St, John’s Wort and CYP450 Pathways

Dürr et al. (2000) gave 300 mg of St. John’s Wort to healthy volunteers three times a day for two weeks.  They found that this induced CYP3A4 in both the liver and the intestines, which explained the interactions that had been observed between St. John’s wort and certain drugs.  It seems that it reduced the effect of the drugs on two levels- first it decreased the amount of the drug that was absorbed, and then it speeded up the rate at which the liver processed it.  CYP3A4 is the same enzyme that is inhibited by grapefruit juice (Ho et al., 2000), so I would caution anyone whose prescriptions say not to drink grapefruit juice that they should probably avoid St. John’s wort as well.  This could be the case for half of all prescriptions (Gurley et al., 2005), so should be investigated whenever anyone is on any prescriptions. 

 

St. John’s wort was also found to induce CYP2E1 by Gurley et al. (2005), who note older people as a population that might be taking prescriptions that would be affected by a change in the activity of this enzyme, and that their age might also inhibit the enzyme, leading to a potential magnification of the interaction with herbs that inhibit CYP450 enzymes.  However, in this case, the herb was an inducer, and they found that the interaction was less pronounced than what had been found in another study with younger people. 

 

Dutkiewicz et al. (2001) report on an indirect way that exposure to St. John’s wort could possibly affect CYP450 enzymes.  They found high levels of bacterial endotoxins in the air where workers were processing St. John’s wort herb on a commercial scale.  These endotoxins could in turn inhibit CYP450 enzymes (Shedlofsky et al., 1997).

 

References:

 

Dürr, D., Stieger, B., Kullak-Ublick, G. A., Rentsch, K. M., Steinert, H. C., Meier, P. J., & Fattinger, K. (2000). St John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4*. Clinical Pharmacology & Therapeutics, 68(6), 598–604. 

 

Dutkiewicz, J., Krysińska-Traczyk, E., Skórska, C., Sitkowska, J., Prazmo, Z., & Golec, M. (2001). Exposure to airborne microorganisms and endotoxin in herb processing plants. Annals of Agricultural and Environmental Medicine : AAEM, 8(2), 201–211. 

 

Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Cui, Y., & Ang, C. Y. W. (2005). Clinical Assessment of Effects of Botanical Supplementation on Cytochrome P450 Phenotypes in the Elderly: St John’s Wort, Garlic Oil, Panax ginseng and Ginkgo biloba. Drugs & Aging, 22(6), 525–539. 

 

Ho, P. C., Saville, D. J., Coville, P. F., & Wanwimolruk, S. (2000). Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products. Pharmaceutica Acta Helvetiae, 74(4), 379–385. 

 

Shedlofsky, S. I., Israel, B. C., Tosheva, R., & Blouin, R. A. (1997). Endotoxin depresses hepatic cytochrome P450-mediated drug metabolism in women. British Journal of Clinical Pharmacology, 43(6), 627–632.