Research update of Perilla related.

  seminal trace...Red Perilla leaf Extracts.Perilla Seed Extracts,Rosemarinic Acid 10%20%UV.20283-92-5.Rosemary acid.M.W.C18 H16O8.Red Perilla leaf Stem Extracts.Sclareol,CAS 515-03-7....

   Phytochemical info of Red Perilla leaf Extract:

 Product Name:
 Synonym:
 Definition: Red Perilla leaf Extract are majorly composed of
 Chemical information disclosed as following table:


   Research Update of Galla Chinensis:

   Anthocyanin and flavonoid production from Perilla frutescens: pilot plant scale processing including cross-flow microfiltration and reverse osmosis.:

 J Agric Food Chem. 2006; 54(12):4297-303 (ISSN: 0021-8561).Meng L; Lozano Y; Bombarda I; Gaydou E; Li B.Centre de Coop??ration Internationale en Recherche Agronomique pour le D??veloppement, UMR G??nie des Proc??d??s et Elaboration des Bioproduits, TA 40/16, 73 Avenue Agropolis, 34398 Montpellier Cedex 5, France.

 Extraction and concentration at a pilot plant scale of anthocyanins and flavonoids from Perilla frutescens var. frutescens harvested in the Guangzhou area of China were investigated. The study of extraction efficiency using mineral acids and organic acids showed that 0.01 mol/L nitric acid was the most suitable to extract flavonoids from this slightly red leaf cultivar. The red extract contained 12 mg/L (as cyanidin equivalent) anthocyanins and other flavones. The multistep process included cross-flow microfiltration (CFM) with a ceramic type membrane, reverse osmosis (RO), and rotating evaporation (RE). The filtration fluxes were high and constant for CFM (150 L/h/m2 at 0.6 b) and for RO (22 L/h/m2 at 40 b). The red extract was concentrated 9.4 times by RO and then 5.4 times by RE. It contained 422 mg/L anthocyanins, representing 77% of the total extracted anthocyanin. The proportion of flavonoids was found unchanged during processing. The concentrated extract showed a pH of 2.7, and its free acidity was found to be 46% of the acidity added for extraction, because of the buffering capacity of the extract. At the concentration level reached, a crystallized deposit occurred and was identified as tartrate.

   Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects.:Biosci Biotechnol Biochem. 2004; 68(1):85-90 (ISSN: 0916-8451).

 Nine triterpene acids, viz., six of the ursane type, ursolic acid (1), corosolic acid (2), 3-epicorosolic acid (3), pomolic acid (4), tormentic acid (5) and hyptadienic acid (6), and three of the oleanane type, oleanolic acid (7), augustic acid (8) and 3-epimaslinic acid (9), among which 1 constituted the most predominant triterpene acid, were isolated and identified from ethanol extracts of the leaves of red perilla [Perilla frutescens (L.) Britton var. acuta Kudo] and green perilla [P. frutescens (L.) Britton var. acuta Kudo forma viridis Makino]. These eight compounds, 1, 2, 4-9, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice. All the compounds tested showed a marked anti-inflammatory effect, with a 50% inhibitory dose (ID50) of 0.09-0.3 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA showed five compounds, 1-3, 5 and 9, with a potent inhibitory effect on EBV-EA induction (91-93% inhibition at 1x10(3) mol ratio/TPA). Furthermore, compound 5 exhibited strong antitumor-promoting activity in an in vivo two-stage carcinogenesis test of mouse tumor by using 7,12-dimethylbenz(a)anthracene (DMBA) as an initiator and TPA as a promoter.

   Inotropic and lusitropic effects of Perilla frutescens (L.) Britton extract on the rabbit myocardium.:Medicina (Kaunas). 2006; 42(5):406-12 (ISSN: 1648-9144).Korotkich I; Senikiene Z; Simoniene G; Lazauskas R; Laukeviciene A; Kevelaitis E.Department of Physiology, Kaunas University of Medicine, Kaunas, Lithuania. igor@kmu.lt.

