Goldenseal Root,Echinacea's partner, broad-spectrum herbs and its uses.
Contents
Research Update:Goldenseal,Hydrastis canadensis.:
Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line.:Cancer Chemother Pharmacol. 2007 Jul 28;Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J.Center of Neurosciences and Cellular Biology, Department of Zoology, University of Coimbra, P3004-597, Coimbra, Portugal.
PURPOSE: Natural products represent a rich reservoir of potential small molecule inhibitors exhibiting antiproliferative and tumoricidal properties. An example is the isoquinoline alkaloid berberine, which is found in plants such as goldenseal (Hydrastis canadensis). Studies have shown that berberine is able to trigger apoptosis in different malignant cell lines, and can also lead to cell cycle arrest at sub-apoptotic doses. A particularly interesting feature of berberine is the fact that it is a fluorescent molecule, and its uptake and distribution in cells can be studied by flow cytometry and epifluorescence microscopy. To test the relationships between berberine uptake, distribution and cellular effect in melanoma cells, K1735-M2 mouse and WM793 human melanoma cells were treated with different concentrations of berberine, and alterations in cell cycle progression, DNA synthesis, cell proliferation, and cell death measured. METHODS: Cell proliferation was measured by sulforhodamine B assays, cell death by flow cytometry, berberine uptake and distribution by laser scanning confocal microscopy and flow cytometry, cell cycle progression by flow cytometry, and DNA synthesis, M-phase, and mitochondrial effects by immunolabeling and epifluorescence microscopy methods. RESULTS: In these melanoma cell lines, berberine at low doses (12.5-50 muM) is concentrated in mitochondria and promotes G1 arrest. In contrast, higher doses (over 50 muM) result in cytoplasmic and nuclear berberine accumulation, and G2 arrest. DNA synthesis is not markedly affected by low doses of berberine, but 100 muM is strongly inhibitory. Even at 100 muM, berberine inhibits cell growth with relatively little induction of apoptosis. CONCLUSION: Berberine displays multiphasic effects in these malignant cell lines, which are correlated with the concentration and intracellular distribution of this alkaloid. These results help explain some of the conflicting information in the literature regarding the effects of berberine, and suggest that its use in clinical development may be more as a cytostatic agent than a cytotoxic compound.
Effects of herbal products and their constituents on human cytochrome P450(2E1) activity.:Food Chem Toxicol. 2007 Jun 15;Raner GM, Cornelious S, Moulick K, Wang Y, Mortenson A, Cech NB.The University of North Carolina at Greensboro, Department of Chemistry and Biochemistry, 414 Science Building, Greensboro, NC 27402, United States.
Ethanolic extracts from fresh Echinacea purpurea and Spilanthes acmella and dried Hydrastis canadensis were examined with regard to their ability to inhibit cytochrome P450(2E1) mediated oxidation of p-nitrophenol in vitro. In addition, individual constituents of these extracts, including alkylamides from E. purpurea and S. acmella, caffeic acid derivatives from E. purpurea, and several of the major alkaloids from H. canadensis, were tested for inhibition using the same assay. H. canadensis (goldenseal) was a strong inhibitor of the P450(2E1), and the inhibition appeared to be related to the presence of the alkaloids berberine, hydrastine and canadine in the extract. These compounds inhibited 2E1 with K(I) values ranging from 2.8muM for hydrastine to 18muM for berberine. The alkylamides present in E. purpurea and S. acmella also showed significant inhibition at concentrations as low as 25muM, whereas the caffeic acid derivatives had no effect. Commercial green tea preparations, along with four of the individual tea catechins, were also examined and were found to have no effect on the activity of P450(2E1).
Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 3: effect on human lens and retinal pigment epithelial cells.:Photochem Photobiol. 2007 Jul-Aug;83(4):938-43.Chignell CF, Sik RH, Watson MA, Wielgus AR.Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, NC, USA. chignell@niehs.nih.gov
The dried root or rhizome of Goldenseal (Hydrastis canadensis L.) contains several alkaloids including berberine, hydrastine, palmatine and lesser amounts of canadine and hydrastinine. Preparations derived from Goldenseal have been used to treat skin and eye ailments. Berberine, the major alkaloid in Goldenseal root powder, has been used in eye drops to treat trachoma, a disease characterized by keratoconjunctivitis. Berberine and palmatine are also present in extracts from Berberis amurensis Ruprecht (Berberidaceae) which are used to treat ocular disorders. We have previously shown that Goldenseal alkaloids are phototoxic to keratinocytes (Chem Res Toxicol. 14, 1529, 2001; ibid 19, 739, 2006) and now report their effect on human lens and retinal pigment epithelial cells. Human lens epithelial cells (HLE-B3) were severely damaged when incubated with berberine (25 microM) and exposed to UVA (5 J cm(-2)). Under the same conditions, palmatine was less phototoxic and hydrastine, canadine and hydrastinine were inactive. Moderate protection against berberine phototoxicity was afforded by the antioxidants ascorbate (2 mM) and N-acetylcysteine (5 mM). When exposed to UVA (5 J cm(-2)) both berberine (10 microM) and palmatine (10 microM) caused mild DNA damage as determined by the alkaline comet assay which measures single strand breaks. Berberine and palmatine are the only Goldenseal alkaloids with appreciable absorption above 400 nm. Because light at wavelengths below 400 nm is cut off by the anterior portion of the adult human eye only berberine and palmatine were tested for phototoxicity to human retinal pigment epithelial (hRPE) cells. Although berberine did damage hRPE cells when irradiated with visible light (lambda > 400 nm) approximately 10 times higher concentrations were required to produce the same amount of damage as seen in lens cells. Palmatine was not phototoxic to hRPE cells. Neither berberine nor palmatine photodamaged DNA in hRPE. Infusions of Goldenseal are estimated to contain approximately 1 mM berberine, while in tinctures the alkaloid concentration may be more than 10 times higher. Our findings show that eyewashes and lotions derived from Goldenseal or containing berberine must be used with caution when the eyes are exposed to bright sunlight but that oral preparations are not likely to cause ocular phototoxicity.
