Saint John’s Wort

Saint John's Wort (Hypericum perforatum) is an herb commonly used as an antidepressant. How it works to combat depression is currently unknown. It has been shown to increase serotonin levels. Saint John's Wort is an extremely weak MAO inhibitor, too weak to have any effect at normal doses. There is debate to whether or not Saint John's Wort acts as a serotonin reupdate inhibitor.

Oral administration of Saint John's Wort for 14 days in healthy volunteers resulted in a 1.4-fold increase in P-gp expression.[1]

Saint John’s Wort extract is a potent inhibitor of SULT1A3 in vitro with an IC50=98.0 μg/ml[4].

Cytochrome P450 Enzyme Interactions

Saint John’s Wort has been shown to dramatically interact with several medications and herbs. It affects several cytochrome P450 enzymes responsible for drug metabolism. CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 are all affected.

Enzyme Interaction At High Doses Verified In Humans
CYP1A2 Potent Inhibition ?
CYP2C9 Potent Inhibition ?
CYP2C19 Potent Inhibition [2] ?
CYP2D6 Potent Inhibition ?
CYP2E1 100% Inhibition [2] ?
CYP3A4 Weak Inhibition [3] ?
Enzyme Interaction At Low Doses Verified In Humans
CYP1A2 No effect [3] ?
CYP2B6 Induction [1] Yes
CYP2C9 Potent Induction [3][1] Yes
CYP2C19 Potent Induction [2] Yes
CYP2D6 Mild Induction (No effect from hyperforin [3]) ?
CYP2E1 Potent Induction [2] Yes
CYP3A4 Potent Induction [3][1] Yes

One human liver hepatocyte in vitro study showed a 65% induction for CYP2E1, using low doses only. Inhibition was evident at high doses. In another study a daily intake of 900 mg St John’s wort for 28 days in humans showed an induction of CYP2E1 activity by increasing the 6-hydroxychlorzoxazone/chlorzoxazone serum ratio by nearly 30%.[2]

1. Shu-Feng Zhou, Zhi-Wei Zhou, Chun-Guang Li, Xiao Chen, Xiyong Yu, Charlie
Changli Xue, and Adrian Herington Identification of drugs that interact with herbs in drug development; Drug Discovery Today 12(15-16):pp. 664-673; Adrian (2007) (Download Attached PDF Document)
2. Basic Clin Pharmacol Toxicol. 2009 Jul;105(1):58-63. doi: 10.1111/j.1742-7843.2009.00412.x. Epub 2009 Apr 3;
Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes; Hellum BH, Hu Z, Nilsen OG; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; PubMed PMID: 19371257 (Download Attached PDF Document)
3. Komoroski BJ, Zhang S, Cai H, Hutzler JM, Frye R, Tracy TS, Strom SC, Lehmann T, Ang CY, Cui YY, Venkataramanan R;
Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures; Drug Metab Dispos. 2004 May;32(5):512-8; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; PubMed PMID: 15100173
4. Inhibitory effects of herbal extracts on the activity of human sulfotransferase isoform sulfotransferase 1A3 (SULT1A3).
Nagai M, Fukamachi T, Tsujimoto M, Ogura K, Hiratsuka A, Ohtani H, Hori S, Sawada Y. PubMed PMID: 19122289
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