Goldenseal and Detoxification
Goldenseal (Hydrastis canadensis L.) is commonly used to self-treat various health conditions such as the common cold, upper respiratory tract infections, gastrointestinal issues, and menstrual disorders. Along with other botanicals, goldenseal is often taken in combination with prescription medications without considering potential interactions or effects on detoxification processes. Goldenseal contains berberine and B-hydrastine, both known as Isoquinoline alkaloids, which are the primary studied active compounds in the herb. These alkaloids possess methylenedioxylphyl rings that can inactivate certain CYP450 enzymes involved in phase 1 detoxification by forming metabolic intermediates (4).
In an in vitro experiment on liver microsomes, McDonald (2020) found that berberine inhibited CYP2D2, CYP3A4/5, while B-hydrastine inhibited CYP2C9, CYP2D6, and CYP3A4/5. An in-vivo study conducted by Gurley (2005) on six women revealed that goldenseal root extract, taken at 900mg, three times a day for 28 days, reduced CYP2D2 by approximately 40% and CYP3A4/5 by a similar percentage. This reduction was the most significant among all the herbs tested, which included kava, black cohosh, and valerian.
Understanding how herbs interact with drug detoxification pathways is crucial. Goldenseal was studied to determine its potential interaction with the drug transporter p-glycoprotein using the substrate digoxin, and while some interaction was observed, it wasn't as significant as initially hypothesized (3). Berberine, an active alkaloid in goldenseal, is a known substrate for p-glycoprotein in vitro (5). CYP3A4, which was affected by goldenseal in the McDonald (2020) study, is an essential enzyme in the detoxification of xenobiotics and is responsible for metabolizing about 50% of orally administered drugs (1).
The inhibition of Phase 1 detoxification by goldenseal can have both beneficial and detrimental effects, depending on the situation and the compound involved. In a study by Yamaura (2011), it was found that acetaminophen, a commonly used NSAID, produces a toxic intermediate, NAPQI, through Phase 1 detoxification, leading to approximately 400-500 deaths per year due to liver failure. The authors tested goldenseal at doses of 300mg/kg and 1000mg/kg 2, 18, and 26 hours after administering 400mg/kg of acetaminophen. The results indicated that goldenseal inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A, with CYP2E1 being the most strongly affected, resulting in reduced bioaccumulation of the toxic intermediate of acetaminophen. This suggests that goldenseal may have hepatoprotective effects against acetaminophen overdose.
References:
Budzinski, J. W., Trudeau, V. L., Drouin, C. E., Panahi, M., Arnason, J. T., & Foster, B. C. (2007). Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Canadian Journal of Physiology and Pharmacology, 85(9), 966–978. https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=18066144&site=eds-live&scope=site
2. Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Khan, I. A., & Shah, A. (2005). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clinical pharmacology and therapeutics, 77(5), 415–426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894911/
3. Gurley, B. J., Swain, A., Barone, G. W., Williams, D. K., Breen, P., Yates, C. R., Stuart, L. B., Hubbard, M. A., Tong, Y., & Cheboyina, S. (2007). Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans. Drug metabolism and disposition: the biological fate of chemicals, 35(2), 240–245.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868501/
4. McDonald, M. G., Tian, D. D., Thummel, K. E., Paine, M. F., & Rettie, A. E. (2020). Modulation of Major Human Liver Microsomal Cytochromes P450 by Component Alkaloids of Goldenseal: Time-Dependent Inhibition and Allosteric Effects. Drug metabolism and disposition: the biological fate of chemicals, 48(10), 1018–1027. https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=32591416&site=eds-live&scope=site
5. Zhang, X., Qiu, F., Jiang, J., Gao, C., & Tan, Y. (2011). Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein. Xenobiotica, 41(4), 290–296. https://uws.idm.oclc.org/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=59402028&site=eds-live&scope=site