Ethnoveterinary medicines used to treat endoparasites and stomach problems in pigs and pets in British Columbia, Canada.:Vet Parasitol. 2007 Sep 30;148(3-4):325-40. Epub 2007 Jul 12.Lans C, Turner N, Khan T, Brauer G.BCICS, University of Victoria, British Columbia V8W 2Y2, Canada. cher2lans@netscape.net
This paper documents the medicinal plants used to treat endoparasites and stomach problems in dogs, cats and pigs in British Columbia, Canada. Ethnoveterinary data was collected over a 6-month period in 2003. The majority of the information on pets came from 2 naturopaths, 10 herbalists, 5 dog trainers, breeders and pet shop owners, 9 holistic veterinarians and 6 of 27 organic farmers. Two pig farmers joined the study in the final stages. The following plants were used as anthelmintics: Artemisia cina O. Berg and C.F. Schmidt, Artemisia vulgaris L., Artemisia annua, Calendula officinalis L., Echinacea purpurea (L.) Moench (all Asteraceae), Mentha piperita L. and Salvia officinalis L. (Lamiaceae) (Allium sativum L. (Alliaceae), Cucurbita pepo L. (Cucurbitaceae), Eugenia caryophyllata Thunb (Myrtaceae), Gentiana lutea L. (Gentianaceae), Hydrastis canadensis L. (Ranunculaceae), Juglans nigra L. (Juglandaceae), Olea europaea L. (Oleaceae) and Ruta graveolens L. (Rutaceae)). Stomach problems were treated with: Achillea millefolium L. (Asteraceae), Aloe vera (L.) Burm. f. (Asphodelaceae), Elytrigia repens (L.) Desv. ex Nevski (Poaceae), Frangula purshiana (DC.) Cooper (Rhamnaceae), Juniperus communis L. (Cupressaceae), Melissa officinalis L. and M. piperita L. (Lamiaceae), Petroselinum crispum L. (Apiaceae), Plantago major L. and Plantago ovata Forssk. (Plantaginaceae) Rumex crispus L. and Rumex obtusifolius L. (Polygonaceae), Ulmus fulva Michx. (Ulmaceae) and Zingiber officinalis Roscoe (Zingiberaceae). There is insufficient information available to assess the anthelmintic efficacies of C. officinalis, Salvia officinalis, Eugenia caryophyllata and O. europaea; the other plants have mid- to high-level validity for their ethnoveterinary uses.
An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents.:Planta Med. 2007 Jul;73(8):731-41. Epub 2007 Jul 5.Etheridge AS, Black SR, Patel PR, So J, Mathews JM.Health Sciences Unit, Science and Engineering, RTI International, Research Triangle Park, NC 27709-2194, USA.
Drug-herb interactions can result from the modulation of the activities of cytochrome P450 (P450) and/or drug transporters. The effect of extracts and individual constituents of goldenseal, Ginkgo biloba (and its hydrolyzate), grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes were determined using enzyme-selective probe substrates, and their effect on human P-glycoprotein (Pgp) was determined using a baculovirus expression system by measuring the verapamil-stimulated, vanadate-sensitive ATPase activity. Extracts were analyzed by HPLC to standardize their concentration(s) of constituents associated with the pharmacological activity, and to allow comparison of their effects on P450 and Pgp with literature values. Many of the extracts/constituents exerted > or = 50 % inhibition of P450 activity. These include those from goldenseal (normalized to alkaloid content) inhibiting CYP2C8, CYP2D6, and CYP3A4 at 20 microM, ginkgo inhibiting CYP2C8 at 10 microM, grape seed inhibiting CYP2C9 and CYP3A4 at 10 microM, milk thistle inhibiting CYP2C8 at 10 microM, and ginsenosides F1 and Rh1 (but not ginseng extract) inhibiting CYP3A4 at 10 microM. Goldenseal extracts/constituents (20 microM, particularly hydrastine) and ginsenoside Rh1 stimulated ATPase at about half of the activity of the model substrate, verapamil (20 microM). The data suggest that the clearance of a variety of drugs may be diminished by concomitant use of these herbs via inhibition of P450 enzymes, but less so by Pgp-mediated effects.
Severe Hypernatremia and Hyperosmolality Exacerbated by an Herbal Preparation in a Patient With Diabetic Ketoacidosis.:Clin Pediatr (Phila). 2007 Jun 21;Bhowmick SK, Hundley OT, Rettig KR.University of South Alabama, College of Medicine.
This article reports a case of severe reversible hypernatremia exacerbated by an herbal agent "goldenseal" (Hydrastis canadensis) in an 11-year-old girl with new onset type I diabetes mellitus presented with diabetic ketoacidosis. A literature review is presented and possible mechanism of hypernatremia caused by this herbal preparation is discussed.
Effects of Root Isoquinoline Alkaloids from Hydrastis canadensis on Fusarium oxysporum Isolated from Hydrastis Root Tissue.:J Chem Ecol. 2007 Jun 5;Tims MC, Batista C.Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA
Goldenseal (Hydrastis canadensis L.) is a popular medicinal plant distributed widely in North America. The rhizome, rootlets, and root hairs produce medicinally active alkaloids. Berberine, one of the Hydrastis alkaloids, has shown antifungal activity. The influence of a combination of the major Hydrastis alkaloids on the plant rhizosphere fungal ecology has not been investigated. A bioassay was developed to study the effect of goldenseal isoquinoline alkaloids on three Fusarium isolates, including the two species isolated from Hydrastis rhizosphere. The findings suggest that the Hydrastis root extract influences macroconidia germination, but that only the combined alkaloids-berberine, canadine, and hydrastine-appear to synergistically stimulate production of the mycotoxin zearalenone in the Fusarium oxysporum isolate. The Hydrastis root rhizosphere effect provided a selective advantage to the Fusarium isolates closely associated with the root tissue in comparison with the Fusarium isolate that had never been exposed to Hydrastis.
Supplementation With Goldenseal (Hydrastis canadensis), but not Kava Kava (Piper methysticum), Inhibits Human CYP3A Activity In Vivo.:Clin Pharmacol Ther. 2007 May 9; Gurley BJ, Swain A, Hubbard MA, Hartsfield F, Thaden J, Williams DK, Gentry WB, Tong Y.1Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
The effects of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on human CYP3A activity were evaluated using midazolam (MDZ) as a phenotypic probe. Sixteen healthy volunteers were randomly assigned to receive either goldenseal or kava kava for 14 days. Each supplementation phase was followed by a 30-day washout period. MDZ (8 mg, per os) was administered before and after each phase, and pharmacokinetic parameters were determined using standard non-compartmental methods. Comparisons of pre- and post-supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal (AUC((0-infinity)), 107.9+/-43.3 vs 175.3+/-74.8 ng.h/ml; Cl/F/kg, 1.26+/-0.59 vs 0.81+/-0.45 l/h/kg; T(1/2), 2.01+/-0.42 vs 3.15+/-1.12 h; C(max), 50.6+/-26.9 vs 71.2+/-50.5 ng/ml). MDZ disposition was not affected by kava kava supplementation. These findings suggest that significant herb-drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates.Clinical Pharmacology & Therapeutics advance online publication 9 May 2007; doi:10.1038/sj.clpt.6100222.
Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids.:Anal Chem. 2007 Apr 1;79(7):2778-89. Epub 2007 Mar 6.Van Berkel GJ, Tomkins BA, Kertesz V.Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6131, USA. vanberkelgj@ornl.gov
Desorption electrospray ionization mass spectrometry was investigated as a means to qualitatively identify and to quantify analytes directly from developed normal-phase thin-layer chromatography plates. The atmospheric sampling capillary of a commercial ion trap mass spectrometer was extended to permit sampling and ionization of analytes in bands separated on intact TLC plates (up to 10 cmx10 cm). A surface positioning software package and the appropriate hardware enabled computer-controlled surface scanning along the length of development lanes or at fixed Rf value across the plates versus the stationary desorption electrospray emitter. Goldenseal (Hydrastis canadensis) and related alkaloids and commercial dietary supplements were used as standards and samples. Alkaloid standards and samples were spotted and separated on aluminum- or glass-backed plates using established literature methods. The mass spectral signal levels as a function of desorption spray solvent were investigated with acetonitrile proving superior to methanol. The detection levels (approximately 5 ng each or 14-28 pmol) in mass spectral full-scan mode were determined statistically from the calibration curves (2.5-100 pmol) for the standards berberine, palmatine, and hydrastinine spotted as a mixture and separated on the plates. Qualitative screening of the major alkaloids present in six different over-the-counter "goldenseal" dietary supplements was accomplished by obtaining full-scan mass spectra during surface scans along the development lane in the direction of increasing Rf value. In one sample, alkaloids were detected that strongly suggested the presence of at least one additional herb undeclared on the product label. These same data indicated the misidentification of one of the alkaloids in the TLC literature. Quantities of the alkaloids present in two of the samples determined using the mass spectral data were in reasonable agreement with the label values, indicating the quantitative ability of the method. The advantage of mass spectral measurements in identifying and quantifying materials within overlapping bands and in providing positive identification for even minor species in a mixture was also demonstrated.
Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.:Drug Metab Dispos. 2007 Feb;35(2):240-5. Epub 2006 Nov 1.Gurley BJ, Swain A, Barone GW, Williams DK, Breen P, Yates CR, Stuart LB, Hubbard MA, Tong Y, Cheboyina S.Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, College of Pharmacy, 4301 West Markham Street, Slot 522-3, Little Rock, AR 72205, USA. gurleybillyj@uams.edu
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.
Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects.:Clin Infect Dis. 2006 Oct 15;43(8):1052-9. Epub 2006 Sep 8.Lee LS, Andrade AS, Flexner C.Division of Clinical Pharmacology, Johns Hopkins University, Baltimore, MD, USA.
Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained.
The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.:J Lipid Res. 2006 Oct;47(10):2134-47. Epub 2006 Aug 2.Abidi P, Chen W, Kraemer FB, Li H, Liu J.Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Our previous studies have identified berberine (BBR), an alkaloid isolated from the Chinese herb huanglian, as a unique cholesterol-lowering drug that upregulates hepatic low density lipoprotein receptor (LDLR) expression through a mechanism of mRNA stabilization. Here, we demonstrate that the root extract of goldenseal, a BBR-containing medicinal plant, is highly effective in upregulation of liver LDLR expression in HepG2 cells and in reducing plasma cholesterol and low density lipoprotein cholesterol (LDL-c) in hyperlipidemic hamsters, with greater activities than the pure compound BBR. By conducting bioassay-driven semipurifications, we demonstrate that the higher potency of goldenseal is achieved through concerted actions of multiple bioactive compounds in addition to BBR. We identify canadine (CND) and two other constituents of goldenseal as new upregulators of LDLR expression. We further show that the activity of BBR on LDLR expression is attenuated by multiple drug resistance-1 (MDR1)-mediated efflux from liver cells, whereas CND is resistant to MDR1. This finding defines a molecular mechanism for the higher activity of CND than BBR. We also provide substantial evidence to show that goldenseal contains natural MDR1 antagonist(s) that accentuate the upregulatory effect of BBR on LDLR mRNA expression. These new findings identify goldenseal as a natural LDL-c-lowering agent, and our studies provide a molecular basis for the mechanisms of action.
Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.). 2. Palmatine, hydrastine, canadine, and hydrastinine.:Chem Res Toxicol. 2006 Jun;19(6):739-44.Inbaraj JJ, Kukielczak BM, Bilski P, He YY, Sik RH, Chignell CF.Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Goldenseal is an herb that is widely used in dietary supplements, eye washes, and skin lotions. The presence of Goldenseal root powder in dietary supplements and the topical application of Goldenseal preparations raise the possibility that an adverse phototoxic reaction may result from an interaction between its constituent alkaloids and light in exposed tissues. We have previously shown that berberine, the major alkaloid in Goldenseal powder, in combination with UVA causes DNA damage and cell death in HaCaT keratinocytes [(2001) Chem. Res. Toxicol. 14, 1529]. We have studied the photochemical and photobiological properties of four minor alkaloids found in Goldenseal, namely, hydrastine, palmatine, canadine, and hydrastinine. UVA radiation of palmatine in aqueous solutions generated no (1)O(2), but in CH(2)Cl(2), copious amounts of (1)O(2) were detected (Phi = 0.2). Palmatine also photogenerated oxygen-centered radicals, (*)OH and O(2)(*)(-) in aerated aqueous buffer and acetonitrile, respectively, as detected by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In nitrogen-sparged acetonitrile containing DMPO, we observed the neutral palmatine radical formed by one-electron reduction. UVA irradiation (4 J/cm(2)) of HaCaT keratinocytes in the presence of palmatine (50 microM) resulted in a 50% decrease in cell viability but no DNA damage as measured by the comet assay. UVA irradiation of hydrastine, hydrastinine, or canadine (50 microM) did not cause DNA damage or cell death in keratinocytes. Although palmatine is photoactive, it is present in such small amounts in Goldenseal root powder that the phototoxicity of the herb is most likely due to berberine, the major constituent alkaloid.
Developmental toxicity evaluation of berberine in rats and mice.:Birth Defects Res B Dev Reprod Toxicol. 2006 Jun;77(3):195-206.Jahnke GD, Price CJ, Marr MC, Myers CB, George JD.Sciences International Inc., Research Triangle Park, North Carolina 27709, USA. Janke@niehs.nih.gov
BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3,625, 7,250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3,500, 5,250, or 7,000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1,313 mg/kg/day (rats) and 0, 569, 841, and 1,155 mg/kg/day (mice). RESULTS: There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7,250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5,250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1,000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7,250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1,000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5,250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1,000 mg/kg/day BCD based on decreased fetal body weight.
Metal content of ephedra-containing dietary supplements and select botanicals.:Am J Health Syst Pharm. 2006 Apr 1;63(7):635-44.Grippo AA, Hamilton B, Hannigan R, Gurley BJ.Department of Chemistry and Physics, Arkansas State University, PO Box 599, State University, AR 72467, USA. agrippo@astate.edu
PURPOSE: The metal content of dietary supplements, including 13 ephedra-containing supplements, was studied. METHODS: Samples of botanicals (black cohosh, echinacea, goldenseal, kava kava, milk thistle, saw palmetto, Synephrine, and valerian root), ephedra-containing dietary supplements (Amp II, EPH 833, Ephedra, Ephedra 1000, Hydroxycut, Metabolife 356, Metabolift, Ripped Fuel, Ripped Fuel Extreme, Ripped Fuel [ma huang-free], Stacker 2 [two lots], Super Stinger, Virgin Earth, Xenadrine RFA-1 [two lots], Yellow Jacket), and nonprescription reference agents (NoDoz and Primatene) were digested in acid, reacidified, and then spiked with internal standards. Metals were quantified using Environmental Protection Agency quality assurance and quality-control standards 6020 and 200.8. Forty-seven metals were analyzed by inductively coupled plasma-mass spectrometry, with subpart-per-trillion detection limits. RESULTS: All metals detected were in concentrations below toxic levels or physiological limit levels for the daily doses specified by the products' labeling. Metals found in highest concentrations among all the supplements sampled were sodium, magnesium, calcium, potassium, aluminum, iron, titanium, mercury, strontium, lead, barium, and silver. Of the 27 supplements analyzed, those with the lowest metal concentrations were mostly single-ingredient botanical supplements, while multiple-component, ephedra-containing dietary supplements generally had higher metal concentrations. Significant lot-to-lot variations were found for two ephedra-containing dietary supplements. CONCLUSION: None of 47 metals was found in highly toxic amounts in 23 brands of dietary supplements and two nonprescription reference preparations.