 BACKGROUND: Common perilla (Perilla frutescens (L.) Britton) is a plant cultivated in many countries around the world. Although its immunomodulating and antioxidative properties are well known, there is a lack of data about the cardiotropic activity of the plant. The objective of this study was to determine the influence of Perilla frutescens extract on the myocardial contractility in vitro and as a food supplement in vivo. MATERIAL AND METHODS: Rabbits of the experimental group were fed with a supplement of 100 mg/kg of Perilla frutescens extract for 14 days. Rabbits of control group were fed with ordinary food. The maximal mechanical activity of isolated myocardial preparations, obtained from the rabbits of both groups, was tested during the perfusion with Ringer's solution containing 5 microM of adrenaline and 4.5 mM of CaCl2. For the assessment of the direct influence of Perilla frutescens extract on the myocardial contractility in vitro isolated heart preparations were perfused with 0.01, 0.1, and 1.0 mg/ml of Perilla frutescens extract. RESULTS: The maximum force of isometric contraction, maximum velocity of force development, and maximum velocity of relaxation were higher among the atrial and ventricular preparations from the experimental group, as compared with the control group. Perfusion of the myocardial preparations with different concentrations of Perilla frutescens extract revealed slight dose-dependent increase in the parameters of contraction and relaxation. CONCLUSIONS: The consumption of Perilla frutescens extract as a food supplement leads to an increase in the contractility of the rabbit myocardium. Perilla frutescens extract in vitro had a dose-dependent positive inotropic and lusitropic effect on the rabbit myocardium.

   Common perilla (Perilla frutescens (L.) Britton.) as a perspective immunomodulator.:Medicina (Kaunas). 2004; 40(3):220-4 (ISSN: 1648-9144).Ragazinskiene O; Gailys V; Jankauskiene K; Simoniene G; Jurkstiene V.Kaunas Botanical Garden, Vytautas Magnus University, Z. E. Zilibero 6, 3018 Kaunas, Lithuania. o.ragazinskiene@bs.vdu.lt

 Common perilla (Perilla frutescens (L.) Britton) is a new perspective annual medicinal dead-nettle family (Lamiaceae Lindl.) plant in Lithuania. Its medicinal raw material and preparations produced of it are characterised by the variety of pharmacological effects: desensitizing, antimicrobial, anti tumorous, and antioxidative. This species was introduced from the East Asia and cultivated in many European, Asian, and North American countries. The common perilla has been cultivated in Lithuania as a decorative plant in parks and squares since 1990. This plant has been introduced in the collection and exposition of medicinal plants in Kaunas Botanical Garden of Vytautas Magnus University since 1998 with the purpose to analyze biological and pharmacological properties of plants and to assess the quality and quantity of the raw herb. It would be reasonable to carry out experimental research on biological qualities and raw material of the common perilla in Lithuania in accordance with the contemporary technologies and requirements of the European Union standards.

   Policosanol content and composition in perilla seeds.:J Agric Food Chem. 2006; 54(15):5359-62 (ISSN: 0021-8561).Adhikari P; Hwang KT; Park JN; Kim CK.Department of Food Science and Human Nutrition, and Center for Healthcare Technology Development, Chonbuk National University, Jeonju 561-756, Korea.

 Policosanols, long-chain alcohols, have many beneficial physiological activities. Contents and compositions in perilla seeds (Perilla frutescens) produced in Korea and China were determined. Waxy materials were extracted from perilla seeds using hot hexane. Yield of the waxy materials from perilla seeds was 72.1 mg/100 g of dry weight. Contents and compositions of the waxy materials and policosanols were identified and quantified by TLC, HPLC, and GC. Major components of the waxy materials from Korean and Chinese perilla seeds were policosanols (25.5 and 34.8%, respectively), hydrocarbons (18.8 and 10.5%), wax esters, steryl esters and aldehydes (53.0 and 49.8%), acids (1.7 and 2.1%), and triacylglycerols (1.0 and 2.9%), determined by HPLC. For comparison, waxy materials of sesame seeds were also analyzed. Yield of the waxy materials from sesame seeds were 8.6 mg/100 g. Less than 5% policosanols were detected in the waxy materials extracted from sesame seeds produced in Korea and China. Wax esters or steryl esters accounted for 93-95% of the sesame waxy materials. Policosanols in the perilla seeds were composed of 67-68% octacosanol, 16-17% hexacosanol, 6-9% triacontanol, and others.


   Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model.:Clin Exp Allergy. 2004; 34(6):971-7 (ISSN: 0954-7894)

 BACKGROUND: Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. OBJECTIVE: The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. METHODS: C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5 mg/mouse/day). RESULTS: Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. CONCLUSION: These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody.

   Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans.:Exp Biol Med (Maywood). 2004; 229(3):247-54 (ISSN: 1535-3702).

 Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, suppresses allergic immunoglobulin responses and inflammation caused by polymorphonuclear leukocytes (PMNL) in mice. However, few placebo-controlled clinical trials have examined the efficacy and safety of polyphenolic phytochemicals for treatment of allergic inflammatory diseases in humans. The present study determined whether oral supplementation with rosmarinic acid is an effective intervention for patients with seasonal allergic rhinoconjunctivitis (SAR). In this 21-day, randomized, double-blind, age-matched, placebo-controlled parallel group study, patients with mild SAR were treated daily with extract of Perilla frutescens enriched for rosmarinic acid (200 mg [n=10] or 50 mg [n=9]) or placebo (n=10). Patients recorded symptoms daily in a diary. Profiles of infiltrating cells and concentrations of eotaxin, IL-1beta, IL-8, and histamine were measured in nasal lavage fluid. Serum IgE concentrations and routine blood tests were also examined. As compared with placebo supplementation, supplementation with extract of Perilla frutescens enriched for rosmarinic acid resulted in a significant increase in responder rates for itchy nose, watery eyes, itchy eyes, and total symptoms (P<0.05). Active treatment significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid (P<0.05 vs. placebo). Patients reported no adverse events, and no significant abnormalities were detected in routine blood tests. In conclusion, extract of Perilla frutescens enriched for rosmarinic acid can be an effective intervention for mild SAR at least partly through inhibition of PMNL infiltration into the nostrils. Use of this alternative treatment for SAR might reduce treatment costs for allergic diseases.

   Anti-allergic effect of Perilla frutescens and its active constituents.:Phytother Res. 2003; 17(3):240-3 (ISSN: 0951-418X).

 The leaves of Perilla frutescens Britton (Labiatae) are one of the most popular garnishes in China, used as an antidote for fi sh and crab meat allergy or as a food colorant. The present study was conducted to evaluate its anti-allergic effect and to identify its active constituents using mice ear-passive cutaneous anaphylaxis (PCA)-reaction. 48 h after the cutaneous injection of anti-ovalbumin serum into the ears of mice, ovalbumin and evansblue dye were intravenously injected. Perilla was extracted with boiling water, and intraperitoneally injected 15 min before ovalbumin-treatment. Thirty min after ovalbumin-treatment, the ears were removed and the colorant in the ear was colorimetrically quantitated. Perilla extract significantly suppressed the PCA-reaction, which was brought about by rosmarinic acid with a partial contribution from some macromolecular compounds. The anti-allergic titer of rosmarinic acid was more effective than tranilast, which is a modern anti-allergic drug. Perilla and rosmarinic acid are potentially promising agents for the treatment of allergic diseases.

   Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects.:Biosci Biotechnol Biochem. 2004; 68(1):85-90 (ISSN: 0916-8451)

 Nine triterpene acids, viz., six of the ursane type, ursolic acid (1), corosolic acid (2), 3-epicorosolic acid (3), pomolic acid (4), tormentic acid (5) and hyptadienic acid (6), and three of the oleanane type, oleanolic acid (7), augustic acid (8) and 3-epimaslinic acid (9), among which 1 constituted the most predominant triterpene acid, were isolated and identified from ethanol extracts of the leaves of red perilla [Perilla frutescens (L.) Britton var. acuta Kudo] and green perilla [P. frutescens (L.) Britton var. acuta Kudo forma viridis Makino]. These eight compounds, 1, 2, 4-9, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice. All the compounds tested showed a marked anti-inflammatory effect, with a 50% inhibitory dose (ID50) of 0.09-0.3 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA showed five compounds, 1-3, 5 and 9, with a potent inhibitory effect on EBV-EA induction (91-93% inhibition at 1x10(3) mol ratio/TPA). Furthermore, compound 5 exhibited strong antitumor-promoting activity in an in vivo two-stage carcinogenesis test of mouse tumor by using 7,12-dimethylbenz(a)anthracene (DMBA) as an initiator and TPA as a promoter.

   Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model.:Carcinogenesis. 2004; 25(4):549-57 (ISSN: 0143-3334).

