked protective effect against bronchial asthma induced by inhalation of histamine in conscious guinea pig. In vitro these total coumarins can relax the contraction of the isolated trachea in guinea pigs induced by histamine as well as increase the perfusion rate of isolated lung preparation of guinea pig. These actions, however, may be blocked by propranolol. Besides, these coumarins cannot increase the heart rate and arterial blood pressure in anesthetized rats. All this shows that the antiasthmatic effect of total coumarins in the fruit of Cnidium monnieri is mediated by beta 2-receptor.

20.Antimutagenicity screening of water extracts from 102 kinds of Chinese medicinal herbs:

Zhongguo Zhong Yao Za Zhi. 1990 Oct;15(10):617-22, 640
 Our observation shows that out of 102 kinds of Chinese medicinal herbs tested, 17 have remarkable antimutagenic effect on the mutation induced by aflatoxin B1, in Ames test. Among the 17 herbs Glycyrrhiza uralensis, Bupleurm chinense, Portulaca grandiflora and Cnidium monnieri have been found in other tests to be effective against mutagenesis induced by cyclophosphamide in mice.

21.A pharmacognostical study on the fruits of Cnidium monnieri (L.) Cuss:

Zhongguo Zhong Yao Za Zhi. 1990 Nov;15(11):649-52, 701.
 The fruits of three species are used as the Chinese drug "Shechuangzi", namely Cnidium monnieri, C. monnieri var. formosana and C. japonicum, among which only C. monnieri is the real sort. The authors have distinguished them by macroscopic and microscopic structures and TLC. The total coumarin, trace element and amino acid contents are reported.

22.Studies on the quality of fructus Cnidii--comparison of antibacterial action:

Zhongguo Zhong Yao Za Zhi. 1991 Aug;16(8):451-3, 510.
 Comparative studies on antibacterial and antifungal action of the fruits of C. monnieri from four habitats and two other species of Cnidium showed they had inhibitory potency to some bacterial and fungi in vitro. C. monnieri and C. salium were more effective than C. dahuricum in antibacterial activities. C. monnieri had higher antifungal effect than C. salium and C. dahuricum.

23.An acidic polysaccharide having immunological activities from the rhizome of Cnidium officinale.:

Chem Pharm Bull. 1992 Nov;40(11):3025-9.
 An acidic polysaccharide, designated as cnidirhan AG, was isolated from the rhizomes of Cnidium officinale Makino. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 5.1 x 10(4). It showed pronounced reticuloendothelial system-potentiating activity in a carbon clearance test, and had a remarkable effect on both anti-complementary and alkaline phosphatase-inducing activities. It is composed of L-arabinose: D-galactose: D-glucuronic acid in the molar ratio of 2:6:1, in addition to small amounts of O-acetyl groups. Methylation analysis, carbon-13 nuclear magnetic resonance, controlled Smith degradation and limited acid hydrolysis indicated that the core structural features of cnidirhan AG include a backbone chain composed of beta-1,3-linked D-galactose residues. Some of the galactose units in the backbone carry beta-D-galactosyl side chains at position 6. Both alpha-L-arabinosyl arabinose side chains and terminal beta-D-glucuronic acid residues are linked to the core galactan units.

24.Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells.:

Jpn J Pharmacol. 1992 Dec;60(4):397-401.
 Antiproliferative effects of the Japanese-Sino medicine Shimotsu-to (a combined prescription of cnidium rhizome, angelica root, peony root and rehmannia root) were investigated in the primary culture of smooth muscle cells (SMC) of mouse aorta. Fetal bovine serum (10%)-induced proliferation of primary cultured SMC was inhibited by Shimotsu-to at 4, 20, 100 or 500 micrograms/ml. The inhibitory effect was selective on SMC and due to cnidium rhizome or angelica root. The IC50 values of senkyunolide H, senkyunolide A, ligustilide and butylidenephthalide derived from cnidium were below 0.1, 1.52, 1.68 and 3.25 micrograms/ml, respectively. These results indicate that the antiproliferative effect of Shimotsu-to may depend on these cnidium-derived phthalides.

25.Effects of total coumarins, essential oil and water extracts of Cnidium monnieri on plasma prostaglandin and cyclic nucleotide in the rats of kidney-yang insufficiency:

Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 Feb;13(2):100-1, 70.
 Effects of total coumarins, essential oil and water extracts of Cnidium monnieri on plasma prostaglandin (PGE2 and PGF2 alpha) and cyclic nucleotide levels in rats of Kidney-Yang insufficiency were studied. 55 rats were divided randomly into 5 groups, Group I was administered orally with saline (normal group), group II was injected with intraperitonally hydrocortison acetate to induce Kidney-Yang insufficiency (control group), group III, group IV and group V (experimental groups) were injected with hydrocortison acetate, the same as group II, and administered orally with the total coumarins, essential oil and water extracts of Fructus Cnidii respectively. The levels of plasma PGE2, PG2 alpha and plasma cAMP, cGMP were measured. In group II, in comparing with those of group I, the levels of plasma PGE2, and PGF2 alpha decreased significantly (P < 0.01), and the value of cAMP/cGMP also lowered obviously (P < 0.01) due to the significant reduction of cAMP and insignificant change of cGMP. In group III and group V, the above-mentioned indices changed significantly (P < 0.01 or 0.05) compared with those of group II, and after treatment it normalized basically in comparing with those of group I. In group IV, those indices didn't change regularly and apparently as group III and group V did, compared with group II, and could not normalize satisfactorily. It is suggested that the coumarins in the fruit of Cnidium monnieri are probably the effective ingredients to invigorate Kidney and strengthen Yang, while the efficacy of essential oil remained unconfirmed.

26.Chemical structure-activity of cnidium rhizome-derived phthalides for the competence inhibition of proliferation in primary cultures of mouse aorta smooth muscle cells.:

Jpn J Pharmacol. 1993 Nov;63(3):353-9.
 Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6,7-dihydroligustilide) > senkyunolide H ((Z)-6,7-dihydroxy-6,7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6,7-dihydroxy-3,6,7,8-tetrahydroligustilide) > senkyunolide I ((E)-6,7-dihydroxy-6,7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3,8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the (Z)-6,7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.

27.Characterization of a novel glucan, which exhibits reticuloendothelial system-potentiating and anti-complementary activities, from the rhizome of Cnidium officinale.:

Chem Pharm Bull. 1994 Mar;42(3):630-3.
 A novel glucan, called cnidirhan SI, was isolated from the rhizome of Cnidium officinale Makino. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 1.3 x 10(4). It is composed of D-glucose alone, in addition to small numbers of O-acetyl groups. Methylation analysis, nuclear magnetic resonance and enzymic degradation studies indicated it has a high-branched glucan type structure composed of alpha-1,4-linked D-glucopyranose residues with both 3,4- and 4,6-branching points. The glucan showed significant reticuloendothelial system-potentiating activity in a carbon clearance test, as well as pronounced anti-complementary activity. This substance is the first example of a branched alpha-glucan with phagocytosis-stimulating and anti-complementary activities.

28.Effect of total coumarins from dried fruits of Cnidium monnieri on glucocorticoid-induced osteoporosis in rats:

Zhongguo Yao Li Xue Bao. 1994 Jul;15(4):371-4.
 Twenty-four 3-month-old male SD rats were divided into 3 groups: Group 1--control (ig water). Group 2--ig prednisone 45 micrograms.kg-1 twice a week. Group 3--treated with total coumarins of dried fruits of Cnidium monnieri (L) Cuss (TCCM) and prednisone. TCCM was given ig 5 g.kg-1, 6 days per week. After 90 d, rats were killed. The proximal tibiae of rats were processed undecalcified for histomorphometric analysis. In comparison with control rats, the bone resorption was enhanced and bone formation decreased. The trabecular bone areas were characterized by reduction of 40% in rats which received prednisone. Trabecular bone areas of rats treated with TCCM increased 56% compared with rats receiving prednisone. All indices of bone histomorphometry were near to those in the control. The results showed that TCCM prevented glucocorticoid-induced osteoporosis.

29.Characterization of a novel heteroglucan from the rhizome of Cnidium officinale exhibiting high reticuloendothelial system-potentiating and anti-complementary activities.:

Biol Pharm Bull. 1994 Jul;17(7):973-6.
 A novel beta-heteroglucan, called cnidirhan SIIA, was isolated from the rhizome of Cnidium officinale MAKINO. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was more than 1 x 10(7). It was composed of D-glucose, D-galactose and L-arabinose in the molar ratio of 85:5:8, in addition to small numbers of O-acetyl groups. Methylation analysis and nuclear magnetic resonance studies indicated its main structural features composed of beta-1,6-linked D-glucopyranosyl residues with both 3,6- and 4,6-branching points. In addition, it has both beta-1,4-linked L-arabinopyranosyl and beta-1,6-linked D-galactopyranosyl residues. The polysaccharide showed very pronounced reticuloendothelial system-potentiating activity in a carbon clearance test, as well as a marked anti-complementary activity.

30.Effects of osthol and total-coumarins from Cnidium monnieri on immunological function in kidney yang deficiency mice:

Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995 Sep;15(9):547-9.
 Mice were injected intraperitoneally with hydrocortisone acetate to replicate the animal model of Kidney Yang Deficiency (KYD). Osthol and total-coumarins (TCR) from the fruit of Cnidium monnieri were administered orally to model mice. The effects of osthol and TCR on the immunological function of the KYD mice were observed. The results showed that compare with those in normal mice, the percentage of phagocytosis and the index of macrophage phagocytosis, the level of serum hemolysin and the proliferation of lymphocytes lowered significantly (P < 0.01) in model mice. It was shown that administering osthol or TCR could notably (P < 0.01) prevent the above-mentioned lowering in model mice, revealing that osthol and TCR could improve the immunological function of KYD mice.

31.Studies on Cnidium fruits by stereological method and computer image analysis:

Zhongguo Zhong Yao Za Zhi. 1996 Jan;21(1):9-11, 62.
 The fruits, pollen grains, vascular bundles, stomata and endosperm cells of 4 Cnidium species were studied and determined by stereological method and computer image analysis technique. Statistical data were presented. In the volume of fruit and the area of vascular bundle, Cnidium dahuricum is the biggest, then C. salinum, C. japonicum and C. monnieri successively. In the volume of pollen grain,C. salinum is the biggest, followed by C. dahuricum, C. japonicum and C. monnieri in succession. In the volume of endosperm cell, C. dahuricum is also the biggest, and then C. japonicum, C. salinum and C. monnieri in order.

32.Inhibitory effects of traditional Chinese medicine Shimotsu-to and its included crude fractions on adjuvant-induced chronic inflammation of mice.:

Biol Pharm Bull. 1996 Jan;19(1):47-52.
 Effects of a traditional Chinese medicine, Shimotsu-to (a combined prescription of cnidium rhizome, peony root, angelica root and rehmannia root), and its included crude fractions were investigated on an adjuvant-induced chronic inflammation model of mice. The aqueous extract (30, 100 and 300 mg/kg, i.p.) of Shimotsu-to reduced the carmine content, granuloma weight, inflammation cell count and pouch fluid weight in the inflammation model, respectively. The extract of Shimotsu-to without cnidium at the same doses did not produce significant changes in these four inflammatory parameters. The same doses of extracts of Shimotsu-to without peony, and without angelica, weakly reduced these parameters, except for pouch fluid weight. The extract (30, 100 and 300 mg/kg) of cnidium significantly reduced these four parameters. The same doses of peony extract reduced carmine content, granuloma weight and pouch fluid weight, but less than those of the cnidium extract. The extract of cnidium and peony at the same doses reduced in an additive manner these inflammatory parameters in their combination. These results demonstrated that the Shimotsu-to extract reduced angiogenesis, granuloma formation, inflammatory cell migration and pouch fluid exudation in the adjuvant-induced chronic inflammation model. Cnidium represented the main ingredient for producing the anti-chronic inflammatory effects of Shimotsu-to extract. Cnidium and peony exhibited additive anti-inflammatory effects in combination.