Top-10 list of herbal and supplemental medicines used by cosmetic patients: what the plastic surgeon needs to know.:Plast Reconstr Surg. 2006 Feb;117(2):436-45; discussion 446-7.Heller J, Gabbay JS, Ghadjar K, Jourabchi M, O'Hara C, Heller M, Bradley JP.Division of Plastic and Reconstructive Surgery, University of California, Los Angeles, California 90069, USA.
BACKGROUND: Widespread use of herbal medications/supplements among the presurgical population may have a negative effect on perioperative patient care. Thus, the authors' goal was to identify the prevalence of such use in a cosmetic surgery patient population compared with use among the general public; to assess physician awareness of proper management of these herbal medications/supplements; and to review the literature to provide rational strategies for managing perioperative patients taking these remedies. METHODS: To assess patient (n = 100) and general public (n = 100) usage rates, open-ended lists of (1) the most common herbal medications/supplements and (2) homeopathic treatments were compiled. Board-certified plastic surgeons (n = 20) were then given the same list of herbs/supplements and surveyed on their awareness of these treatments and perioperative side effects. RESULTS: The usage rate for cosmetic versus public surveys for herbal medicines/supplements was 55 percent versus 24 percent (p < 0.001), with 35 percent versus 8 percent (p < 0.001) engaging in homeopathic practices, respectively. Cosmetic patients' top four herbal/supplements of usage were chondroitin (18 percent), ephedra (18 percent), echinacea (14 percent), and glucosamine (10 percent). The top four used by the general public were echinacea (8 percent), garlic (6 percent), ginseng (4 percent), and ginger (4 percent). The physician survey demonstrated awareness of 54 percent of the listed supplements/herbal medicines, 85 percent of which were not suggested to be discontinued preoperatively, with only ephedra achieving 100 percent physician discontinuation preoperatively. CONCLUSIONS: Herbal medicines and supplements displayed greater prevalence in the cosmetic surgery population than in the population at large. Furthermore, side effects and potential complications warrant addressing these remedies as pharmaceuticals rather than as safe and "natural." Thus, a descriptive "top-10" list with perioperative recommendations was compiled for the plastic surgeon.
A reproductive screening test of goldenseal.:Birth Defects Res B Dev Reprod Toxicol. 2005 Oct;74(5):399-404.Yao M, Ritchie HE, Brown-Woodman PD.School of Biomedical Sciences, Faculty of Health Sciences, The University of Sydney, Lidcombe, Australia.
BACKGROUND: Goldenseal (Hydrastis canadensis L) is a multi-purpose herb (Hobbs, 1990: Pharm Hist 32:79-82) widely used for its antibiotic properties. It is traditionally contraindicated in pregnancy based on in vivo data but this contraindication has not been confirmed by conventional studies that have been peer reviewed. METHODS: Female rats were dosed by gavage using 65 times the human dose of goldenseal daily on either gestation days (GD) 1-8 or GD 8-15. Controls received an equivalent dose of ethanol. On GD 20, fetuses were weighed and examined for signs of external, internal, or skeletal malformations. Rat fetuses were also explanted on GD 10.5 and cultured with decreasing concentrations of goldenseal for 26 hr. Embryos were examined for growth retardation and malformations. RESULTS: There was no increase in pre- or post-implantation losses. There was no increase in fetal body weight in fetuses exposed to goldenseal. There was no difference in incidence of external or internal malformations. Goldenseal induced toxicity when GD10.5 embryos were cultured for 26 hr in rat serum to which extract was added. CONCLUSIONS: It is likely that poor absorption of goldenseal from the small intestine could explain the discrepancy between the in vivo and in vitro results. It is unlikely that serum concentration from oral treatment could attain the LOEL achieved in vitro. The contrasting results highlight the continuing importance of in vivo work and the necessity of pharmacokinetic data when interpreting in vitro data. The data suggest that goldenseal, at the prescribed human dose, is unlikely to be absorbed to an extent to be unsafe to use in pregnancy despite the apparent cytotoxic effects in vitro. However, these results indicate that pharmacokinetic studies are required to confirm this conclusion.
Extraction and HPLC analysis of alkaloids in goldenseal.:Sheng Wu Gong Cheng Xue Bao. 2004 Mar;20(2):306-8. Chinese.Weber HA, Joseph M.Midwest Research Institute 425 Volker Blvd Kansas City, MO 64110, USA.
An ambient extraction of goldenseal root powder followed by HPLC analysis of the alkaloids on a Zorbax Rapid Resolution Eclipse XDB-C18 column provides an accurate method for the determination of key alkaloids in goldenseal, including berberine and hydrastine. The extraction and HPLC analysis can be applied to several other alkaloids, including canadine, hydrastinine, and palmatine, and may be applicable to other berberine-containing plant roots. The Rapid Resolution Eclipse XDB-C18 column is used for an isocratic separation with high resolution of all componentsin under 15 minutes.
Capillary zone electrophoresis as a tool for the quality control of goldenseal extracts.:Electrophoresis. 2005 Jun;26(12):2430-6.Unger M, Laug S, Holzgrabe U.Institute of Pharmacy and Food Chemistry, Julius Maximilians-University, Würzburg, Germany. m.unger@pzlc.uni-wuerzburg.de
The root extracts of goldenseal (Hydrastis canadensis L.) are popular phytomedicines for the treatment of gastrointestinal disorders and upper respiratory tract infections. Here we describe a simple and fast capillary zone electrophoresis (CZE) method with ultraviolet detection at 225 nm for the quantification of the major goldenseal constituents, berberine and hydrastine, in herbal remedies containing goldenseal root extracts. Tritoqualine, an antihistaminic drug with a hydrastine-like phthalidisoquinoline structure, was applied as an internal standard. The running buffer was a 1:5 mixture of 500 mM ammonium acetate (adjusted to pH 3.4 with acetic acid) and methanol. Our newly developed CZE method was validated regarding limit of detection (LOD), limit of quantification, linearity, accuracy and precision. For both berberine and hydrastine, the LOD was 1.0 microg/mL and the linearity was obtained between 2.5 and 500 microg/mL. Using our newly developed method, both the alkaloids could be analysed in herbal remedies containing goldenseal root extracts within 8 min.
In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.:Clin Pharmacol Ther. 2005 May;77(5):415-26. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A.Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 522, Little Rock, AR 72205, USA.
OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. METHODS: Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic ratios were observed for valerian. CONCLUSIONS: Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, whereas kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Accordingly, serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively. Valerian appears to be less likely to produce CYP-mediated herb-drug interactions.