 Perilla frutescens extract showed marked reduction on tumorigenesis in a murine, two-stage skin carcinogenesis model. In this model, cancer is initiated by application of 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by application of 12-tetradecanoylphorbol 13-acetate (TPA). Following tumor initiation with DMBA, topical application of a perilla-derived fraction (PF) at doses of 2 mg/mouse/application resulted in significant inhibition of tumorigenesis. The efficacy of each fraction was correlated with rosmarinic acid (RA) and luteolin concentration. Topical application of perilla extract (PE) that contained 68% RA or an equivalent amount of commercially available RA showed nearly identical antiinflammatory activity 5 h after TPA treatment. Application of luteolin had less anti-inflammatory activity. Marked neutrophil infiltration was observed in TPA-challenged skin by histological examination using hematoxylin-eosin. This change was greatly reduced by pre-treatment with PE or RA. Myeloperoxidase activity, a marker of neutrophil recruitment, was also increased in TPA-challenged skin and was significantly decreased in the PE and RA treated groups. Intercellular adhesion molecule 1 and vascular cell adhesion molecule-1 mRNA expression levels were reduced by pre-treatment with PE or RA. TPA-induced increases in synthesis of the chemokines KC and macrophage inflammatory protein-2 were significantly decreased by pre-treatment with PE or RA. Prostaglandin E2 and leukotriene B4 levels were slightly increased 5 h after TPA treatment. These levels were only numerically decreased in the PE and RA treated groups. However, induction of cyclooxygenase-2 mRNA expression was obviously reduced by pre-treatment with PE or RA. Reactive oxygen radical production, detected as thiobarbituric acid reactive substance and lipid peroxide, by double treatment of TPA was reduced by pre-treatment with PE or RA. Production of 8-hydroxy-2'deoxyguanosine, which was detected immunohistochemically, was also induced by double treatment with TPA. This adduct was barely visible in PE or RA treated mice. Thus, we conclude that part of the anticarcinogenic effects of P.frutescens extract is due to RA via two independent mechanisms: inhibition of the inflammatory response and scavenging of reactive oxygen radicals.


   Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans.:Eur J Nutr. 2005; 44(1):1-9 (ISSN: 1436-6207).

 BACKGROUND: Rosmarinic acid (RA) is a natural polyphenolic substance contained in many Lamiaceae herbs such as Perilla frutescens. Previous studies have shown RA has antioxidative and anti-inflammatory activity. However, little is known on the absorption, metabolism, degradation and excretion of RA. AIM OF THE STUDY: The aim of this study in healthy humans was to determine the absorption, metabolism, and urinary excretion of RA after a single intake of perilla extract (PE). METHOD: Six healthy men (mean age 37.2 +/- 6.2 y and mean body mass index 22.0 +/- 1.9 kg/m(2)) were enrolled in the study that was a crossover design involving single intakes of PE containing 200 mg RA and placebo with a 10 day interval between treatments. Blood samples were collected before intake and at designated time intervals, while urine samples were collected over the periods 0-6 h, 6-24 h and 24-48 h after intake. RA and its related metabolites in plasma and urine were measured by LC-MS. RESULTS: RA, methylated RA (methyl-RA), caffeic acid (CAA), ferulic acid (FA) and a trace of m-coumaric acid (COA) were detected in the urine after intake of PE. In plasma, RA, methyl-RA and FA were detected, with maximum levels obtained 0.5, 2 and 0.5 h after intake of PE, respectively. The majority of these components in both plasma and urine were present as conjugated forms (glucuronide and/or sulfated). The proportion of RA and its related metabolites excreted in the urine was 6.3 +/- 2.2% of the total dose, with approximately 75% of these components being excreted within 6 h after intake of PE. CONCLUSIONS: RA contained in PE was absorbed, conjugated and methylated following intake, with a small proportion of RA being degraded into various components, such as conjugated forms of CAA, FA and COA. These metabolites were then rapidly excreted in the urine.

   Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens.:Biol Pharm Bull. 2002; 25(9):1197-202 (ISSN: 0918-6158).