33.Effects of coumarins from cnidium monnieri on the function of pituitary-adrenocortical axis in kidney yang deficiency rats:

Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Apr;17(4):227-9.
 OBJECTIVE: To observe the effect of Cnidium monnieri in Kidney Yang Deficiency rats. METHODS: Rats were injected intraperitoneally with hydrocortisone acetate to replicate the animal model of Kidney Yang Deficiency. Osthol, total-coumarins (TCR) from the fruit of Cnidium monnieri and positive control drug (PCD) were administered orally to model rats. The plasma levels of corticosterone (B), adrenocorticotropic hormone (ACTH), renin (PRA), angiotensin-II (AT-II) and aldosterone (ALD) were determined by radioimmunoassay. RESULTS: Compared with those in normal rats, the levels of B and ACTH in the plasma of model rats lowered significantly (P < 0.01), the levels of B and ACTH of treatment groups were higher than those of model group, while the levels of PRA, AT-II and ALD had no significant difference (P > 0.05). CONCLUSION: The osthol, TCR have the effects in protecting and strengthening the function of pituitary-adrenocortex axis.

34.Effects of fructus cnidii coumarins compared with nilestriol on osteoporosis in ovariectomized rats:

Zhongguo Yao Li Xue Bao. 1997 May;18(3):286-8.
 AIM: To compare the total coumarins from dried fruits of Cnidium monnieri (TCCM) and nilestriol (Nil) against osteoporosis. METHODS: SD rats (40, female, 3-month-old) were randomly divided into basal control, age control, ovariectomized (Ova), Ova + TCCM 67 mg.kg-1, Ova + TCCM 200 mg.kg-1, 6 times a week, and Ova + Nil 1 mg.kg-1, i.g. once a week. After 12 wk, sections (20 microns) of proximal tibiae were examined histologically. RESULTS: Ova reduced markedly the trabecular bone mass due to bone resorption excessed bone formation (% Tb. Ar -59%). Treatment with TCCM 67 mg.kg-1 partly suppressed bone turnover, but did not inhibit bone loss in Ova rats (% Tb.Ar -43%). Treatment with TCCM 200 mg.kg-1 and Nil 1 mg.kg-1 increased the trabecular area (% Tb. Ar +100% and +274%). CONCLUSION: Nil was more potent than TCCM in protecting against osteoporosis in Ova rats via supression of bone turnover.

35.Effects of total coumarins of Cnidium monnieri on bone density and biomechanics of glucocorticoids-induced osteoporosis in rats.:

Zhongguo Yao Li Xue Bao. 1997 Nov;18(6):519-21
 AIM: To evaluate the effects of total coumarins from dried fruits of Cnidium monnieri (TCCM) on glucocorticoids (GC)-induced osteoporosis (OP) in rats. METHODS: Single photon absorptiometric and biomechanical character measurements of femurs were used. RESULTS: The bone density (BD) indices in proximal, middle, and distal segments in GC group were decreased by 12% (P < 0.05), 14% (P < 0.05), and 12% (P < 0.05), respectively vs control group. The BD on proximal, middle, and distal segments in GC-TCCM group were increased by 26% (P < 0.01), 34% (P < 0.01), and 31% (P < 0.01), respectively vs GC group. The biomechanical competence in femoral middle segments in GC group tended to decrease vs control group. In GC-TCCM group, the torsional strength, energy, maximal torsional angle, and rigidity were increased by 15% (P < 0.05), 32% (P < 0.05), 14% (P > 0.05), and 13% (P > 0.05), respectively vs the GC group. CONCLUSION: TCCM not only prevented glucocorticoids-induced osteoporosis but also increased the torsional strength of femurs in rats.

36.Coumarins from the fruits of Cnidium monnieri.:

J Nat Prod. 2000 Apr;63(4):485-8.
 Two novel biscoumarins, cnidimonal (1) and cnidimarin (2), and two new coumarin derivatives, 5-formylxanthotoxol (3) and 2'-deoxymeranzin hydrate (4), were isolated from a traditional Chinese crude drug, the fruits of Cnidium monnieri, together with 15 known compounds. Among the known compounds, five of the minor compounds were isolated for the first time from this plant. The structures of 1-4 were determined with the use of spectroscopic methods.

37.Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro.:

J Urol. 2000 Jun;163(6):1975-80.
 PURPOSE: We investigated the cavernosal relaxant effect of osthole, a coumarin isolated from Cnidium monnier (L.) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were precontracted with phenylephrine. Corporal relaxation evoked by osthole was then determined in the absence and presence of nitric oxide synthase inhibitor (L-NAME), soluble guanylate cyclase inhibitor (ODQ), cyclooxygenase inhibitor (indomethacin), tetradotoxin, and after endothelium deprivation. RESULTS: Corpus cavernosal strips showed relaxation in response to osthole (0.1 approximately 30 microM) in a dose-dependent manner. These effects were reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption. However, they were not affected by indomethacin and tetradotoxin treatment. Osthole pretreatment (from 1 to 30 microM) enhanced the sodium nitroprusside (0.3 microM)-induced relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 microM osthole. However, this effect was abolished in the presence of zaprinast. Additionally, a higher concentration of osthole (30 microM) also enhanced forskolin-induced relaxation. CONCLUSION: The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase.

38.Inhibitory effects of methanol extracts of herbal medicines on substance P-induced itch-scratch response.:

Biol Pharm Bull. 2000 May;23(5):599-601.
 In a search for new anti-pruritic drugs we screened methanol extracts of 33 herbal medicines which have been used for cutaneous diseases for their antipruritic activity using substance P (SP) as a pruritogen in mice. When administered perorally 30 min before SP injection, methanol extracts of 6 of these herbal medicines, the root of Scrophularia ningpoensis Hemsl., the root of Patrinia villosa (Thunb.) Juss, the fruit of Forsythia suspenna Vahl, the rhizome of Cimicifuga dahurica (Turcz.) Maxim., the aerial part of Schizonepeta tenuifolia Briq. and the fruit of Cnidium monnieri (L.) Cuss, inhibited SP-induced itch-scratch response at a dose of 200 mg/kg with-out affecting locomotor activity. Dose dependence of these 6 extracts (50-500 mg/kg) was investigated and all of them inhibited SP-induced itch-scratch response, with extracts from Scrophularia ningpoensis, Schizonepeta tenuifolia and Cnidium monnieri showing particularly significant inhibition. The results suggest that these 6 methanol extracts have inhibitory activity against SP-induced itching.

39.Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus cavernosum.:

Planta Med. 2001 Apr;67(3):282-4.
 Bioassay-directed fractionation led to the identification of four known coumarins, osthole (1), imperatorin (2), xanthotoxin (3), and isopimpinellin (4), from the ethanolic extract of the fruit of Cnidium monnieri (L.) Cusson. In phenylephrine (PE)-precontracted endothelium-intact rabbit corpus cavernosum, all four coumarins exhibited relaxing effect with the IC50 values for compounds 1, 2, 3, and 4 determined to be 2.14 +/- 0.73, 0.85 +/- 0.16, 1.24 +/- 0.45, and 18.4 +/- 8.10 microM, respectively. The four compounds were identified by comparison of their physical data (EIMS, 1H- and 13C-NMR) with those from published reports.

40.Inhibition of itch-scratch response by fruits of Cnidium monnieri in mice.:

Biol Pharm Bull. 2001 Sep;24(9):1012-5.
 We previously screened the anti-itching activities of 33 herbal medicines in substance P (SP)-induced itching model mice. One of the most potent antipruritogenic extracts, the methanol extract of fruits of Cnidium monnieri (Cnidii Fructus) was studied further. The chloroform-soluble fraction of the methanol extract markedly inhibited SP-induced scratching. Among 10 subfractions of the chloroform-soluble fraction, the CS-3 fraction had the most potent inhibitory effect on scratching. Each of 3 subfractions of CS-3 showed significant anti-scratching activities. However, inhibitory potencies were not different among the three and weaker than that of CS-3 itself at a same dose. These 3 subfractions of CS-3 mainly contained xanthotoxin, isopimpinellin, bergapten, imperatorin and osthol. Single administration of osthol did not inhibit SP-induced scratching, and imperatorin very weakly subsided scratching. These results suggest that the strong antipruritic action was focused on the CS-3 fraction of the C. monnieri methanol extract, and it might result from the combined effects of these coumarin derivatives, or by undetermined minor compounds.

41.Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells:

Biochem Pharmacol. 2002 Jan 15;63(2):199-206.
 The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique. Osthole (0.3-100 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of the osthole-induced inhibition of I(Ca,L) was 4 microM. The presence of osthole (3 microM) shifted the steady state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. Osthole (3 microM) also produced a prolongation in the recovery of I(Ca,L) inactivation. Although osthole might suppress phosophodiesterases to increase intracellular adenosine-3',5'-cyclic monophosphate (cyclic AMP) or guanosine-3',5'-cyclic monophosphate (cyclic GMP), sp-cAMPS did not affect I(Ca,L) and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of I(Ca,L) was not associated with intracellular cyclic AMP or GMP. However, no effect of osthole on voltage-dependent K(+) outward current was observed. Under a current-clamp mode, osthole could decrease the firing frequency of action potentials. Therefore, the channel-blocking properties of osthole may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

42.Antipruritic effect of Cnidii Monnieri Fructus (fruits of Cnidium monnieri CUSSON).:

Biol Pharm Bull. 2002 Feb;25(2):260-3.
 Antipruritic effects of 70% ethanol extract (CM-ext) of Cnidii Monnieri Fructus (dried fruits of Cnidium monnieri CUSSON, Umberifferae) were investigated. In mice, an oral administration of CM-ext (200 and 500 mg/kg) inhibited compound 48/80-induced scratching behavior without influence on spontaneous locomotion. Isopimpinellin (3) and osthol (1), coumarin derivatives isolated from CM-ext, showed an inhibitory effect on compound 48/80-induced scratching behavior.

43.Effects of Kangen-karyu on coagulation system and platelet aggregation in mice.:

Biol Pharm Bull. 2002 Apr;25(4):523-5.
 Kangen-karyu (KGK) is a herbal formula created under the theory of traditional Chinese herbal medicine to invigorate the blood and dispel blood stasis. It contains 6 herbs: peony root, cnidium rhizome, safflower, cyperus rhizome, saussurea root (JP XIV), and Salvia miltiorrhiza root. The present study has been conducted to evaluate the in vivo anti-thrombotic activity of KGK using normal mice. Three consecutive days of oral administration of KGK to mice significantly extended tail-bleeding time and suppressed ex vivo platelet aggregation, while it did not extend the prothrombin time of plasma. It was revealed that the anti-thrombotic effects of KGK did not depend on the downregulation of the coagulation system, but depended in part on the inhibition of platelet aggregation. These results explain one of the pharmacological activities of KGK to invigorate the blood and dispel blood stasis.

44.Anti-allergic effects of cnidii monnieri fructus (dried fruits of Cnidium monnieri) and its major component, osthol.:

Biol Pharm Bull. 2002 Jun;25(6):809-12
 Anti-allergic effects (types I and IV) of the 70% ethanol extract (CM-ext) obtained from Cnidii Monnieri Fructus (dried fruits of Cnidium monnieri) were investigated on 48 h homologous passive cutaneous anaphylaxis (PCA), 2, 4-dinitrofluorobenzene (DNFB)-induced contact dermatitis and picryl chloride (PC)-induced contact dermatitis in experimental animals. CM-ext showed inhibitory effects on these allergic models. Osthol isolated from CM-ext also had the inhibitory effects. These results suggested that Cnidii Monnieri Fructus might be useful as an agent for allergic diseases and that its anti-allergic effect was partially attributable to a coumarin derivative, osthol.