Natural health product-HIV drug interactions: a systematic review.:Int J STD AIDS. 2005 Mar;16(3):181-6.Mills E, Montori V, Perri D, Phillips E, Koren G.Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON L8N 3Z5, Canada. millsej@mcmaster.ca
The use of natural health products (NHPs) within the HIV community is high. Several NHPs have demonstrated interactions with HIV medications that could contribute to drug failure. We aimed to conduct a systematic review of clinical trials examining NHP-HIV drug interactions and their methodological characteristics. We searched electronic databases and unpublished resources independently, in duplicate. Nine studies were identified, eight clinical pharmacokinetics trials and one population-pharmacokinetics trial. Investigators studied four different herbal medicines (St John's wort, garlic, goldenseal and milk thistle) and one vitamin (vitamin C). Significant interactions were observed with St John's wort, garlic and vitamin C. However, methodological challenges exist to making the results directly generalizable to patients. This review finds that important drug level changes exist when NHPs are combined with HIV medications. Considering patient values and the implications of these studies, further research is urgently required to determine the extent of interactions with other commonly used NHPs.
A new glucosyl feruloyl quinic acid as a potential marker for roots and rhizomes of goldenseal, Hydrastis canadensis.:J Nat Prod. 2004 Nov;67(11):1818-22.McNamara CE, Perry NB, Follett JM, Parmenter GA, Douglas JA.New Zealand Institute for Crop & Food Research Limited, Plant Extracts Research Unit, Department of Chemistry, University of Otago, Box 56, Dunedin, New Zealand.
A new compound, 5-O-(4'-[beta-d-glucopyranosyl]-trans-feruloyl)quinic acid (GPFQ, 10), is reported from the medicinal plant goldenseal (Hydrastis canadensis). A new HPLC method is described and used to show that GPFQ is a potential marker for goldenseal roots (1.0% w/w) and rhizomes (2.3%). GPFQ was found at much lower levels in stems (<0.1%) and could not be detected in leaves. Neochlorogenic acid (9), which has not previously been reported from goldenseal, and chlorogenic acid (6) reached their highest levels in leaves (0.9% 9 and 0.5% 6). The main alkaloids, hydrastine (1) and berberine (2), were highest in rhizomes (2.8% 1 and 4.6% 2), but palmatine (5) was not found in genuine goldenseal.
Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen.:J Toxicol Clin Toxicol. 2003;41(6):865-7.Palanisamy A, Haller C, Olson KR.School of Medicine, University of California, San Francisco, California, USA.
Photosensitivity, an abnormal skin reaction to light, is a rare adverse event associated with herbal medicine use. Case reports in the literature most commonly implicate St. John's wort. In this report, we describe the case of a 32-year-old woman who suffered a phototoxic reaction after taking a dietary supplement containing ginseng, goldenseal, bee pollen, and other ingredients. On presentation, she had a pruritic, erythematous rash, localized to the sun-exposed surfaces of her neck and extremities. She had no significant past medical history and was not taking any other medications. The skin rash slowly resolved after discontinuation of the supplement and with treatment including subcutaneous and topical corticosteroids. Although the individual ingredients in this dietary supplement have not been associated with cases of photosensitivity, it is possible that the combination of ingredients may have interacted to cause this toxic reaction. Therefore, we recommend caution in the combining of multiple herbs and supplements into new formulations.
Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers.:J Agric Food Chem. 2003 Dec 3;51(25):7352-8.Weber HA, Zart MK, Hodges AE, Molloy HM, O'Brien BM, Moody LA, Clark AP, Harris RK, Overstreet JD, Smith CS.Midwest Research Institute, 425 Volker Boulevard, Kansas City, Missouri 64110. hweber@mriresearch.org
The characterization of herbal materials is a significant challenge to analytical chemists. Goldenseal (Hydrastis canadensis L.), which has been chosen for toxicity evaluation by NIEHS, is among the top 15 herbal supplements currently on the market and contains a complex mixture of indigenous components ranging from carbohydrates and amino acids to isoquinoline alkaloids. One key component of herbal supplement production is botanical authentication, which is also recommended prior to initiation of efficacy or toxicological studies. To evaluate material available to consumers, goldenseal root powder was obtained from three commercial suppliers and a strategy was developed for characterization and comparison that included Soxhlet extraction, HPLC, GC-MS, and LC-MS analyses. HPLC was used to determine the weight percentages of the goldenseal alkaloids berberine, hydrastine, and canadine in the various extract residues. Palmatine, an isoquinoline alkaloid native to Coptis spp. and other common goldenseal adulterants, was also quantitated using HPLC. GC-MS was used to identify non-alkaloid constituents in goldenseal root powder, whereas LC-MS was used to identify alkaloid components. After review of the characterization data, it was determined that alkaloid content was the best biomarker for goldenseal. A 20-min ambient extraction method for the determination of alkaloid content was also developed and used to analyze the commercial material. All three lots of purchased material contained goldenseal alkaloids hydrastinine, berberastine, tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine. Material from a single supplier also contained palmatine, coptisine, and jatrorrhizine, thus indicating that the material was not pure goldenseal. Comparative data for three commercial sources of goldenseal root powder are presented.
Variations in product choices of frequently purchased herbs: caveat emptor.:Arch Intern Med. 2003 Oct 27;163(19):2290-5.Garrard J, Harms S, Eberly LE, Matiak A.Divisions of Health Services Research & Policy, School of Public Health, and College of Pharmacy, University of Minnesota, Minneapolis 55455, USA. jgarrard@umn.edu
BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.
Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components.:Drug Metab Dispos. 2003 Nov;31(11):1391-7.Chatterjee P, Franklin MR.Department of Pharmacology & Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112-5820, USA.
The concurrent use of herbal medicinals with prescription and over-the-counter drugs carries a risk for unanticipated adverse drug-botanical pharmacokinetic interactions, particularly as a result of cytochrome P450 (P450) inhibition. Extracts of goldenseal (Hydrastis canadensis) containing approximately equal concentrations ( approximately 17 mM) of two methylenedioxyphenyl alkaloids, berberine and hydrastine, inhibited with increasing potency (CYP2C9) diclofenac 4'-hydroxylation, (CYP2D6) bufuralol 1'-hydroxylation, and (CYP3A4) testosterone 6beta-hydroxylation activities in human hepatic microsomes. The inhibition of testosterone 6beta-hydroxylation activity was noncompetitive with an apparent Ki of 0.11% extract. Of the methylenedioxyphenyl alkaloids, berberine (IC50 = 45 microM) was the more inhibitory toward bufuralol 1'-hydroxylation and hydrastine (IC50 approximately 350 microM for both isomers), toward diclofenac 4'-hydroxylation. For testosterone 6beta-hydroxylation, berberine was the least inhibitory component (IC50 approximately 400 microM). Hydrastine inhibited testosterone 6beta-hydroxylation with IC50 values for the (+)- and (-)-isomers of 25 and 30 microM, respectively. For (-)-hydrastine, an apparent Ki value of 18 microM without preincubation and an NADPH-dependent mechanism-based inhibition with a kinactivation of 0.23 min(-1) and a KI of approximately 110 microM were determined. Cytochrome P450 metabolic-intermediate (MI) complex formation could be demonstrated for both hydrastine isomers. With expressed P450 isoforms, hydrastine formed a P450 MI complex with CYP2C9, CYP2D6, and CYP3A4. Coexpression of cytochrome b5 with the P450 isoforms enhanced the rate but not the extent of P450 MI complex formation.
Influence of goldenseal root on the pharmacokinetics of indinavir.:J Clin Pharmacol. 2003 Nov;43(11):1283-8.Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ.Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI, USA.