 Oral administration of the perilla leaf extract (PLE) to mice inhibits inflammation, allergic response, and tumor necrosis factor-alpha production. We also found that PLE suppressed the tumor necrosis factor-alpha (TNF-alpha) production in vitro. Using the inhibitory activity of TNF-alpha production in vitro as the index for isolation, we searched the active constituents from PLE and isolated luteolin, rosmarinic acid and caffeic acid as active components. Among the isolated compounds, only luteolin showed in vivo activity: inhibition of serum tumor necrosis factor-alpha production, inhibition of arachidonic acid-induced ear edema, inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ear edema and inhibition of oxazolone-induced allergic edema. These results suggest that luteolin is a genuinely active constituent which is accountable for the oral effects of perilla.

   High-performance liquid chromatographic analysis of bioactive triterpenes in Perilla frutescens.:J Pharm Biomed Anal. 2003; 32(6):1175-9 (ISSN: 0731-7085).Chen JH; Xia ZH; Tan RX.State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing 210093, China.

 Perilla frutescens (L.) Britt. (Lamiaceae), a famous traditional Chinese medicine, has been used for the treatment of various diseases. To evaluate the quality of P. frutescens, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed for the assessment of three bioactive triterpene acids: tormentic acid (TA), oleanolic acid (OA) and ursolic acid (UA). The HPLC system used an Spherisob octadecylsilyl silica (ODS) column with acetonitrile and aqueous H(3)PO(4) as the mobile phase and detection at 206 nm. The method was precise with relative standard deviations for these three constituents that ranged between 0.6-1.5% (intraday) and 0.7-2.6% (interday). The content of these three phytochemicals in the leaves of P. frutescens growing at eight different locations of China was determined to establish the effectiveness of the method.

   Anthocyanin and flavonoid production from Perilla frutescens: pilot plant scale processing including cross-flow microfiltration and reverse osmosis.:

 J Agric Food Chem. 2006; 54(12):4297-303 (ISSN: 0021-8561).Meng L; Lozano Y; Bombarda I; Gaydou E; Li B.Centre de Coop??ration Internationale en Recherche Agronomique pour le D??veloppement, UMR G??nie des Proc??d??s et Elaboration des Bioproduits, TA 40/16, 73 Avenue Agropolis, 34398 Montpellier Cedex 5, France.

 Extraction and concentration at a pilot plant scale of anthocyanins and flavonoids from Perilla frutescens var. frutescens harvested in the Guangzhou area of China were investigated. The study of extraction efficiency using mineral acids and organic acids showed that 0.01 mol/L nitric acid was the most suitable to extract flavonoids from this slightly red leaf cultivar. The red extract contained 12 mg/L (as cyanidin equivalent) anthocyanins and other flavones. The multistep process included cross-flow microfiltration (CFM) with a ceramic type membrane, reverse osmosis (RO), and rotating evaporation (RE). The filtration fluxes were high and constant for CFM (150 L/h/m2 at 0.6 b) and for RO (22 L/h/m2 at 40 b). The red extract was concentrated 9.4 times by RO and then 5.4 times by RE. It contained 422 mg/L anthocyanins, representing 77% of the total extracted anthocyanin. The proportion of flavonoids was found unchanged during processing. The concentrated extract showed a pH of 2.7, and its free acidity was found to be 46% of the acidity added for extraction, because of the buffering capacity of the extract. At the concentration level reached, a crystallized deposit occurred and was identified as tartrate.

   Comparison of peptides in the phloem sap of flowering and non-flowering Perilla and lupine plants using microbore HPLC followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.:

 Planta. 2002; 216(1):140-7 (ISSN: 0032-0935).Hoffmann-Benning S; Gage DA; McIntosh L; Kende H; Zeevaart JA.Michigan State University, MSU-DOE Plant Research Laboratory and Department of Biochemistry and Molecular Biology, East Lansing, MI 48824, USA.

 Physiological evidence indicates that flower formation is hormonally controlled. The floral stimulus, or florigen, is formed in the leaves as a response to an inductive photoperiod and translocated through the phloem to the apical meristem. However, because of difficulties in obtaining and analyzing phloem sap and the lack of a bioassay, the chemical nature of this stimulus is one of the major unsolved problems in plant biology. A combination of microbore high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to compare the contents of the phloem sap from flowering and non-flowering plants. Instead of using one- or two-dimensional gel electrophoresis, microbore HPLC separations allowed us to detect proteins/peptides that were very small and present at very low levels. We detected more than 100 components in the phloem sap of Perilla ocymoides L. and Lupinus albusL. Sequences for 16 peptides in a mass range from 1 to 9 kDa were obtained. Two of these could be identified, 11 showed similarity to known or deduced protein sequences, and three showed no similarity to any known protein or translated gene sequence. Four of these peptides were specific to, modified, or increased in plants that were flowering, indicating their possible role in flower induction. The sequences of these peptides showed similarities to two purine permeases, a protein with similarity to protein kinases, and a protein with no similarities to any known protein.


   Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test.:Biol Pharm Bull. 2003; 26(4):474-80 (ISSN: 0918-6158).

 We studied the effects of apigenin and 2,4,5-trimethoxycinnamic acid (TMCA) on the behavioral despair test (forced swimming test), and the central noradrenergic, dopaminergic and serotonergic activities in mice. Apigenin at intraperitoneal doses of 12.5 and 25 mg/kg significantly decreased the duration of immobility in the forced swimming test in mice. At 100 mg/kg, the duration of immobility was returned to the control level in the test. On the other hand, TMCA treatment (25-200 mg/kg, i.p.) failed to significantly alter the duration of immobility. Based on the behavioral data, we examined changes in the monoamine turnover in mice having been subjected to forced swimming for 40 min. The monoamine turnover was measured in seven brain regions. Forced swimming exposure induced a significant decrease in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) in the striatum and amygdala and in 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytriptamine (5-HT) in the hypothalamus, and a significant increase in DOPAC/DA in the thalamus and hypothalamus and in 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)/norepinephrine (NE) in the amygdala, frontal cortex, hypothalamus, and midbrain. Apigenin (25 mg/kg) treatment produced attenuation of forced swim test-induced decrease of DA turnover in the amygdala and increase of DA turnover in the hypothalamus. Furthermore, intraperitoneal administration of haloperidol (0.2 mg/kg), a dopamine D(2) antagonist, blocked the apigenin (25 mg/kg)-induced decrease in immobility in the forced swimming test. These behavioral and biochemical results indicate the antidepressant properties of apigenin, which may be mediated by the dopaminergic mechanisms in the mouse brain.

   Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice.:Biol Pharm Bull. 2001; 24(10):1206-9 (ISSN: 0918-6158)

 Perilla frutescens Britton (perilla, Labiatae) is a medicinal herb prescribed in Saiboku-to, which is a Kampo formula effective for allergic diseases such as bronchial asthma. The present study was conducted to evaluate the anti-allergic effect of orally administered perilla decoction and to identify the active constituents using mice ear-passive cutaneous anaphylaxis (PCA)-reaction, which is one of the animal models for type I allergy. Perilla decoction significantly suppressed PCA-reaction, and the inhibition % at the dose of 500 mg/kg was 43%. The perilla decoction contains 5.3% of luteolin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 1.6% of apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 0.49% of scutellarin, and 2.5% of rosmarinic acid (weight of compound/dried weight of perilla decoction %), respectively. When these constituents were orally administered to mice at the dose equivalent to 500 mg/kg of perilla decoction, rosmarinic acid and apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide] significantly suppressed PCA-reaction, and their inhibition % was 41% (p<0.01) and 32% (p<0.05), respectively. Since the inhibition % or perilla decoction and rosmarinic acid were nearly equal, the anti-allergic effect of perilla decoction depends primarily on rosmarinic acid. The standard Saiboku-to decoction contained 0.013% of rosmarinic acid, which was too low to exhibit anti-allergic activity in a daily dose of Saiboku-to in adults, suggesting that perilla would be prescribed in Saiboku-to to exhibit other pharmacological effects than its anti-allergic activity, such as a sedative.

   Inhibitory effect of Perilla frutescens and its phenolic constituents on cultured murine mesangial cell proliferation.:Planta Med. 1998; 64(6):541-5 (ISSN: 0032-0943).

 The inhibitory effects of Perilla frutescens and its phenolic constituents on cytokine-induced proliferation of murine cultured mesangial cells were investigated. DNA synthesis of mesangial cells stimulated by platelet derived growth factor (PDGF, 10 ng/ml) or tumor necrosis factor (TNF)-alpha (100 U/ml) was inhibited by the extract of P. frutescens (IC50 values, 3.3 and 1.4 micrograms/ml, respectively). The strength of the anti-proliferative activity was nearly equal in various chemotypes of P. frutescens. Caffeic acid, methyl caffeate, rosmarinic acid, and luteolin 7-O-glucuronide-6"-methyl ester were isolated as active constituents from the extract of the typical strain of P. frutescens, and their IC50 values for PDGF-induced mesangial cell proliferation were estimated as 26 microM, 2.6 microM, 1.8 microM, and 4.1 microM, respectively. We also compared the activities of related flavonoids previously isolated from P. frutescens, and luteolin had the highest anti-proliferative activity.