45.Anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus.:

J Ethnopharmacol. 2002 Aug;81(3):373-9.
 This study investigated the anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus by using cultured glomerular capillary endothelial cells (GECs), chorioallantoic membrane (CAM) and rat cornea. Treatment of GECs with several concentrations (5-50 microg/ml) of C. officinale Makino and T. bovinus extracts for 24 h inhibited angiotensin II (10(-8) M)-induced increases of [3H]thymidine uptake and cell numbers in a concentration-dependent manner. The extent of inhibitory rate of [3H]thymidine incorporation by C. officinale Makino and T. bovinus at 50 microg/ml was a similar to that by 10(-5) M of retinoic acid. Herbal extracts also conspicuously inhibited the neovascularization. In contrast to the normal branching of vascular vessels, blood vessel patterns in CAMs treated with extracts (50 microg per egg) of C. officinale Makino and T. bovinus were ran parallel to each other without much branching. Moreover, oral administration of herbal extracts (20 mg/kg per day) for 4 weeks significantly inhibited the rat corneal neovascularization induced by suture, and the length of blood vessels in herbal medicine-treated rat cornea was conspicuously lower than that in control animals. A similar inhibitory effect to these was also observed in the rat cornea treated with thalidomide (200 mg/kg per day). These findings indicate that the anti-angiogenic properties of C. officinale Makino and T. bovinus may be one of the pharmacological mechanisms underlying the anti-tumor and anti-metastatic activities of herbal extracts tested in this study.

46.Acaricidal activity of butylidenephthalide identified in Cnidium officinale rhizome against dermatophagoides farinae and dermatophagoides pteronyssinus (Acari: Pyroglyphidae).:

J Agric Food Chem. 2002 Jul 31;50(16):4479-83.
 The acaricidal activity of materials derived from the rhizome of Cnidium officinale against adults of Dermatophagoides farinae and Dermatophagoides pteronyssinus was examined using direct contact application and fumigation methods and compared with that of benzyl benzoate and N,N-diethyl-m-toluamide (DEET). The active constituent of the Cnidium rhizome was identified as butylidenephthalide by spectroscopic analyses. Responses varied with dose. On the basis of 24-h LD(50) values, the acaricidal activity of butylidenephthalide (6.77 microg/cm(2)) against D. farinae adults was comparable to that of benzyl benzoate (8.54 microg/cm(2)). Very low activity was observed with DEET (37.59 microg/cm(2)). Against D. pteronyssinus adults, butylidenephthalide (6.46 microg/cm(2)) and benzyl benzoate (6.68 microg/cm(2)) were equitoxic. DEET (17.98 microg/cm(2)) was relatively inactive. The typical poisoning symptom of butylidenephthalide was lethargy of treated mites, leading to death without knockdown, whereas benzyl benzoate and DEET caused death following uncoordinated behavior. In a fumigation test with both mite species, butylidenephthalide was much more effective in closed containers than open ones. Naturally occurring C. officinale rhizome-derived materials merit further study as potential house dust mite control agents or lead compounds.

47.Sesquiterpenes with hepatoprotective activity from Cnidium monnieri on tacrine-induced cytotoxicity in Hep G2 cells:

Planta Med. 2002 Aug;68(8):748-9.
 Bioassay-guided fractionation of the EtOH extract of Cnidium monnieri (Apiaceae) furnished two hepatoprotective sesquiterpenes, torilin (1) and torilolone (2), together with a new derivative, 1-hydroxytorilin (3). Compounds 1 and 2 showed hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC50 values of compounds 1 and 2 were 20.6 +/- 1.86 (P < 0.01) and 3.6 +/- 0.1 (P < 0.01) microM, respectively. Silybin as a positive control showed an EC50 value of 69.0 +/- 3.4 microM.

48.Acaricidal activity of Cnidium officinale rhizome-derived butylidenephthalide against Tyrophagus putrescentiae (Acari: Acaridae).:

Pest Manag Sci. 2003 Jan;59(1):119-23
 The acaricidal activity of materials derived from the rhizome of Cnidium officinale Makino against Tyrophagus putrescentiae Schrank adults was examined using direct contact application and fumigation methods, and compared with that of benzyl benzoate and N,N-diethyl-m-toluamide (DEET). The biologically active constituent of the Cnidium rhizome was identified as butylidenephthalide by spectroscopic analyses. On the basis of 24-h LD50 values, acaricidal activity was more pronounced with butylidenephthalide (5.80 microg cm(-2)) than with benzyl benzoate (9.75 microg cm(-2)) and DEET (16.26 microg cm(-2)). In typical poisoning symptoms, butylidenephthalide resulted in lethargy of treated mites, leading to death without knockdown, whereas benzyl benzoate and DEET caused death associated with uncoordinated behaviour. In a fumigation test with T. putrescentiae adults, butylidenephthalide was much more effective in closed containers than in open ones, indicating that the effects of this compound were largely due to action in the vapour phase. Naturally occurring C. officinale rhizome-derived materials merit further study as potential T. putrescentiae control agents or as lead compounds.

49.Sesquiterpenes with hepatoprotective activity from Cnidium monnieri on tacrine-induced cytotoxicity in Hep G2 cells.:

Planta Med. 2002 Aug;68(8):748-9.
 Bioassay-guided fractionation of the EtOH extract of Cnidium monnieri (Apiaceae) furnished two hepatoprotective sesquiterpenes, torilin (1) and torilolone (2), together with a new derivative, 1-hydroxytorilin (3). Compounds 1 and 2 showed hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC50 values of compounds 1 and 2 were 20.6 +/- 1.86 (P < 0.01) and 3.6 +/- 0.1 (P < 0.01) microM, respectively. Silybin as a positive control showed an EC50 value of 69.0 +/- 3.4 microM.

50.Total coumarins from fruits of Cnidium monnieri inhibit formation and differentiation of multinucleated osteoclasts of rats.:

Acta Pharmacol Sin. 2003 Feb;24(2):181-6.
 AIM: To determine the effects of TCFC (total comarins from the fruits of Cnidium monnieri) on the activity of osteoclasts in vitro. METHODS: Osteoclasts isolated from rat marrow cells were co-cultured with osteoblasts under the 1,25-dihydroxyvitamine D3. The tartrate-resistant acid phosphatase (TRAP) stain was used to identify osteoclast morphology. The activity of TRAP was measured by p-nitrophenyl sodium phosphate assay. The resorption pit area on the bone slices formed by osteoclasts was measured by computer image processing. Calcium concentration in the medium of co-culture of bone slices and osteoclasts was determined by atomic absorption spectra. RESULTS: TCFC 2.5-25 mg/L inhibited osteoclast formation and differentiation. TCFC 0.25-25 mg/L inhibited TRAP activity of osteoclasts and TCFC 25 mg/L decreased the TRAP activity by 26.3 % and 24.1 % after 48 h and 72 h, respectively. TCFC 25 mg/L decreased the osteoclastic bone resorption pit area by 25.05 % and Ca2+ release from bone slices by 41.73 %. CONCLUSION: TCFC reduced the bone lose by decreasing the osteoclast formation, its TRAP activity, and osteoclastic bone resorption.

51.Acaricidal activity of Cnidium officinale rhizome-derived butylidenephthalide against Tyrophagus putrescentiae (Acari: Acaridae).:

Pest Manag Sci. 2003 Jan;59(1):119-23.
 The acaricidal activity of materials derived from the rhizome of Cnidium officinale Makino against Tyrophagus putrescentiae Schrank adults was examined using direct contact application and fumigation methods, and compared with that of benzyl benzoate and N,N-diethyl-m-toluamide (DEET). The biologically active constituent of the Cnidium rhizome was identified as butylidenephthalide by spectroscopic analyses. On the basis of 24-h LD50 values, acaricidal activity was more pronounced with butylidenephthalide (5.80 microg cm(-2)) than with benzyl benzoate (9.75 microg cm(-2)) and DEET (16.26 microg cm(-2)). In typical poisoning symptoms, butylidenephthalide resulted in lethargy of treated mites, leading to death without knockdown, whereas benzyl benzoate and DEET caused death associated with uncoordinated behaviour. In a fumigation test with T. putrescentiae adults, butylidenephthalide was much more effective in closed containers than in open ones, indicating that the effects of this compound were largely due to action in the vapour phase. Naturally occurring C. officinale rhizome-derived materials merit further study as potential T. putrescentiae control agents or as lead compounds.

52.Effect of osthol on memory impairment of mice in AlCl3-induced acute senile model:

Yao Xue Xue Bao. 2002 Mar;37(3):178-80.
 AIM: To study the protective effect and mechanism of osthol on learning and memory impairment of mice with acute senile model induced by AlCl3. METHODS: After s.c. AlCl3 60 mg.kg-1 for 7 d and i.p. osthol 15 and 7.5 mg.kg-1 for 12 d, using step-through test and step-down test, the effect of osthol on learning and memory was observed and the glutathione peroxidase (GSH-PX) activities in blood and superoxide dismutase (SOD) activities in plasma and cerebrum were measured. RESULTS: Osthol 15 and 7.5 mg.kg-1 significantly improved the capability of memory and enhanced the activities of GSH-PX and SOD in AlCl3 treated mice. CONCLUSION: Osthol shows protective effect on brain memory impairment of mice in acute senile model induced by AlCl3. Perhaps the mechanism is involved in enhancing the activities of GSH-PX and SOD, clearing away the free radical, protecting the brain neuron from the harm of lipoperoxide.

53.Determination of chemical constituents of the essential oil from Cnidium monnieri by GC-MS:

Zhong Yao Cai. 2002 Aug;25(8):561-3.
 OBJECTIVE: The chemical components of the essential oil from Cnidium monnieri (L.) Cusson were analyzed by GC-MS. METHOD: The essential oil was extracted from Cnidium monnieri (L.) Cusson by steam distillation, the components analyzed with the different kinds of capillary columns, the optimum separated and analytical conditions were researched, the amount of the components from the essential oil were determinated by normalization method. The separated components were identified by GC-MS. RESULTS: 50 components composed of about 86% of the total essential oil were separated and identified. CONCLUSION: The method is reliable and stable.

54.Ethyl acetate soluble fraction of Cnidium officinale MAKINO inhibits neuronal cell death by reduction of excessive nitric oxide production in lipopolysaccharide-treated rat hippocampal slice cultures and microglia cells.:

J Pharmacol Sci. 2003 May;92(1):74-8.
 In the present work, we found that the ethyl acetate-soluble fraction of Cnidium officinale MAKINO (COEA) decreased nitric oxide (NO) production in the lipopolysaccharide (LPS)-stimulated BV-2 and primary microglia and suppressed expression of inducible nitric oxide synthase (iNOS) in BV-2 cells with the same pattern of NO production. In addition, we showed that excessive NO production played an important role in neuronal cell death in LPS-treated rat hippocampal slice cultures. Our data suggest that the COEA inhibits neuronal cell death by reduction of excessive NO production in LPS-treated rat hippocampal slice cultures. The ethyl acetate-soluble fraction of C. officinale reduced propidium iodide uptake and NO production in cultured media at the same time.

55.The computer image processing and cluster analysis on Fructus Cnidii from different habitats:

Zhong Yao Cai. 2003 Apr;26(4):252-4.
  To study the variation of shape of Fructus Cnidii from different habitats. METHODS: The methods of computer image processing and cluster analysis were adopted. RESULTS: The shape of Fructus Cnidii from different habitats varied significantly. CONCLUSION: According to the results of computer image processing and cluster analysis, Fructus Cnidii can be classified into three types.