Goldenseal root was identified as the most potent inhibitor of CYP3A4 in a study that tested 21 popular herbal products for in vitro inhibitory activity. The purpose of this investigation was to examine the influence of goldenseal root on the disposition of the CYP3A4 substrate indinavir in humans. Using a crossover study design, the pharmacokinetics of indinavir were characterized in 10 healthy volunteers before and after 14 days of treatment with goldenseal root (1140 mg twice daily). Indinavir was given as a single 800-mg oral dose, and blood samples were collected for 8 hours following the dose. No statistically significant differences in peak concentration (11.6 vs. 11.9 mg/L) or oral clearance (26.8 vs. 23.9 mg*h/L) were observed following treatment with goldenseal root. Half-life and time to reach peak concentration were also unchanged by goldenseal. These results suggest that patients being treated with indinavir can safely take goldenseal root and that interactions with other drugs metabolized by CYP3A4 in the liver are unlikely.
Antimicrobial constituents from goldenseal (the Rhizomes of Hydrastis canadensis) against selected oral pathogens.:Planta Med. 2003 Jul;69(7):623-7.Hwang BY, Roberts SK, Chadwick LR, Wu CD, Kinghorn AD.Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Two new C-methyl flavonoids, 6,8-di- C-methylluteolin 7-methyl ether (1) and 6- C-methylluteolin 7-methyl ether (2), were isolated from a commercially available sample of the roots of Hydrastis canadensis, along with seven known compounds, berberine (3), beta-hydrastine (4), canadine (5), canadaline (6), isocorypalmine (7), canadinic acid (8), and beta-sitosterol 3- O-beta- D-glucoside (9). The structures of the new compounds 1 and 2 were elucidated on the basis of their spectral data including 1D and 2D NMR techniques. Of these isolates, berberine (3) and, to a lesser extent, 1 and 2, showed antimicrobial activity when evaluated against the oral pathogens Streptococcus mutans and Fusobacterium nucleatum. Berberine (3) exhibited an additive antimicrobial effect when tested against S. mutans in combination with 1.
Method validation for determination of alkaloid content in goldenseal root powder.:J AOAC Int. 2003 May-Jun;86(3):476-83.Weber HA, Zart MK, Hodges AE, White KD, Barnes SM, Moody LA, Clark AP, Harris RK, Overstreet JD, Smith CS.Midwest Research Institute, 425 Volker Blvd, Kansas City, MO 64110, USA. hweber@mriresearch.org
A fast, practical ambient extraction methodology followed by isocratic liquid chromatography (LC) analysis with UV detection was validated for the determination of berberine, hydrastine, and canadine in goldenseal (Hydrastis canadensis L.) root powder. The method was also validated for palmatine, a major alkaloid present in the possible bioadulterants Coptis, Oregon grape root, and barberry bark. Alkaloid standard solutions were linear over the evaluated concentration ranges. The analytical method was linear for alkaloid extraction using 0.3-2 g goldenseal root powder/100 mL extraction solvent. Precision of the method was demonstrated using 10 replicate extractions of 0.5 g goldenseal root powder, with percent relative standard deviation for all 4 alkaloids < or = 1.6. Alkaloid recovery was determined by spiking each alkaloid into triplicate aliquots of neat goldenseal root powder. Recoveries ranged from 92.3% for palmatine to 101.9% for hydrastine. Ruggedness of the method was evaluated by performing multiple analyses of goldenseal root powder from 3 suppliers over a 2-year period. The method was also used to analyze Coptis root, Oregon grape root, barberry bark, and celandine herb, which are possible goldenseal bioadulterants. The resulting chromatographic profiles of the bioadulterants were significantly different from that of goldenseal. The method was directly transferred to LC with mass spectrometry, which was used to confirm the presence of goldenseal alkaloids tetrahydroberberastine, berberastine, canadaline, berberine, hydrastine, and canadine, as well as alkaloids from the bioadulterants, including palmatine, jatrorrhizine, and coptisine.
Variations in alkaloid content of herbal products containing goldenseal.:J Am Pharm Assoc (2003). 2003 May-Jun;43(3):419-23.Edwards DJ, Draper EJ.Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Mich 48201, USA. dje@wayne.edu
OBJECTIVE: To determine the concentration of hydrastine and berberine, the primary alkaloids in herbal products containing goldenseal. DESIGN: Descriptive comparison of 20 products purchased at local pharmacies or health food stores; 17 products were labeled as containing goldenseal root and 3 products contained goldenseal herb as the sole active herbal ingredient. SETTING: Laboratory assessment of alkaloid content using high-performance liquid chromatography. MAIN OUTCOME MEASURES: Comparisons of hydrastine and berberine concentration, alkaloid ratio, and total alkaloid content among products. RESULTS: Hydrastine concentration in products labeled as containing goldenseal root ranged from 0 to 2.93%, whereas berberine concentration varied from 0.82% to 5.86%. Median total alkaloid concentration was 5.30%. Only 10 of 17 products met proposed United States Pharmacopeia (USP) standards for the hydrastine and berberine content of goldenseal root. Five products contained little or no hydrastine, unusual berberine:hydrastine ratios, and additional peaks not observed with other products. Alkaloid content in goldenseal root products was about fourfold higher than in products labeled as containing goldenseal herb. CONCLUSION: Alkaloid content of goldenseal products varies widely, with many products failing to meet proposed USP standards. In addition, the chromatographic pattern and alkaloid ratio for several products were atypical for goldenseal. Given the current absence of regulation of the quality of herbal products, pharmacists should take extra care to ensure that substandard goldenseal products are not sold in their pharmacies.
Microbial transformation of the phthalideisoquinoline alkaloid, (-)-beta-hydrastine.:Nat Prod Res. 2003 Aug;17(4):269-74.Herath WH, Ferreira D, Khan IA.National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, USA.
The phthalideisoquinoline alkaloid (-)-beta-hydrastine is one of the main active constituents of the medicinal plant, Hydrastis canadensis, which is used in many dietary supplements intended to enhance the immune system. Treatment of hydrastine with the fermentation broth of Polyporous brumalis (ATCC 34487) as a model for mammalian metabolism, gave a new alkaloid, (1S)-hydroxyhydrastine. Structure elucidation was based primarily on NMR and chiroptical studies.
In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products.:Phytomedicine. 2003 May;10(4):334-42.Foster BC, Vandenhoek S, Hana J, Krantis A, Akhtar MH, Bryan M, Budzinski JW, Ramputh A, Arnason JT.Office of Science, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada. brian_foster@hc-sc.gc.ca
Spices, herbal and black teas, and soybean products were analyzed for their capacity to inhibit in vitro metabolism of drug marker substrates by human cytochrome P-450 (CYP) isoforms. Inhibition of drug metabolism was determined using aliquots or infusions from these products in a fluorescence-detection assay. Aliquots and infusions of all natural product categories inhibited 3A4 metabolism to some extent. Of the 26 aliquots from teas and spices further tested with 2C9, 2C19 and 2D6, many demonstrated significant inhibitory activity on the metabolism mediated by these isoforms. Black teas and herbal tea mixtures were generally more inhibitory than single-entity herbal teas. Spices and single-entity herbal teas showed species-specific isoform inhibition with sage, thyme, cloves, St John's Wort and goldenseal having the highest activity against several isoforms. Seven soybean varieties tested, as well as daidzein and genistein isolated from soybean, were found to inhibit 3A4-mediated metabolism. Genistein was found to inhibit 3A7- but not 3A5-mediated metabolism of the marker substrate. Assessment of the in vitro CYP inhibition potential for these natural products has important implications for predicting the likelihood of natural product-drug interactions if these products are taken concomitantly.