   Inhibition of antigen-specific T helper type 2 responses by Perilla frutescens extract.:Arerugi. 1999; 48(4):443-50 (ISSN: 0021-4884).

 Perilla frutescens leaf extract (PFE) is known as a natural medicine with anti-allergic activities, although its mechanism of action remains unclear. In this study, we examined the effect of PFE on antigen-specific antibody and on cytokine production. Mice were immunized three times (weekly) with sugi basic protein (SBP), a major allergen of cedar pollen, in alum adjuvant. PFE was injected intraperitoneally into mice on day 2 before and on the day of each immunization with SBP in alum adjuvant. Serum anti-SBP IgE and IgG 1 antibody levels were significantly suppressed in mice injected with PFE. Furthermore, the production of interleukin (IL)-4, IL-5 and IL-10 by SBP-stimulated splenocyses also decreased in PFE-injected mice in a dose-dependent manner. However, PFE had no effect on either the serum anti-SBP IgG 2 a antibody levels or on interferon (INF)-gamma production by splenocytes. When splenocytes were stimulated with concanavalin A, there was no difference in cytokine production between mice injected with PFE and control mice injected with vehicle. SBP-specific T cell line established in the presence of PFE from the lymph node cells of mice immunized with SBP showed reduced IL-4, IL-5 and IL-10 production compared with that established in the absence of PFE. In contrast, comparable levels of IFN-gamma production were observed between these two T cell lines. These data suggest that PFE down-regulates Th 2-type cytokine production and prevents the Th 1/Th 2 balance from polarizing toward Th 2-type immune responses.

   Identification of rosmarinic acid as a novel antidepressive substance in the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba).:

 The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are found in some traditional oriental herbal medicines that are primarily used to treat affective disorders such as depression and anxiety. The aim of the present study was to identify the bioactive component in Perillae Herba that possesses antidepressive activity. The effects of a water extract of Perillae Herba and six fractions therefrom were evaluated in mice by use of the forced-swimming test. An oral administration of a water extract of Perillae Herba significantly reduced the duration of immobility. Moreover, 50% methanol extract of the water extract of Perillae Herba and its 30% methanol extract also reduced the duration of immobility. Three-dimensional high-performance liquid chromatography and FAB-MS and NMR spectral analysis clearly showed that the extracts with anti-immobility effects contained abundant rosmarinic acid. The oral and intraperitoneal administration of rosmarinic acid significantly reduced the duration of immobility. In contrast, a water extract from another species of Perillae Herba, which contains only low levels of rosmarinic acid, had no anti-immobility effect. These results suggest that rosmarinic acid may be the main component involved in the antidepressive effect of Perillae Herba in the forced-swimming test. Thus it may be a novel antidepressive substance.


   Pharmacological effects of zisu and baisu.:Zhongguo Zhong Yao Za Zhi. 1997; 22(1):48-51, 63 (ISSN: 1001-5302).Wang J; Tao S; Xing Y; Zhu Z.Ningxia Institute for Drug Control, Yinchuan.

 The extract and volatile oil of zisu (Perilla frutescens) has shown significant antipyretic effect in rabbits and antiemetic effect in pigeons. The fatty oil extracted from its seeds has significant antitussive effect in mice and anti-asthmatic effect in guinea pigs. The extract, volatile oil and fatty oil of Baisu, which is of the same genus as Zisu have the same effects as those of Zisu. The acute toxicities of the extract and fatty oil of Zisu and Baisu, whether by peroral or by intraperitoneal, are similar to each other. These results indicate that Baisu has the same pharmacological effects as Zisu, and thus can be used as a substitute for Zisu.

   Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice.:Eur J Pharmacol. 2002; 449(3):261-7 (ISSN: 0014-2999)

 We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase.


  Scientific References:

  1.What is Rosmarinic Acid?Super Function of RosA,Rosmarinic Acid?
  2.Research update of Perilla related.