56.Falcarindiol inhibits nitric oxide-mediated neuronal death in lipopolysaccharide-treated organotypic hippocampal cultures.:

Neuroreport. 2003 Oct 27;14(15):1941-4.
 Excessive nitric oxide (NO) release from activated microglia has a predominant role in neuronal death. This study investigated the effect of falcarindiol, which was isolated from Cnidium officinale Makino, on the NO-mediated neuronal death in lipopolysaccharide (LPS)-treated organotypic hippocampal cultures. Falcarindiol dose-dependently reduced inducible NO synthase (iNOS)-mediated NO production without cytotoxic effects on LPS-activated BV-2 and microglia. Predictably, falcarindiol inhibited neuronal death by reducing NO production in the LPS-treated organotypic hippocampal cultures. N-monomethyl-L-arginine (NMMA), an iNOS inhibitor, also inhibited neuronal death at 500 microM. In contrast, massive neuronal death was induced by excessive NO production in the LPS-treated alone cultures. These results suggest that excessive NO production plays an important role in the neurotoxic effect, and falcarindiol is a potential inhibitor in NO-mediated neuronal death.

57.The ameliorating effects of cognition-enhancing Chinese herbs on scopolamine- and MK-801-induced amnesia in rats.:

Am J Chin Med. 2003;31(4):543-9.
 The study was to investigate the ameliorating effects of three Chinese herbs--Achyranthes bidentata (AB), Ophiopogon japonicus (OJ) and Cnidium monnieri (CM) on scopolamine (SCOP)- and MK-801-induced amnesia by using a passive avoidance task in rats. AB, OJ and CM at 0.1 and 0.3 g/kg prolonged the step-through latency (STL) of the retention trial. In addition, AB, OJ and CM reversed the STL shortened by MK-801, but only AB reversed the STL shortened by SCOP. In conclusion, these Chinese herbs possess cognition-enhancing activities and anti-amnestic effects, but the mechanism of the effect of AB was different from those of OJ and CM.

58.Pharmacokinetics of osthole in rabbits:

Yao Xue Xue Bao. 2003 Aug;38(8):571-3.
 AIM: To investigate the pharmacokinetics of osthole in rabbits and obtain the main pharmacokinetic parameters. METHODS: A simple high-performance liquid chromatography (HPLC) method was developed to study the pharmacokinetics of osthole in rabbits by joining an internal standard (paeonal). Methanol-water (80:20) was used as the mobile phase. According to the 3P87 pharmacokinetic program, the main parameters were calculated. RESULTS: The osthole pharmacokinetics conforms to a two compartment open model after i.v. administration, T1/2 alpha = 5.81 min, T1/2 beta = 42.2 min, K21 = 0.036 0.min-1, K12 = 0.045 0.min-1, K10 = 0.054 0.min-1, AUC = 235 mg.min.L-1, CLs = 0.043 0 L.min-1.kg-1, Vc = 0.780 L.kg-1. CONCLUSION: The pharmacokinetics of osthole after i.v. administration showed a rapid distribution and elimination process in rabbits.

59.Cytotoxic activity of coumarins from the fruits of Cnidium monnieri on leukemia cell lines.:

Planta Med. 2003 Dec;69(12):1091-5.
 Cnidii monnieri Fructus [CmF; Cnidium monnieri (L.) Cusson] is used as a tonic agent in traditional Chinese medicine. In a previous Chinese herb-cytotoxicity screening test, the ethanol extract of CmF exhibited strong effects on human leukemia (HL-60), cervical carcinoma (HeLa) and colorectal carcinoma (CoLo 205) cells. Then, the CmF extract was subjected to silica gel column chromatography and recrystallization to give five coumarins: osthol, imperatorin, bergapten, isopimpinellin, and xanthotoxin. Among these compounds, osthol showed the strongest cytotoxic activity on tumor cell lines. The structure-activity relationship established from the results indicated that the prenyl group has an important role in the cytotoxic effects. However, imperatorin showed the highest sensitivity to HL-60 cells and the least cytotoxicity to normal PBMCs. Osthol and imperatorin both caused apoptotic bodies, DNA fragmentation, and enhanced PARP degradation in HL-60 cells by biochemical analysis. These results indicate that osthol and imperatorin can induce apoptosis in HL-60 cells. Therefore, osthol and imperatorin are cytotoxic marker substances in the fruits of Cnidium monnieri.

60.Preparative isolation of osthol and xanthotoxol from Common Cnidium Fruit (Chinese traditional herb) using stepwise elution by high-speed counter-current chromatography.:

J Chromatogr A. 2004 Apr 16;1033(2):373-7.
 Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of osthol and xanthotoxol from Cnidium monnieri (L.) Cusson (Common Cnidium Fruit) using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v), and (5:5:6:4, v/v), which had been selected by analytical high-speed counter-current chromatography. Using a preparative unit of the HSCCC centrifuge, about a 308 mg amount of the crude extract was separated, yielding 88.3 mg of osthol and 19.4 mg of xanthotoxol at a high purity of over 98%.

61.Osthole improves aspects of spatial performance in ovariectomized rats.:

Am J Chin Med. 2004;32(1):11-20.
 The present study was designed to investigate the ameliorating effects of Cnidiuim monnieri L. Cusson (CM) and osthole, a constituent of CM, on the spatial performance deficit in scopolamine (SCOP)-treated or ovariectomized (OVA) rats. CM improved the deficit of spatial performance, and reversed the lower plasma estradiol levels caused by SCOP in female rats. In addition, osthole (3 and 10 mg/kg, s.c.) improved the performance deficit in OVA rats. It (10 and 30 micrograms/brain, icv) also improved the performance deficit caused by SCOP in intact female rats, and at 30 micrograms/brain improved the deficit in OVA rats. However, osthole did not alter the latency swum to reach the visible target in SCOP-treated and OVA rats. Accordingly, we suggested that osthole is an active constituent of CM, and possesses ameliorating effects on the spatial performance deficits in SCOP-treated female rats or OVA rats. The action mechanism of the effects of osthole on performance deficits was related to the estrogen-like properties and activating the central cholinergic neuronal system.

62.Antioxidative effects related to the potential anti-aging properties of the Chinese prescription Kangen-karyu and Carthami Flos in senescence-accelerated mice.:

Arch Gerontol Geriatr. 2004 Jul-Aug;39(1):69-82.
 The popular oxidative stress theory predicts that enhancement of the antioxidative defense system to attenuate free radical-induced damage counteracts the aging process. We used senescence-accelerated mice (SAM) because SAM has been shown to suppress the antioxidative defense system and mitochondrial dysfunction induced by oxidative stress. We investigated the antioxidative effects of the Chinese prescription Kangen-karyu and its crude drug component Carthami Flos. The administration of Kangen-karyu extract at 100 mg/kg body weight per day for 10 weeks inhibited generation of nitric oxide, superoxide and the hydroxyl radical (*OH), while Carthami Flos extract showed only *OH-scavenging activity. Diet supplemented with Kangen-karyu and Carthami Flos extracts enhanced the activities of the antioxidative enzymes superoxide dismutase in hepatic tissue and glutathione peroxidase in renal tissue, and reduced the hepatic lipid peroxidation level which increased with aging, indicating the protective action against oxidative stress by enhancing the antioxidative status. Hepatic and renal dysfunction with aging was also ameliorated by the administration of Kangen-karyu and Carthami Flos supplements. Furthermore, the observed antioxidative properties of the Chinese prescription Kangen-karyu were more evident than those of Carthami Flos. These findings suggest that the protective activity of Kangen-karyu against the oxidative tissue damages during aging may be due partly to synergistic and/or additive effects of its crude preparation. The present study strongly indicates that Kangen-karyu counteract the oxidative stress and ameliorating tissue damage possibly associated with aging in SAM.

63.Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test.:

J Pharmacol Sci. 2004 Sep;96(1):33-41. Epub 2004 Sep 4.
 The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-beta-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol.

64.Coumarins from Cnidium monnieri (L.) and their proliferation stimulating activity on osteoblast-like UMR106 cells.:

Pharmazie. 2004 Aug;59(8):643-5.
 The proliferation of various fractions of alcoholic extracts from fruits of Cnidium monnieri (L.) Cuss (umbelifera) were screened using the osteoblast-like UMR106 cells in vitro. The chloroform fraction from the crude extract was found to have the most stimulating activity. Three coumarins (osthole, bergapten and imperatorin) were isolated from this fraction by activity-guided assay, and their effects on osteoblastic proliferation were investigated. Osthole, a major pharmacologically active constituent, significantly promoted the cells' activity. Bergapten and imperatorin were less effective than osthole. These results suggested Cnidium monnieri (L.) Cuss extracts might have potential activity against osteoporosis, and its chloroform fraction might contain active constituents stimulating osteoblasts.

65.Analysis on intraspecific variation of Cnidium monnieri by RAPD:

Zhong Yao Cai. 2004 Jul;27(7):469-71.
 OBJECTIVE: To study the genetic variation of Cnidium monnieri from different regions. METHODS: Random amplified polymophic DNA technique was used to analyze genetic polymorphy of Cnidium monnieri from 9 different regions, and dendrogram was constructed by UPGMA. RESULTS: 20 random primers were used for polymorphic selection. A total of 75 bands were amplified, 64 of which were polymorphism. CONCLUSION: The smaller the geographic distances between two Cnidium monnieri, the smaller genetic differences. However, it should not be overlooked that natural environment, especially the local ecological conditions may also show some influences on the genetic variations among different C. monnieri samples.

66.Effects of osthol on androgen level and nitric oxide synthase activity in castrate rats:

Zhong Yao Cai. 2004 Jul;27(7):504-6.
 OBJECTIVE: To investigate the effects of osthol on androgen level and nitric oxide synthase (NOS) activity in castrate rats. METHODS: Immature castrate male rats were treated with osthol daily for 20 d. The levels of testosterone(T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in serum and the activity of NOS, the nitric monoxide (NO) level in penis tissue were determined. RESULTS: T( P < 0.05), LH( P < 0.05) and FSH( P < 0.01) were significantly increased at the high dose of osthol treatment. The high and low dose of osthol treatment significantly enhanced the activity of NOS (P < 0.01). CONCLUSION: Osthol could increase androgen, gonadotropin and nitric oxide synthase (NOS) activity. It suggested that osthol had androgen-like effect and gonadotropin-like effect.

67.Preparative isolation and purification of coumarins from Cnidium monnieri (L.) Cusson by high-speed counter-current chromatography.:

J Chromatogr A. 2004 Nov 5;1055(1-2):71-6.
 A high-speed counter-current chromatography (HSCCC) method for separation and purification of coumarins from Cnidium monnieri (L.) Cusson was developed by using stepwise elution with a pair of two-phase solvent system composed of light petroleum-ethyl acetate-methanol-water at volume ratios of 5:5:5:5, 5:5:6:4 and 5:5:6.5:3.5. Five kinds of coumarins were obtained and yielded 7.6 mg of xanthotoxin(I), 7.6 mg of isopimpinellin(II), 9.7 mg of bergapten(III), 60.5 mg of imperatorin(IV), 50.6 mg of osthole(V) and 10.2 mg of one unknown compound from 150mg crude sample. The purity of these compounds was 95.0%, 99.6%, 99.7%, 100%, 100% and 98.1%, respectively, as determined by HPLC. Their structures were identified by 1H NMR.

68.Preparative isolation and purification of bergapten and imperatorin from the medicinal plant Cnidium monnieri using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase.:

J Chromatogr A. 2004 Dec 17;1061(1):51-4.
 A high-speed counter-current chromatography (HSCCC) method was developed for the preparative separation and purification of bergapten and imperatorin from the Chinese medicinal plant Cnidium monnieri (L.) Cusson. The crude extract was obtained by extraction with ethanol from the dried fruits of Cnidium monnieri (L.) Cusson under sonication. Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (5:5:5:5, v/v/v/v) was successfully performed by increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml min(-1) after 180 min. The components purified and collected were analyzed by high-performance liquid chromatography. The method yielded 45.8 mg of bergapten at 96.5% purity and 118.3 mg of imperatorin at 98.2% purity from 500 mg of the crude extract in a single run. The recoveries of bergapten and imperatorin were 92.1 and 93.7%, respectively.