In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis.:Phytother Res. 2003 Mar;17(3):217-21.Mahady GB, Pendland SL, Stoia A, Chadwick LR.Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA. mahady@uic.edu
Methanol extracts of the rhizomes of Sanguinaria canadensis, and the roots and rhizomes of Hydrastis canadensis, two plants used traditionally for the treatment of gastrointestinal ailments, were screened for in vitro antibacterial activity against 15 strains of Helicobacter pylori. The rhizome extracts, as well as a methanol extract of S. canadensis suspension-cell cultures inhibited the growth of H. pylori in vitro, with a MIC50 range of 12.5-50.0 microg/ml. Three isoquinoline alkaloids were identified in the active fraction. Sanguinarine and chelerythrine, two benzophenanthridine alkaloids, inhibited the growth of the bacterium, with an MIC50 of 50.0 and 100.0 microg/ml, respectively. Protopine, a protopine alkaloid, also inhibited the growth of the bacterium, with a MIC50 of 100 microg/ml. The crude methanol extract of H. canadensis rhizomes was very active, with an MIC50 of 12.5 microg/ml. Two isoquinoline alkaloids, berberine and beta-hydrastine, were identified as the active constituents, and having an MIC50 of 12.5 and 100.0 microg/ml, respectively.
Micropropagation of Hydrastis canadensis: Goldenseal a North American endangered species.:Planta Med. 2003 Jan;69(1):86-8. Bedir E, Lata H, Schaneberg B, Khan IA, Moraes RM.
An in vitro propagation protocol for rapidly producing Hydrastis canadensis L., Goldenseal, plantlets from disk tissue of young leaves was developed. Leaf explants were inoculated on MS medium supplemented with various concentrations of NAA and TDZ for production of callus. Two-month-old calli were sub-cultured on MS media containing cytokinins (BA, kinetin, TDZ) in different concentrations for shoot initiation. The optimum level of callus induction and maintenance was in 5.3 microM NAA in combination with 2.2 microM of TDZ. Shoot multiplication was achieved on MS medium with 2.2 microM TDZ in combination with 0.5 microM NAA. The alkaloid profile of micropropagated plantlets was similar to the profile of the mother plants. These results suggest that our in vitro propagation protocol will produce a positive impact in the conservation of H. canadensis.
Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model.:Biol Pharm Bull. 2003 Jan;26(1):110-1.
The effects of berberine in senescence accelerated mice P6 (SAMP6) were investigated to learn whether the alkaloid affects bone mineral density (BMD). Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.
An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events.:Adverse Drug React Toxicol Rev. 2002;21(3):143-50. Review.Haller CA, Anderson IB, Kim SY, Blanc PD.Department of Medicine and Clinical Pharmacy, University of California, San Francisco, California, USA. dchaller@worldnet.att.net
OBJECTIVE: There has been a recent proliferation of medical reference texts intended to guide practitioners whose patients use herbal therapies. We systematically assessed six herbal reference texts to evaluate the information they contain on herbal toxicity. METHODS: We selected six major herbal references published from 1996 to 2000 to evaluate the adequacy of their toxicological information in light of published adverse events. To identify herbs most relevant to toxicology, we reviewed herbal-related calls to our regional California Poison Control System, San Francisco division (CPCS-SF) in 1998 and identified the 12 herbs (defined as botanical dietary supplements) most frequently involved in these CPCS-SF referrals. We searched Medline (1966 to 2000) to identify published reports of adverse effects potentially related to these same 12 herbs. We scored each herbal reference text on the basis of information inclusiveness for the target 12 herbs, with a maximal overall score of 3. RESULTS: The herbs, identified on the basis of CPCS-SF call frequency were: St John's wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe and kava kava. The overall herbal reference scores ranged from 2.2 to 0.4 (median 1.1). The Natural Medicines Comprehensive Database received the highest overall score and was the most complete and useful reference source. All of the references, however, lacked sufficient information on management of herbal medicine overdose, and several had incorrect overdose management guidelines that could negatively impact patient care. CONCLUSION: Current herbal reference texts do not contain sufficient information for the assessment and management of adverse health effects of botanical therapies.
A validated high performance liquid chromatographic method for the analysis of Goldenseal.:J Pharm Pharmacol. 2002 Mar;54(3):435-9.Li W, Fitzloff JF.Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Goldenseal (Hydrastis canadensis L.) has emerged as one of the top ten herbal supplements on the worldwide market. A rapid, simple and validated high performance liquid chromatographic method, with photodiode array detection, has been developed for the analysis of commercial Goldenseal products. Samples were treated by sonication with acidified methanol/water. The method was validated for LOD, LOQ, linearity, reproducibility and recovery with good results.
Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine.:Chem Res Toxicol. 2001 Nov;14(11):1529-34.Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF.Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Goldenseal is an herb which is widely used for many medical applications such as in eyewashes and skin lotions and which is currently undergoing testing by the National Toxicology Program. The main alkaloid constituent of Goldenseal is berberine. The topical application of Goldenseal or berberine to the skin or eyes raises the possibility that an adverse phototoxic reaction may result from an interaction between the alkaloid and light. We have therefore studied the photochemistry of berberine in different solvents and its phototoxicty to HaCaT keratinocytes. Irradiation of berberine in aqueous solutions does not generate (1)O(2), but in CH(2)Cl(2), (1)O(2) is produced with a quantum yield phi = 0.34. With the aid of the electron paramagnetic resonance (EPR) spin trapping technique and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we have detected oxygen-centered radicals photogenerated by berberine in water and acetonitrile. In the latter solvent and in the absence of oxygen, the neutral berberine radical formed by one electron reduction was observed. Methanol radicals were detected by EPR in water/alcohol low-temperature glasses irradiated in the berberine long-wavelength absorption band. In such alcoholic glasses, we have also detected an EPR signal from the berberine triplet at 77 K, in contrast to aqueous glasses where neither triplet nor radicals were detectable. Our data show that, although a weak photosensitizer in water, berberine is able to produce both (1)O(2) and radical species in a nonpolar environment. UVA irradiation of HaCaT keratinocytes in the presence of 50 microM berberine resulted in an 80% decrease in cell viability and a 3-fold increase in DNA damage as measured by the Comet assay. These findings suggest that exposure to sunlight or artificial light sources emitting UVA should be avoided when topical preparations derived from Goldenseal or containing berberine are used.
High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal.:J Pharm Sci. 2001 Jul;90(7):817-22.Abourashed EA, Khan IA.National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
Goldenseal (Hydrastis canadensis L., Ranunculaceae) is an ingredient of various dietary supplements intended for enhancing general body immunity. Many goldenseal products are currently available in the United States, either alone or in combination with echinacea. In most products, the content of the main active alkaloids of goldenseal, hydrastine and berberine, is not indicated on the label. A high-performance liquid chromatography (HPLC) method has been developed for the detection and quantification of hydrastine and berberine in a number of products obtained from the United States market. The method uses a Phenomenex Luna C(18) column, a mobile phase consisting of solvent A (100 mM sodium acetate/acetic acid, pH 4.0) and solvent B (acetonitrile/methanol; 90/10, v/v). Elution was run at a flow rate of 1.0 mL/min, with a linear gradient of 80- 40% A in B over 20 min and ultraviolet detection at 290 nm. A wide range of content variation was observed for both alkaloids in the tested samples.
