H. canadensis (goldenseal or Golden Seal, a perennial of the buttercup family), otherwise known as: yellow root, orange root, puccoon, ground raspberry or wild curcuma has been an important herbal medicine since settlers learned of it from Native Americans who used it for many purposes including:for mucosal infections, for colds or flu, for dyspepsia or vomiting, for a laxative, for the treatment of hemorrhoids and many others uses. In 1905 when the US Department of Agriculture published a bulletin highlighting its increase usage as a n herbal in America. Nowadays, it is still a popular herbal; it has recently been listed as one of the top 5 selling herbals. It contains many alkaloids: especially hydrastine, berberine, canadine, and others. Interestingly, it has been used to mask urine drug screening for marijuana. In the past, clinical studies have been shown it to be a mild ABCB1 inhibitor (inhibiting digoxin 14%). It also is known to inhibit midazolam but not indinavir- raising the possibility of it being only an intestinalCYP3A4 inhibitor, but not a hepatic CYP3A4 inhibitor. Recent clinical studies now show that it is also a CYP2D6 and CYP2E1 inhibitor. Clinicians need to be aware of possible drug interactions involving this herbal.
Mol Nutr Food Res. 2008 Jan 23.Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK.
Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of approximately 30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (two extracts per study), each incorporating 16 healthy volunteers (eight females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum) and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre- and post- supplementation phenotypic trait measurements were determined for CYP2D6 using 8-h debrisoquine urinary recovery ratios (DURR).
Comparisons of pre- and post-supplementation DURR revealed significant inhibition ( approximately 50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb- drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.
Food Chem Toxicol. 2007 Dec;45(12):2359-65. Epub 2007 Jun 15. Effects of herbal products and their constituents on human Cytochrome P450(2E1) activity. Raner GM, Cornelious S, Moulick K, Wang Y, Mortenson A, Cech NB.
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 2.8 microM for hydrastine to 18 microM for berberine. The alkylamides present in E. purpurea and S. acmella also showed significant inhibition at concentrations as low as 25 microM, 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).