69.Development of high-performance liquid chromatographic fingerprints for distinguishing Chinese Angelica from related umbelliferae herbs.:

J Chromatogr A. 2005 May 6;1073(1-2):383-92.
 A high-performance liquid chromatographic (HPLC) fingerprint of Chinese Angelica (CA) was developed basing on the consistent chromatograms of 40 CA samples (Angelica sinensis (Oliv.) Diels). The unique properties of this HPLC fingerprints were validated by analyzing 13 related herbs including 4 Japanese Angelicae Root samples (JA, A. acutiloba Kitagawa and A. acutiloba Kitagawa var. sugiyame Hikino), 6 Szechwan Lovage Rhizome samples (SL, Ligusticum chuanxiong Hort.) and 3 Cnidium Rhizome samples (CR, Cnidium officinale Makino). Both correlation coefficients of similarity in chromatograms and relative peak areas of characteristic compounds were calculated for quantitative expression of the HPLC fingerprints. The amount of senkyunolide A in CA was less than 30-fold of that in SL and CR samples, which was used as a chemical marker to distinguish them. JA was easily distinguished from CA, SL and CR based on either chromatographic patterns or the amount of coniferyl ferulate. No obvious difference between SL and CR chromatograms except the relative amount of some compounds, suggesting that SL and CR might have very close relationship in terms of chemotaxonomy. Ferulic acid and Z-ligustilide were unequivocally determined whilst senkyunolide I, senkyunolide H, coniferyl ferulate, senkyunolide A, butylphthalide, E-ligustilide, E-butylidenephthalide, Z-butylidenephthalide and levistolide A were tentatively identified in chromatograms based on their atmospheric pressure chemical ionization (APCI) MS data and the comparison of their UV spectra with those published in literatures.

70.Larvicidal and adulticidal activity of alkylphthalide derivatives from rhizome of Cnidium officinale against Drosophila melanogaster.:

J Agric Food Chem. 2005 Jul 13;53(14):5549-53.
 The insecticidal activity of the chloroform extract of Cnidium officinale rhizomes and its constituents was investigated against larvae and adults of Drosophila melanogaster and compared with that of rotenone. Bioassay-guided isolation of the chloroform extract of C. officinale resulted in the isolation and characterization of four alkylphthalides, cnidilide (1), (Z)-ligustilide (2), (3S)-butylphthalide (3), and neocnidilide (4). The structures of these compounds were established by spectroscopic analysis. The isolated compounds 2, 3, and 4 exhibited LC50 values of 2.54, 4.99, and 9.90 micromol/mL of diet concentration against larvae of D. melanogaster, respectively. Against both sexes (males/females, 1:1) of adults (5-7 days old), compound 3 showed the most potent activity of the compounds isolated with the LD50 value of 5.93 microg/adult, comparable to that of rotenone (LD50 = 3.68 microg/adult). Structure-activity relationships of phthalides isolated suggest that the presence of conjugation with the carbonyl group in the lactone ring appeared to play an important role in the larvicidal activity. Acetylcholinesterase (prepared from the adult heads of D. melanogaster) inhibitory activity was also investigated in vitro to determine the insecticide mode of action for the acute adulticidal activity.

71.Study on extraction of coumarins in Cnidium monieri by supercritical CO2 and separation of compositions analysis:

Zhongguo Zhong Yao Za Zhi. 2005 Jul;30(14):1080-2.
 OBJECTIVE: To analyze the chemical constituents of supercritical carbon dioxide extraction products from Cnidium monieri. METHOD: Four-factor and three-level orthogonal experimental design was used to optimize the SFE conditions as guided by the content of total coumarins in the extract. The chemical constituents were separated and identified by recrystalization. RESULT: Optimum extraction process was established: 25 MPa as extraction pressure, 50 degrees C as extraction temperature, 6.5 MPa as separation pressure and 60 degrees C as separation temperature. CONCLUSION: Changes in extraction pressure, temperature, time, pulverized degree and separation pressure affect the extracting results remarkably. The two kinds of chemical constituents were separated by recrystallization from C. monieri and identified by the methods of UV, IR, MS, NMR.

72.Inhibitory effects of Cnidium officinale Makino and Tabanus fulvus Meigan on the high glucose-induced proliferation of glomerular mesangial cells.:

Phytomedicine. 2005 Sep;12(9):648-55.
 This study describes a potent activity of Cnidium officinale Makino (Cnidii rhizoma) and Tabanus fulvus Meigan (Tabanus) as an inhibitor of high glucose-induced proliferation of glomerular mesangial cells (GMCs). Raising the ambient glucose concentration from 5.6 to 25 mM for 24 h caused a dramatic increase in [3H]thymidine incorporation, and these increases were attenuated by treatment of GMCs with the extracts of Cnidii rhizoma and Tabanus (2.5-20 microg/ml) in a dose-dependent manner. In contrast, extracts of Cnidii rhizoma or Tabanus (20 microg/ml) did not change the growth of GMCs cultured under normal glucose condition. To clarify the mechanism involved in anti-proliferative activity of these medicines, this study examined the effects of Cnidii rhizoma and Tabanus on high glucose-stimulated extracellular matrix (ECM) protein accumulation and transforming growth factor-beta1 (TGF-beta1) production. Exposure of GMCs to high glucose significantly stimulated the ECM protein, collagen and fibronectin, accumulation and TGF-beta1 secretion, and these changes were dramatically diminished by treatment of GMCs with extracts of Cnidii rhizoma or Tabanus (10 microg/ml). Taken together, these results indicate that Cnidii rhizoma and Tabanus inhibit the high glucose-induced GMC proliferation partially through suppressing the ECM accumulation and TGF-beta1 production, suggesting that these medicines may be a promising agent for treating the development and progression of diabetic glomerulopathy.

73.Progress in study of chemical constituents and anti-tumor activities of Cnidium monnieri:

Zhongguo Zhong Yao Za Zhi. 2005 Sep;30(17):1309-13.
 The main pharmacological constituents of Chinese traditional medicine herb Cnidium monnieri are coumarin compounds and volatile oil. In addition, it contains monoterpene polyols, glucides, as well as recently discovered sesquiterpene components. In recent years, rather active investigations of its anti-tumor were performed at home and abroad. C. monnieri possesses multi-aspect and comprehensive anti-tumor functions, involving directly tumor-inhibitory activity, anti-mutagenicity, reversing multi-drug tolerance of tumor, as well as improving immune functions and so on. In this review, chemical constituents, anti-tumor activities and relevant investigations of Fructus Cnidii were summarized recent decade.

74.Determination of five coumarins in Cnidii Fructus by micellar electrokinetic capillary chromatography.:

Planta Med. 2005 Dec;71(12):1152-6.
 A micellar electrokinetic capillary chromatography (MEKC) method for the separation and quantification of the coumarins in Cnidii Fructus was developed for the first time. Within 25 minutes, 5 major coumarins were separated using 18 mM borate, 12 mM phosphate and 50 mM SDS (pH 9.2) containing 20 % methanol. The relative standard deviations of migration times and peak areas were less than 5 %. The total contents of the five coumarins in plants from different habitats ranged from 13.6 to 44.6 mg/g, and recoveries ranged from 96.0 to 102.8 %. The effects of buffer concentration, SDS, pH value and organic modifier on the separation were investigated.

75.Comparison of micellar electrokinetic capillary chromatography and high performance liquid chromatography on fingerprint of Cnidium monnieri.:

Chem Pharm Bull.2006 Jun;54(6):897-901.
 In our studies, micellar electrokinetic capillary chromatography (MEKC) was employed in fingerprint analysis of Cnidium monnieri for the first time. Average chromatography of 10 batches Cnidium monnieri from Jiangsu province, China, which have long been considered as the original and genuine herbal medicine, was first established as the characteristic fingerprint. Within 25 min the major effective components were separated by 18 mM borate, 12 mM phosphate and 50 mM SDS (pH 9.2) containing 20% methanol. The relative standard deviations of migration times and peak areas were less than 5%. As a new approach of fingerprint, MKCE was compared to the conventional approach-HPLC in our experiments. The fingerprint developed by HPLC comprised 8 peaks that were collected within 40 min. Relative standard deviation (RSD) values of retention times of corresponding peaks in HPLC analysis were very small (maximum 3% and average 0.9%). In conclusion, each two methods had its advantages and disadvantages. Furthermore, besides HPLC, MEKC as a feasible method, could be used in the development of fingerprint of Cnidium monnieri.

76.Inhibitory effects of natural plant extracts on Verticillium albo-atrum:

Ying Yong Sheng Tai Xue Bao. 2006 Jun;17(6):1137-40.
 This paper studied the inhibitory effects of 54 kinds of ethanol-extracted plant solutions on Verticillium albo-atrum. The results showed that 15 kinds of these extracts could inhibit the growth of verticillium albo-atrum mycelium, with an inhibitory rate more than 50%, among which, the inhibitory rate of Asarum sieboldii, Coptis chinensis, Magnolia officinalis, Acacia catechu, Sophora flavescens, Glycyrrhiza uralensis, Cnidium monnieri, Platycodon grandiflorum and Allium. cepa. extracts was higher than 65%, and that of Cnidium monnieri extract reached 86.84%. A total of 16 kinds of plant extracts decreased the spore germination of V. albo-atrum, with the inhibitory rate higher than 70%, and there were 7 kinds of plant extracts whose inhibitory rate reached 95%. Almost no spore bourgeon was found after treated with Asarum sieboldii, Coptis chinensis, and Magnolia officinalis extracts. The extract of Acacia catechu did not inhibit the growth of mycelium, but restrained the spore germination by 100%. Cnidium monnieri extract could strongly inhibit the growth of mycelium, but had a less effect on spore germination rate (only by 11.3%). The active substances found in natural plant extracts which had the inhibitory effects on pathogen brought us a new and promising method to deal with V. albo-atrum and other vegetable diseases.

77.Fingerprint analysis of the fruits of Cnidium monnieri extract by high-performance liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry.:

J Pharm Biomed Anal. 2007 Feb 19;43(3):926-36. Epub 2006 Oct 13.
 A method incorporating high-performance liquid chromatography (HPLC) with electrospray ionization (ESI) and tandem mass spectrometry (MS), with parallel analysis by HPLC with UV detection using a diode-array detector (DAD) was developed for the qualitative characterization of coumarin and chromone constituents in the fruits of Cnidium monnieri. The chromatographic separations were performed on a Diamonsil C18 column (4.6 mm x 200 mm, 5 microm) with water with 50 mM ammonium acetate and 2% acetic acid (A) and acetonitrile (B) as the mobile phase. According to the characteristic UV spectra, the information of molecular weight and structure provided by ESI-MS/MS, 13 coumarin and 7 chromone components were detected and identified. This method is rapid and reliable for identification of the constituents in the complex herbal system, and the fragmentation patterns proposed could be extended to the similar compounds.

78.Antitumor effects of Osthol from Cnidium monnieri: an in vitro and in vivo study.:

Phytother Res. 2007 Mar;21(3):226-30.
 Cnidium monnieri (L.) Cusson is a Chinese medicine which is used widely by traditional medicine doctors. Osthol is a major bio-activity compound of the herb. In this study, osthol was isolated from C. monnieri and its in vitro and in vivo antitumor effects studied. The results of the in vitro study showed: that osthol inhibited the growth of HeLa, in a time- and concentration-dependent manner, with IC(50) values of 77.96 and 64.94 microm for 24 and 48 h, respectively; that osthol had lower cytotoxic effects in primary cultured normal cervical fibroblasts; and that increased DNA fragmentation and activated PARP in HeLa after treatment with osthol which could induce apoptosis. The results of the in vivo model showed that the survival days of the P-388 D1 tumor-bearing CDF(1) mice were prolonged (ILS% = 37) after osthol (30 mg/kg) was given once a day for 9 days. Based on these results, it is suggested that osthol could inhibit P-388 D1 cells in vivo and induce apoptosis in HeLa cells in vitro, and that osthol is good lead compound for developing antitumor drugs. However, C. formosanum Yabe of Taiwan's endemic plants contained little osthol, with no imperatorin, and its major components were different from that of C. monnieri. Therefore, it is suggested that C. formosanum also may possess economic worth.