Relaxant effects of Hydrastis canadensis L. and its major alkaloids on guinea pig isolated trachea.:Pharmacol Toxicol. 2000 Nov;87(5):218-22.Abdel-Haq H, Cometa MF, Palmery M, Leone MG, Silvestrini B, Saso L.Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza, Italy.
Hydrastis or goldenseal, one of the most popular medicinal herbs in the U.S.A., is used in mild pathological conditions like cold and flu, based on the pharmacological properties of its active components, berberine (anticholinergic, antisecretory, and antimicrobial) and beta-hydrastine (astringent). We previously reported the relaxant effect of a total ethanolic extract of hydrastis on carbachol precontracted isolated guinea pig trachea, and with the present study, using the same experimental model, we aimed at evaluating the contribution of its major alkaloids, berberine, beta-hydrastine, canadine and canadaline to the total effect. Furthermore, using specific pharmacological tools, like timolol and xanthine amine congener, we attempted to elucidate its mechanism of action. The EC50 of berberine, beta-hydrastine, canadine and canadaline, were 34.2+/-0.6, 72.8+/-0.6, 11.9+/-1.2 and 2.4+/-0.8 microg/ml, respectively. Timolol effectively antagonized the effect of canadine (EC50 = 19.7+/-3.0 microg/ml) and canadaline (EC50 = 17.1+/-1.2 microg/ml) but not that of berberine and beta-hydrastine, while xanthine amine congener antagonized the effect of beta-hydrastine (EC50 = 149.9+/-35.3 microg/ml) and canadaline (EC50 = 26.1+/-3.0 microg/ml) but not that of berberine and canadine. Besides, the hydrastis extract, at concentrations between 0.01 and 0.1 microg/ml, potentiated the relaxant effect of isoprenaline on carbachol-precontracted isolated guinea pig trachea. These data, which are insufficient to draw definite mechanistic conclusions, indicate that the aforementioned alkaloids may act by interacting with adrenergic and adenosinic receptors.
An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures.:Phytomedicine. 2000 Jul;7(4):273-82.Budzinski JW, Foster BC, Vandenhoek S, Arnason JT.Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada.
Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole. Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.
A convenient method for the determination of the quality of goldenseal.:Fitoterapia. 2000 Jun;71(3):232-5.Govindan M, Govindan G.Department of Chemistry, Fitchburg State College, Fitchburg, MA 01420, USA. mgovindan@fsc.edu
Goldenseal (Hydrastis canadensis) has emerged as one of the top five herbal supplements in the world-wide market. A convenient method for the determination of the quality and possible adulteration of goldenseal products is thin-layer chromatography (TLC). TLC analysis of 10 goldenseal samples using two solvent systems and spray reagents was conducted. Five of these samples contained both hydrastine and berberine, four contained berberine and one did not contain either of these alkaloids. These TLC results were verified by HPLC analysis.
Berberine.:Altern Med Rev. 2000 Apr;5(2):175-7.No authors listed
Berberine is a plant alkaloid with a long history of medicinal use in both Ayurvedic and Chinese medicine. It is present in Hydrastis canadensis (goldenseal), Coptis chinensis (Coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). The berberine alkaloid can be found in the roots, rhizomes, and stem bark of the plants. Berberine extracts and decoctions have demonstrated significant antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. Currently, the predominant clinical uses of berberine include bacterial diarrhea, intestinal parasite infections, and ocular trachoma infections.
Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis.:Immunol Lett. 1999 Jun 1;68(2-3):391-5.Rehman J, Dillow JM, Carter SM, Chou J, Le B, Maisel AS.Department of Internal Medicine, Veterans Affairs Medical Center and University of California, San Diego 92161, USA.
A number of immunomodulatory effects have been attributed to the medicinal plants Echinacea angustifolia and Goldenseal (Hydrastis canadensis); however, little is known about whether treatment with these plants can enhance antigen-specific immunity. We investigated the antigen-specific in vivo immunomodulatory potential of continuous treatment with Echinacea and Goldenseal root extract over a period of 6 weeks using rats that were injected with the novel antigen keyhole limpet hemocyanin (KLH) and re-exposed to KLH after the initial exposure. Immunoglobulin production was monitored via ELISA continuously over a period of 6 weeks. The Echinacea-treated group showed a significant augmentation of their primary and secondary IgG response to the antigen, whereas the Goldenseal-treated group showed an increase in the primary IgM response during the first 2 weeks of treatment. Our results suggest that medicinal plants like Echinacea or Goldenseal may enhance immune function by increasing antigen-specific immunoglobulin production.
Gold in goldenseal.:Hosp Health Netw. 1997 Oct 20;71(20):50-2.Blecher MB, Douglass K.
Healing herbs and alternative therapies already represent a market as big as $40 billion a year--with consumers paying most of the tab. That's why hospitals and entrepreneurs aren't waiting for insurers to expand coverage before venturing into alternative medicine.
Herbal preparation use among urban emergency department patients.:Acad Emerg Med. 1997 Mar;4(3):209-13.Hung OL, Shih RD, Chiang WK, Nelson LS, Hoffman RS, Goldfrank LR.Department of Emergency Medicine, New York University Medical Center, Bellevue Hospital Center, New York, USA. olhung@mnt.po.com
OBJECTIVE: To determine the prevalence of herbal preparation use among patients presenting to an urban teaching hospital ED. METHODS: A prospective anonymous survey on herbal preparation use was performed. Consecutive, acutely ill or injured adult (> or = 18 years old) ED patients were offered the survey over a 1-month period. The survey also asked for information related to patient age, ethnicity, gender, employment, education, cigarette smoking history, ethanol consumption, use of illicit drugs, chief complaint, and HIV status. RESULTS: Of 2,473 eligible subjects, 623 (25%) participated. The overall reported prevalence of herbal preparation use among the participants was 21.7%. Women were more likely to use herbal preparations than men (28.5% vs 17.2%, p = 0.013). Prevalence rates in different ethnic populations were: whites, 18.2%; Hispanics, 13.9%; blacks, 26.4%; and Asians, 36.8%. Asians had a significantly higher use rate than the other ethnic groups (p = 0.039). Neither HIV positivity, educational level, employment status, nor age was significantly associated with herbal preparation use. The most commonly reported herbal preparations were goldenseal tea, garlic, and ginger. Several of the herbal preparations reported as used by patients in this study have been associated with severe systemic toxicity in the medical literature. CONCLUSION: Although the survey response rate was low, the prevalence of herbal preparation use among acutely ill or injured patients presenting to this urban ED remains significant. A directed history toward specific herbal preparation use may provide relevant pharmacologic information and uncover cases of herbal-preparation-induced toxicity.
Reference:
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- 1.Goldenseal Root,Echinacea's partner, broad-spectrum herbs and its uses.
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