79.Therapeutic effect of osthole on hyperlipidemic fatty liver in rats.:

Acta Pharmacol Sin. 2007 Mar;28(3):398-403.
 AIM: To study the effects of osthole on hyperlipidemic fatty liver and investigate the possible mechanisms. METHODS: A rat model with hyperlipidemic fatty liver was successfully established by feeding fatty milk for 6 weeks. The experimental rats were then treated with 5-20 mg/kg osthole for 6 weeks. The mouse hyperlipidemic model was induced by feeding fatty milk when they were treated with 10-20 mg/kg osthole for 3 weeks. RESULTS: After treatment with osthole, the levels of rat serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol significantly decreased as compared with the fatty liver model group (P< 0.05 or P< 0.01). Hepatic weight and its coefficient, the hepatic tissue contents of TC, TG, and malondialdehyde, also significantly decreased (P< 0.05 or P< 0.01). In fatty milk-induced hyperlipidemic mice, the post-heparin plasma activities of lipoprotein lipase (LPL), hepatic lipase (HL), and total lipase (TL) significantly increased after treatment with 10-20 mg/kg osthole for 3 weeks (P< 0.05 or P< 0.01). Importantly, the histological evaluation of rat liver demonstrated that osthole dramatically decreased lipid accumulation (P< 0.01). CONCLUSION: Osthole was found to have therapeutic effects on fatty milk-induced rat fatty liver; the mechanisms might be associated with its anti-oxidation and the elevation of the activities of LPL and HL.

80.Coumarins from Cnidium monnieri and their antiosteoporotic activity.:

Planta Med. 2007 Jan;73(1):13-9.
 Bioactivity-guided fractionation has led to the successful isolation of antiosteoporotic components, i. e., osthole, imperatorin and bergapten from an ethanolic extract of the fruits of Cnidium monnieri (L.) Cusson. Among them, osthole was determined as the major compound possessing antiosteoporotic activity. Further study showed that osthole not only promoted the proliferation and activity of alkaline phosphatase of osteoblasts in neonatal calvaria cultures, but also inhibited the bone resorption by decreasing the formation, differentiation and TRAP activity of osteoclasts derived from rat marrow cells.

81.Effects of osthol on blood pressure and lipid metabolism in stroke-prone spontaneously hypertensive rats.:

J Ethnopharmacol. 2007 May 30;112(1):26-31. Epub 2007 Feb 1.
 Osthol, a coumarin compound, was isolated from the dried fruits of Cnidium monnieri (Umbelliferae) and the effect of dietary osthol on hypertension and lipid metabolism was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were fed the experimental diet containing 0.05% osthol by weight for 4 weeks with free access to the diet and water. Elevation of systolic blood pressure was significantly suppressed on and after 3 weeks. In addition, significant decreases in cholesterol and triglyceride contents in the liver were recognized without any significant changes in serum lipids profiles. A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids. This may be responsible, at least in part, for the reduction of hepatic triglyceride content in SHRSP. These beneficial effects of osthol could be useful for both prevention of atherosclerosis and suppression of hepatic lipid accumulation.

82.Analysis of coumarins in Fructus Cnidii by HPLC-ESI-MS:

Zhong Yao Cai. 2006 Oct;29(10):1033-5.
 OBJECTIVE: To analyze coumarins in Fructus Cnidii by HPLC-ESI-MS. METHODS: Coumarins in Fructus Cnidii were subjected to HPLC, using Shim-pack CLC-ODS column, methanol-water (70:30) as mobile phase, and 254 nm as DAD wavelength. A quadrupole mass spectrometer was applied to verify the LC elute, operated in the positive ion mode. RESULTS: Three coumarins were determined and the possible structures of seven coumarins were deduced based on the chromatography and MS data. CONCLUSION: The application of this method could be available for the rapid identification of constituents from traditional Chinese medicines.

83.Osthole improves fat milk-induced fatty liver in rats: modulation of hepatic PPAR-alpha/gamma-mediated lipogenic gene expression.:

Planta Med. 2007 Jul;73(8):718-24. Epub 2007 Jul 5.
 The objectives of this study were to determine the therapeutic effect of osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), in hyperlipidemic fatty liver (HFL) rats and investigate the possible mechanism of the osthole treatment. The HFL rat model was established by feeding Sprague-Dawley rats with fat milk for 6 weeks. The experimental rats were then treated with a dose of osthole of 5 - 20 mg/kg for 6 weeks. After the treatment, total cholesterol (TC) and triglycerides (TG) in serum and hepatic tissue, as well as the coefficient of hepatic weight were measured. The results showed that the TC and TG in both serum and hepatic tissue and the coefficient of hepatic weight in the osthole-treated rats were lower as compared to those in the experimental group, respectively (P < 0.05 or P < 0.01). Moreover, as compared to the control group, the osthole treatment increased the PPARalpha/gamma mRNA expression by 58.0 - 84.0 % and 20.4 - 77.4 %, respectively. The related target genes for mRNA expression were also increased by osthole-treatment, e. g., 53.4 - 93.2 % for CYP7A, 21.1 - 63.2 % for L-FABP and 34.1 - 57.3 % for FATP4, while the DGAT mRNA expression was decreased by 26.0 - 44.4 %. The therapeutic effect of osthole was further confirmed by histological evaluation of the liver showing a dramatically decreased lipid accumulation and improved ultrastructure of hepatocytes. In conclusion, osthole exerts therapeutic effects on fat milk-induced fatty liver in rats, by regulating mRNA expression of the target genes of CYP7A, DGAT, L-FABP and FATP4 via increasing the PPARalpha/gamma mRNA expression.

84.Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM.:

Phytother Res. 2008 Jan;22(1):36-42.
 The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans.

85.Chromatographic fingerprint of Cnidium monnieri:

Yao Xue Xue Bao. 2007 Aug;42(8):877-81.
 To establish the method of HPLC-fingerprint analysis for the quality control of Cnidium monnieri L. Cuss., and identify its active constituents by HPLC-MS, 35 batches of samples were analyzed on a Shimadzu C18 column with a gradient of acetonitrile and 0.1% aqueous aceticacid at a flow rate of 1.0 mL x min(-1) and detected at 245 nm and 322 nm. Furthermore, the typical samples were detected by HPLC-DAD-MS under negative ion mode. 35 batches of Cnidium monnieri L. Cuss. samples were classified into four types based on the results of similarity analysis. According to the comparison of the t(R), MS data and UV maximum absorbance (lambda(max)) values with the standards, 8, 7, 4 and 2 coumarins components were identified in four types of Cnidium monnieri L. Cuss. extracts, separately. The method is repeatable and reliable, and it is capable of effectively controlling the quality of Cnidium monnieri L.

86.Simultaneous determination of 5 active components in Fructus Cnidii by HPLC:

Zhongguo Zhong Yao Za Zhi. 2007 Sep;32(18):1883-5.
 OBJECTIVE: To develop an RP-HPLC method for simultaneous determination of 5 constituents in Fructus Cnidii. METHOD: Analysis was performed on an Alltech C18 (4.6 mm x 250 mm, 5 microm) column. The mobile phases were acetonitrile water and acetic acid with gradient elution. The flow rate was 1 mL x min(-1). The monitoring wavelength was 325 nm and 245 nm. The column temperature was 40 degrees C. RESULT: The linear response ranges were 1-20 microg x mL(-1) (r = 0.999 9) for xanthotoxin, 1-20 microg x mL(-1) (r = 0.999 9) for isopimpinellin, 11-20 microg x mL(-1) (r = 0.999 8) for bergapten, 100-1 200 microg x mL(-1) (r = 0.999 7) for imperatorin, 100-2 000 microg x mL(-1) (r = 0.999 9) for osthole. The average recoveries were all above 95%. CONCLUSION: The method is simple, sensitive and accurate with good reproducibility.

87.Inhibitory effect of osthole on alcohol-induced fatty liver in mice.:

Dig Liver Dis. 2009 Feb;41(2):127-33. Epub 2008 Mar 12.
 BACKGROUND: Alcohol is a major cause of fatty liver, the disease is a spectrum that is initiated with steatosis, and without therapy it is apt to develop inflammation, necrosis, fibrosis and finally cirrhosis. There are currently no ideal pharmacological reagents that can prevent or reverse this disease. Osthole is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a Chinese herbal medicine, which has been used in clinics for many years. It has many functions such as anti-inflammation, anti-osteoporosis and anti-tumor and so on, but there is no report about treatment of alcoholic fatty liver in mice. AIM: To examine the inhibitory effect of osthole on alcohol-induced fatty liver in mice and to investigate the potential mechanisms. METHODS: A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthole 10, 20, 40 mg/kg for 4 weeks. Whereafter, the lipids in serum and hepatic tissue, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione hormone (GSH), tumor necrosis factor-alpha (TNF-alpha) in hepatic tissue, hepatic weight coefficient and its histological evaluation were measured. RESULTS: After treatment with osthole, the levels of serum total cholesterol (TC), triglyceride (TG), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased, the levels of MDA and TNF-alpha in liver were also decreased, while the GSH in liver was increased. Importantly, the histological evaluation of liver specimens demonstrated that osthole dramatically decreased lipid accumulation. CONCLUSION: Osthole could inhibit alcohol-induced fatty liver in mice, and the mechanism might be associated with its anti-oxidation and suppression of TNF-alpha production.

88.Petroleum ether extract of Cnidium monnieri ameliorated scopolamine-induced amnesia through adrenal gland-mediated mechanism in male rats.:

J Ethnopharmacol. 2008 May 22;117(3):403-7. Epub 2008 Feb 19.
 AIM: Our previous study indicated petroleum ether layer of Cnidium monnieri L. Cuss. (CM) and its ingredient osthole could alleviate scopolamine-induced amnesia in female rats. MATERIALS AND METHODS: Hence, this study was desired to investigate the mechanism of the ameliorating effects of petroleum ether layer of CM on the performance impairment of inhibitory avoidance task and Morris water maze induced by scopolamine in male rats. RESULTS: CM at 0.1-0.6g/kg orally administered 60 min before the training trial ameliorated the scopolamine-induced performance impairment on inhibitory avoidance learning and water maze in male rats. Only adrenalectomy but not peripheral cholinergic antagonist scopolamine methylbromide and catecholaminergic neurotoxin 6-hydroxydopamine blocked the ameliorating effects of CM on scopolamine-induced performance impairment in rats. CONCLUSION: Therefore, we demonstrated that the ameliorating effects of CM on scopolamine-induced performance impairment may be related to activating the adrenal gland and central acetylcholingeric neuron, instead of peripheral nervous system.

89.Micelle-mediated extraction and cloud-point preconcentration of osthole and imperatorin from Cnidium monnieri with analysis by high performance liquid chromatography.:

J Chromatogr A. 2008 Jul 25;1200(2):93-9. Epub 2008 May 3.
 A new method based on micelle-mediated extraction and cloud-point preconcentration was developed for the separation and determination of hydrophobic compounds osthole and imperatorin from Cnidium monnieri by high performance liquid chromatography with photodiode array detection. The non-ionic surfactant C(13)E(8) (Genapol X-080) was chosen as the extract solvent. Various experimental conditions were investigated to evaluate and optimize the extraction and preconcentration process. The chromatographic separation was accomplished on a Zorbax SB-C(18) analytical column (150 mm x 4.6mm i.d., 5 microm particle diameter) maintained at 30 degrees C and detected by UV absorption at 320 nm. The gradient elution was achieved with a mobile phase composed of 0.1% phosphoric acid and acetonitrile at a flow rate of 1.0 mL min(-1). Under the optimum conditions, the calibration curve for both analytes was linear in the range of 0.52-33.5 microg mL(-1) with the correlation coefficients greater than 0.9996. The intra-day and inter-day precision (RSD) is below 5.3% and the limits of detection (LOD) for the analytes are 93 and 124 ng mL(-1)(S/N=3). The proposed technique is a low cost, simple and sensitive method with high clean-up effect. Finally, the method was successfully applied to separate and determine osthole and imperatorin from C. monnieri, respectively.

90.Osthole regulates enzyme protein expression of CYP7A1 and DGAT2 via activation of PPARalpha/gamma in fat milk-induced fatty liver rats.:

J Asian Nat Prod Res. 2008 Jul-Aug;10(7-8):807-12.
 Osthole (1), an active constituent isolated from Cnidium monnieri (L.) Cusson, has been used in the treatment of diseases for many years in clinical. The aim of this present study was to determine the effect of 1 on protein expression of PPARalpha/gamma and related target molecules such as CYP7A and DGAT protein expression in the liver of hyperlipidemic fatty liver (HFL) rats, and to investigate the possible mechanism of treating HFL.

91.Osthole and imperatorin, the active constituents of Cnidium monnieri (L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals.:

Neurochem Int. 2008 Dec;53(6-8):416-23. Epub 2008 Oct 1.
 We examined the effects of osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, on the release of glutamate from rat hippocampal synaptosomes and investigated the possible mechanism. The results showed that osthole or imperatorin significantly facilitated 4-aminopridine (4-AP)-evoked glutamate release in a concentration-dependent manner. The facilitatory action of osthole or imperatorin was blocked by the vesicular transporter inhibitor bafilomycin A1, not by the glutamate transporter inhibitor l-transpyrrolidine-2,4-dicarboxylic acid (l-trans-PDC), indicating that the release facilitation by osthole or imperatorin results from a enhancement of vesicular exocytosis and not from an increase of Ca(2+)-independent efflux via glutamate transporter. Examination of the effect of osthole and imperatorin on cytosolic [Ca(2+)] revealed that the facilitation of glutamate release could be attributed to an increase in voltage-dependent Ca(2+) influx. Consistent with this, omega-conotoxin MVIIC, a wide-spectrum blocker of the N- and P/Q-type Ca(2+) channels, significantly suppressed the osthole or imperatorin-mediated facilitation of glutamate release, but intracellular Ca(2+) release inhibitor dantrolene had no effect. Osthole or imperatorin did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization; thus, the facilitation of 4-AP-evoked Ca(2+) influx and glutamate release produced by osthole or imperatorin was not due to it decreasing synaptosomal excitability. In addition, osthole or imperatorin-mediated inhibition of 4-AP-evoked release was prevented by protein kinase C (PKC) inhibitors. Furthermore, osthole or imperatorin increased 4-AP-induced phosphorylation of PKC. Together, these results suggest that osthole or imperatorin effects a facilitation of glutamate release from nerve terminals by positively modulating N-and P/Q-type Ca(2+) channel activation through a signaling cascade involving PKC.

92.Analysis of Cnidium monnieri fruits in different regions of China.:

Talanta. 2001 Mar 16;53(6):1155-62.
 Application of multivariate data analysis has become a popular method in the last decades, mainly because it can provide information not otherwise accessible. The information includes classification, searching similarities, finding relationships, finding physical significance to principal components, etc. Fifty three Chinese medicinal herbs of eleven kinds of coumarins were collected and determined by HPLC. The results were studied by principal component analysis (PCA) and cluster analysis. It was showed that the samples could be clustered reasonably into different groups, which correspond with variation of regularity and distribution of coumarin of Cnidium monnieri fruits in different regions of China.

93.Effect of the Chinese herb extract osthol on IL-4-induced eotaxin expression in BEAS-2B cells.:

Pediatr Neonatol. 2008 Aug;49(4):135-40.
 Asthma is an allergic inflammatory disease of the airways. The interaction between bronchial epithelial cells and eosinophils is an important feature of an asthma attack. Eotaxin, an eosinophil-specific C-C chemokine, is a potent chemoattractant involved in the mobilization of eosinophils into the airway after allergic stimulation. Cnidii monnieri fructus, the dried fruit of Cnidium monnieri Cusson, has been used as an antipruritogenic agent in ancient China. OsthoL is the major component of Cnidii monnieri fructus extract. We investigated the ability of osthol to regulate cytokine-induced eotaxin expression in the human bronchial epithelial cell line BEAS-2B. METHODS: BEAS-2B cells were pretreated with osthol at different concentrations (0.1-10 microM), and then stimulated with interleukin (IL)-4 alone, or in combination with tumor necrosis factor (TNF)-alpha. Eotaxin levels were determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. STAT6 (signal transducer and activator of transcription 6) and MAPK (mitogen-activated protein kinase) expressions were evaluated by Western blotting, to detect possible intracellular signal transduction. RESULTS: IL-4 and TNF-alpha significantly induced eotaxin expression in BEAS-2B cells. Expression of eotaxin was suppressed by osthol (0.1-10 microM) in a dose-dependent manner. Osthol did not suppress IL-4-induced p38, ERK or JNK expression. Osthol did suppress IL-4-induced STAT6 in a dose-dependent manner. CONCLUSION: Osthol suppressed IL-4-induced eotaxin in BEAS-2B cells via inhibition of STAT6 expression. This data suggest that osthol might have potential for treating allergic airway inflammation.

94.Identification and quantification of the volatile constituents in Cnidium monnieri using supercritical fluid extraction followed by GC-MS.:

J Sep Sci. 2009 Jan;32(2):252-7.
 The volatile components of Cnidium monnieri were obtained by supercritical fluid extraction (SFE) and analyzed by GC-MS (identification and determination of metabolites). The compounds were identified according to their retention times and mass spectra. The effects of different parameters, such as extraction pressure, temperature, dynamic extraction time, flow rate of CO(2), on the SFE of C. monnieri extracts were investigated. A total of 14 compounds of SFE extracts were identified. Osthole (69.52%), bornyl acetate (10.03%), alpha-pinene (4.71%), and imperatorin (2.42%) were the major compounds identified in C. monnieri SFE extracts. The quantitation of osthole and imperatorin were then accomplished. The linear calibration ranges were all 5-1000 microg/mL for osthole and imperatorin by GC-MS analysis. The recovery of osthole and imperatorin were in the range 96.5-101.8%. The LODs for osthole and imperatorin were 1.0 and 0.6 microg/mL, respectively.

95.Protective effect of the extracts from Cnidium officinale against oxidative damage induced by hydrogen peroxide via antioxidant effect.:

Food Chem Toxicol. 2009 Mar;47(3):525-9. Epub 2008 Dec 7.
 The dried rhizomes of Cnidium officinale are used as herbal drugs in the treatment of pain, inflammation, menstrual disturbance and antivitamin deficiency disease, and also act as a blood pressure depressant. In addition, there are several reports suggesting that they have pharmacological properties to tumor metastasis and angiogenesis, and that they act as an inhibitor of high glucose-induced proliferation of glomerular mesangial cells. However, little has been known about the functional role of the extracts from C. officinale on oxidative DNA damage and apoptosis caused by ROS. In this work, we have investigated the DPPH radical, hydroxyl radical and intracellular ROS scavenging capacity, and Fe(2+) chelating activity of the extracts from C. officinale. In addition, we evaluated whether the extracts are capable of reducing H(2)O(2)-induced DNA and cell damage in the human skin fibroblast cell. These extracts showed a dose-dependent free-radical scavenging capacity and a protective effect on DNA damage and the lipid peroxidation causing the cell damage by ROS. These antioxidant activities and inhibitory effects of the extracts on DNA and cell damage may further explain that C. officinale is useful as a herbal medicine for cancer chemoprevention.

96.Herbal plants as a promising source of natural antifoulants: evidence from barnacle settlement inhibition.:

Biofouling. 2009;25(3):181-90.
 A series comprising hexane, ethyl acetate, ethanol and aqueous extracts from six common Chinese herbs (Carpesium abrotanoides, Melia toosendan, Cnidium monnieri, Vitex negundo, Stemona sp. and Sophora flavescens) was investigated for antifouling (AF) activity against cypris (cyprids) larvae of the barnacle Balanus albicostatus. All extracts tested except the aqueous extract from Stemona sp. significantly inhibited the settlement of cyprids, the most potent being the ethyl acetate extract of S. flavescens (EC(50) value 2.08 microg ml(-1)), from which an AF compound, identified as 2'-methoxykurarinone, was isolated using bioassay-guided procedures. Furthermore, the AF activity of this compound was found to be highly reversible and greater than that of the three other natural products from S. flavescens, namely matrine, oxymatrine and oxysophocarpine. These compounds have been used commercially in China for their pharmaceutical activities, but their AF activities have not previously been evaluated. Analysis of structure-activity relationships suggested that the N-1 nitrogen atom in matrine plays a crucial role in AF activity. Overall, the present findings indicate that herbal plants are a valuable source of novel AF agents.

97.In vitro effect of Chinese herb extracts on caries-related bacteria and glucan.:

J Vet Dent. 2008 Dec;25(4):236-9.
 The purpose of this study was to evaluate the inhibitory effects of herb extracts on caries-related bacteria and glucan of dental plaque in vitro. Bacterial sensitivity tests were done using broth dilution, and the phenol sulphate method was used to assess glucan inhibition. The results showed that tannic acid could inhibit bacterial growth more effectively than other herb extracts. Eugenol showed a 46.87 +/- 12.74 and 36.67 +/- 6.30% inhibitory effect on insoluble and soluble glucan synthesis, respectively. Cnidium, barbaloin, caryophyllin, and piperine had > 40.0% inhibitory effect on soluble glucan synthesis. Both insoluble and soluble glucan synthesis of S. sobrinus were inhibited by eugenol and piperine. Eugenol and piperine were efficacious in inhibiting glucan synthesis making them desirable agents for oral care products.

98.Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.:

BMC Cancer. 2009 Mar 17;9:85.
 Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. METHODS: HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. RESULTS: In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. CONCLUSION: HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

99.Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study.:

Epilepsy Res. 2009 Aug;85(2-3):293-9. Epub 2009 Apr 29.
 The aim of this study was to determine and compare the anticonvulsant and acute adverse (neurotoxic) effects of imperatorin and osthole (two natural coumarin derivatives) with valproate (a classical antiepileptic drug) in the maximal electroshock seizure and chimney tests in mice. The anticonvulsant and acute adverse effects of imperatorin, osthole and valproate were determined at 15, 30, 60 and 120 min after their systemic (i.p.) administration. The evaluation of time-course and dose-response relationships for imperatorin, osthole and valproate in the maximal electroshock seizure test revealed that the compounds produced a clear-cut antielectroshock action in mice and the experimentally derived ED(50) values for imperatorin ranged between 167 and 290 mg/kg, those for osthole ranged from 253 to 639 mg/kg, whereas the ED(50) values for valproate ranged from 189 to 255 mg/kg. The evaluation of acute neurotoxic effects in the chimney test revealed that the TD(50) values for imperatorin ranged between 329 and 443 mg/kg, the TD(50) values for osthole ranged from 531 to 648 mg/kg, while the TD(50) values for valproate ranged from 363 to 512 mg/kg. The protective index (as a ratio of TD(50) and ED(50) values) for imperatorin ranged between 1.13 and 2.60, for osthole ranged from 0.83 to 2.44, and for valproate ranged between 1.72 and 2.00. In conclusion, both natural coumarin derivatives deserve more attention from a preclinical point of view as compounds possessing some potentially favorable activities in terms of suppression of seizures, quite similar to those reported for valproate.

100.Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong Hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell.:

Cancer Epidemiol. 2009 Jul;33(1):41-6. Epub 2009 May 27.
 Owing to their high volatile aroma, the dried rhizomes of Cnidium officinale (C. officinale) and Ligusticum chuanxiong (L. chuanxiong) are used as herbal drugs to treat blood pressure depressant, a deficiency disease of antivitamin, inhibition of small intestine sympathetic nerve and as cosmetics for skin care. However, little has been known about the protective effect of their essential oils against ultraviolet B (UVB)-induced DNA damage. METHODS: In this study, we report antioxidant activity of their essential oils using DPPH and ABTS scavenging assay. In addition, the composition of essential oils was measured by GC/MS. We also investigated whether these essential oils could inhibit UVB-induced DNA damage and apoptosis in the mammalian cell using intracellular DNA migration and expression level of phospho-H2A.X. RESULTS: Twenty constituents in the essential oil were identified and they showed good antioxidant properties, in that IC(50) value in DPPH and ABTS showed 6.79 and 7.33microg/ml and 1.58 and 1.58microg/ml in C. officinale and L. chuanxiong. Their treatment inhibited the migration of damaged DNA induced by UV-B; furthermore, they decreased p21 expression and increased cyclin D1 expression as apoptosis-regulatory genes. CONCLUSIONS: These results suggest that essential oils in C. officinale and L. chuanxiong may exert inhibitory effects on DNA damage and apoptosis induced by UVB through their high free radical scavenging ability.

101.Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice.:

Chem Biol Interact. 2009 Oct 30;181(3):309-15. Epub 2009 Aug 12.
 Osthole is an agent isolated from Cnidium monnieri (L.) Cusson and Angelica pubescens and has been used to treat several diseases, including metabolic syndromes. To investigate the hypoglycemic effects of osthole in diabetic db/db mice and the underlying mechanisms of these effects by in vitro assay, diabetic db/db mice and cell experiments were utilized to understand its possible effects. Osthole significantly activated both PPARalpha and PPARgamma in a dose-dependent manner based on the results of the transition transfection assay. The activation of PPARalpha and PPARgamma by osthole also resulted in an increase in the expression of PPAR target genes such as PPAR itself, adipose fatty acid-binding protein 2, acyl-CoA synthetases, and carnitine palmitoyltransferase-1A. In vitro results suggested that osthole might be a dual PPARalpha/gamma activator, but its chemical structure differed from that of the thiazolidinedione class of antidiabetic drugs. In addition, osthole markedly activated the AMP-activated protein kinase and its downstream acetyl CoA carboxylase molecules by increasing their phosphorylation levels. Finally, obese diabetic db/db mice were treated with osthole by different administered routes, and osthole was found to markedly reduce blood glucose level. Interestingly, osthole did not reduce the blood insulin or lipid levels, two phenomena that did occur in animals treated with insulin sensitizers like PPAR agonists. These results suggest that osthole can alleviate hyperglycemia and could be potentially developed into a novel drug for treatment of diabetes mellitus.

102.Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5.:

J Mol Graph Model. 2009 Oct;28(3):261-9. Epub 2009 Aug 8.
 The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile dysfunction since the ancient Han dynasty (202 BC-AD 220). Phosphodiesterase-5 (PDE-5) is deemed the target protein for inhibition to treat erectile dysfunction. In this study, a reliable multiple linear regression (MLR) model (r value=0.8484) was used to predict the activities of new candidates which were designed from ES, CM, and SC. From docking and pharmacophore analysis, the potent candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were predicted to have high potencies based on MLR analysis and high docking scores. Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding site, inhibitors with molecular weights over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors from TCM and provides a scientific basis for confirming pharmacological actions of TCM.

103.Evaluation of the phototoxic potential of plants used in oriental medicine.:

J Ethnopharmacol. 2010 Jan 8;127(1):11-8. Epub 2009 Oct 7.
 AIM OF THE STUDY: Phototoxicity can be either harmful or beneficial. Yet the phototoxicity of oriental medicinal plants is an understudied area. The purpose of this study is to fill in this gap. MATERIALS AND METHODS: The phototoxic potential of oriental medicinal plants was examined in vitro using photohemolysis and the Candida albicans test. Seventeen medicinal plants [Acorus gramineus (ACG), Panax ginseng C.A. (PAG), Platycodon grandiflorum (PLG), Aractylodes japonica (ATJ), Xanthium strumarium (XAS), Dioscorea batatas (DIB), Anemarrhena asphodeloides (ANA), Polygonatum sibiricum Red (PSR), Cocculus trilobus (COT), Ficus carica (FIC), Chelidonium majus var. asiaticum (CMA), Pulsatilla koreana (PUK), Agrimonia pilosa (AGP), Zanthoxylum schinifolium (ZAS), Angelica gigas (ANG), Ledebouriella seseloides (LES), and Cnidium officinale (CNO)] were selected because they showed strong fluorescence in one of our previous studies of 62 plants. We further evaluated in vivo phototoxicity in mice. 0.75 mL/kg of seed oil for Xanthium strumarium (XAS, ), or 1.25 mL/kg of extracted solutions of Atractylodes japonica (ATJ, ), Chelidonium majus var. asiaticum (CMA, ), Zanthoxylum schinifolium (ZAS, ), and Ledebouriella seseloides (LES, ) were given once, and evaluated for sunburn edema, formation of sunburn cell, decrease of epidermal Langerhans cells and local suppression of contact hypersensitivity by UVA irradiation. RESULTS: Sixteen out of the 17 plants tested except COT showed significant photohemolysis, and 5 of those exhibited phototoxic killing of Candida albicans. The phototoxicity of oriental medicines using those 5 plants was then studied in mice. The 5 plants increased sunburn edema and formation of sunburn cell, and suppressed immune responses locally by decreasing epidermal Langerhans cells and contact hypersensitivity by UVA irradiation. CONCLUSIONS: More than a quarter of oriental medicinal plants can be phototoxic, and strong fluorescence measured by absorption and fluorescence spectra can be an easier way to screen for phototoxicity. On the other hand, the phototoxicity of the plants may also be used therapeutically. Further studies regarding the phototoxicity of active components extracted from both live and dried oriental medicinal plants are necessary.

104.Osthole or imperatorin-mediated facilitation of glutamate release is associated with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve endings.:

Synapse. 2010 May;64(5):390-6.
 Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, have previously been shown to facilitate depolarization-evoked glutamate release from rat hippocampal nerve terminals by increasing voltage-dependent Ca(2+) entry. In this study, we further investigated whether osthole and imperatorin possess an action at the exocytotic machinery itself, downstream of a Ca(2+) influx. Our data showed that ionomycin-induced glutamate release and KCl-evoked FM1-43 release were facilitated by osthole and imperatorin, suggesting that some steps after Ca(2+) entry are regulated by these two compounds. Consistent with this, osthole or imperatorin-mediated facilitation of ionomycin-induced glutamate release was occluded by cytochalasin D that inhibits actin polymerization, implying that the disassembly of cytoskeleton is involved. In addition, the facilitatory action of osthole or imperatorin on ionomycin-induced glutamate release was attenuated by the Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor KN62. Furthermore, Western blotting analysis further showed that osthole or imperatorin significantly increased ionomycin-induced phosphorylation of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results suggest, therefore, that osthole or imperatorin-mediated facilitation of glutamate release involves modulation of downstream events controlling synaptic vesicle recruitment and exocytosis, possibly through an increase of CaMKII activation and synapsin I phosphorylation, thereby increasing synaptic vesicle availability for exocytosis.

105.Osthol regulates hepatic PPARalpha-mediated lipogenic gene expression in alcoholic fatty liver murine.:

Phytomedicine. 2009 Dec 28.
 Our previous studies found that osthol, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), could ameliorate the accumulation of lipids and decrease the lipid levels in serum and hepatic tissue in alcohol-induced fatty liver mice and rats. The objective of this study was to investigate its possible mechanism of the lipid-lowering effect. A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthol 10, 20, 40mg/kg for 4 weeks. The BRL cells (rat hepatocyte line) were cultured and treated with osthol at 25, 50, 100, 200mug/ml for 24h. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) alpha, diacylglycerol acyltransferase (DGAT), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and cholesterol 7alpha-hydroxylase (CYP7A) in mouse hepatic tissue or cultured hepatocytes were determined by reverse transcription polymerase chain reaction (RT-PCR). After treatment with osthol, the PPARalpha mRNA expression in mouse liver and cultured hepatocytes was increased in dose dependent manner, while its related target genes for mRNA expression, e.g., DGAT and HMG-CoA reductase, were decreased, the CYP7A was inversely increased. And osthol-regulated mRNA expressions of DGAT, HMG-CoA reductase and CYP7A in the cultured hepatocytes were abrogated after pretreatment with specific inhibitor of PPARalpha, MK886. It was concluded that osthol might regulate the gene expressions of DGAT, HMG-CoA reductase and CYP7A via increasing the PPARalpha mRNA expression.

106.HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.:

J Med Food. 2010 Feb;13(1):47-53.
 Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

107.Effects of osthole on apoptosis and TGF-beta1 of hypertrophic scar fibroblasts.:

J Asian Nat Prod Res. 2009 Jul;11(7):663-9.
 Osthole, 7-methoxy-8-[3-methylpent-2-enyl]coumarin (1), was extracted from a Chinese herb Cnidium monnieri (L.) Cuss. It showed immunity strengthening, anti-tumor, anti-hepatitis, and anti-osteoporosis activities in previous studies. Our goals are to study the effects of 1 on cell proliferation and TGF-beta of hypertrophic scar fibroblasts. Our results showed that 1 induced apoptosis and inhibited cell proliferation in hypertrophic scar fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that its IC(50) value toward hypertrophic scar fibroblasts was 15.5 +/- 2.2 micromol/l. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by 1 in hypertrophic scar fibroblasts was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical 'Sub-G(1) peak' was also checked through flow cytometry. We used immunohistochemistry to observe the expression of TGF-beta(1). Also, we found that 1 could obviously inhibit the expression of TGF-beta(1) of fibroblasts derived from hypertrophic scar compared with the control group (P < 0.05). These results suggest that 1 inhibits the growth of hypertrophic scar fibroblasts through apoptosis and decreases the expression of TGF-beta(1).

108.Osthole Suppresses Fatty Acid Synthase Expression in HER2-Overexpressing Breast Cancer Cells through Modulating Akt/mTOR Pathway.:

J Agric Food Chem. 2010 Mar 10
 While fatty acid synthase (FASN) has been shown to be expressed in many human solid tumors, FASN has also been identified in preneoplastic lesions. HER2, which has also been identified in preneoplastic breast lesions, has been shown to upregulate FASN expression. Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a traditional Chinese medicine, was found to be effective in suppressing FASN expression in HER2-overexpressing breast cells. Osthole preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Moreover, osthole inhibited the phosphorylation of Akt and mTOR. The use of Akt-overexpression revealed that the modulation of Akt and mTOR was required for osthole-induced FASN suppression. Finally, we showed that osthole could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells. These results suggested that osthole has the potential to advance as chemopreventive or chemotherapeutic agent for cancers that overexpress HER2.

Reference:

• 1.What is Cnidium Monnier Extracts?Pharmacology Actions and application of Cnidium Monnier and Osthol,C15H16O3,Osthola?

This article written and edited via herbalist of MDidea Extracts Professional. They run a range of online descriptions about this herb,including general information related and summarized updating discoveries from findings of professional scientisits this field related.Describe style aimed to form a useful detecting literature space where the intertwined threshold and related questions raise out and visualize themselves.

♣ last edit date:08th,Oct.2010.