Herb and Cytochrome P450 Enzyme Interactions

Planet Herbs Discussion Board: General Forum: Herb and Cytochrome P450 Enzyme Interactions
Top of pagePrevious messageNext messageBottom of page Link to this message  By Christina Mathis on Tuesday, May 06, 2008 - 09:37 pm:

The peppered vodkas and any bloody mary should demonstrate some of the theoretical effect we're talking about... hmm, I think maybe I feel some informal research coming on...

Top of pagePrevious messageNext messageBottom of page Link to this message  By Anne de Courtenay on Friday, April 18, 2008 - 08:07 am:

Interesting. I was making ginger syrup/lime/mint leaf white wine spritzers in Hawaii. Half of it is bubbly water so the effects were zero but I'll have to remember this factoid about SJW vs. ginger/pepper/etc. for the future! Same for chili-salt crusted margaritas.

Top of pagePrevious messageNext messageBottom of page Link to this message  By Michael Tierra on Thursday, April 17, 2008 - 11:22 pm:

Anne, so much of this is theoretical but the answer to your question is yes. On the reverse, don't sprinkle pepper or spices on your martini -- has anyone ever done that? .

Top of pagePrevious messageNext messageBottom of page Link to this message  By Anne de Courtenay on Thursday, April 17, 2008 - 08:46 pm:

OK, here's what may be a really naive question:

Suppose you're going to a wedding wherein there will probably be a fair amount of drinking (or whatever, insert scenario of your choice). If you want your liver to detoxify yourself of the effects of alcohol more quickly than usual, would taking St. John's Wort extract help you do so and ward off intoxication/ a hangover?

Top of pagePrevious messageNext messageBottom of page Link to this message  By Tracy Richardson on Thursday, April 17, 2008 - 04:33 pm:

Thanks for keeping us informed. I had herd of the liver enzymes and this gives me a clearer understanding of the way the work with different plants. Some people think they can't ever eat a grapefruit again if they are on certain drugs, it sound like it is just at the time of ingestion of the drugs that the two should not interact, for the enzyme shut down.

Appreciate the update.

Top of pagePrevious messageNext messageBottom of page Link to this message  By jim reinhart on Thursday, April 17, 2008 - 03:23 pm:

Another important medicinal that has also been shown to inhibit the cytochrome P450 enzyme system is Rx Salvia miltiorrhizae, dan shen. In a report by Qui f. and associates in Drug Metab Dispos. 2008 Apr 14, the authors investigated 7 active components in dan shen and found that they were potent to weak inhibitors of the enzyme system. This is very interesting in that it has been shown that dan shen is a very potent medicinal in microcirculation technology (capillary blood flow). Very good article about Salvia in ITM (Institute for Traditional Medicine). Salvia is a very important medicinal in the treatment of blood stasis especially with the elderly who have a tendency to be on multiple pharmaceuticals (polypharmacy)anyway.

Top of pagePrevious messageNext messageBottom of page Link to this message  By Kristyne Berg on Thursday, April 17, 2008 - 12:41 pm:

This is fascinating.

Top of pagePrevious messageNext messageBottom of page Link to this message  By Michael Tierra on Wednesday, April 16, 2008 - 10:40 am:

probably not many of you know about liver enzymes, especially the P450 group. These are how the liver detoxifies or neutralizes drugs, foreign or strange substances, etc. Drugs and strange tasting herbs are in the category of strange or unfamiliar and if liver enzymes are doing their job, they are busily trying to protect us from possible foreign or toxic substances. Pharmaceutical drug manufacturers know about this and will figure it into their method of creating drugs that will remain in the system long enough to do their intended job.

Keep in mind that most foods such as grapefruit or herbs only effect liver enzymes during one hour or so after ingestion. So if one takes grapefruit juice with certain drugs it inhibits P450 enzymes and will cause the drugs to be stronger, sometimes dangerously stronger, then intended. On the other hand taking St Johnswort with hyperforin intact, does a wonderful job of inducing liver P450 ad other enzymes to detoxify the effects of the drugs, thus rendering it less effective.

So the key words here are substances that inhibit (i.e. grapefruit juice) and substances that induce (i.e. St johnswort).

Obviously there is an opportunity that has not been fully explored to be able to alter the original dose of a drug taken with a substance that would inhibit its metabolism (breakdown) necessitating a lower dose of the drug. This has not been researched as yet to my knowledge.

Piperine in black pepper and in fact all spicy herbs inhibit P450 enzymes so taking a small amount of spice to antibiotics or in an herbal formula will make both more effective and longer lasting. This is why many formulas add a small amount of cayenne pepper, trikatu herbs such as black pepper, pippli or ginger. to a formula -- to increase utilization and absorption.

Its another wonderful case of science proving old time herbalism as sound and true.

Top of pagePrevious messageNext messageBottom of page Link to this message  By Michael Tierra on Wednesday, April 16, 2008 - 10:19 am:

Herb and Cytochrome P450 Enzyme Interactions

Yarnell E, Abascal K. Interaction of herbal constituents with cytochrome P450 enzymes. Altern Complement Ther. Oct 2007:239-247.
Cytochrome P450 (CYP450) enzymes are involved in the metabolism of many drugs and herbal medicines. This has led to recent concern over herb-drug interactions. Constituents of St. John's wort (SJW; Hypericum perforatum) induce CYP3A4, and constituents of grapefruit (Citrus decumana) inhibit it. The major CYP3A4-inducing constituent of SJW is hyperforin. SJW extracts with little or no hyperforin have little to no effect on CYP3A4 in humans. SJW has a broad effect on CYP450 enzymes and should not be administered with any drug that is metabolized by CYP3A4, such as estrogen analogue oral birth control pills, digoxin, warfarin, and cyclosporin. SJW's effect on CYP3A4 reduces the absorption of these drugs. The authors also write that the observed interactions do not always translate into changes in efficacy or toxicity, citing the example of SJW's interaction with quazepam, which does not affect the drug's pharmacodynamics. Furanocoumarins, fouranocoumarin polymers, and flavonoids from grapefruit are known inhibiters of CYP3A4. Grapefruit also inhibits the drug transporter p-glycoprotein. Grapefruit increases the absorption of drugs including immunosuppressives such as cyclosporin, statin drugs such as atorvastatin, and antiseizure drugs including carbamazepine. The authors write that grapefruit is not always contraindicated in patients taking CYP3A4-metabolized drugs if there is close supervision by an experienced clinician. However, the use of grapefruit as a dose-sparing agent needs more research, and it is particularly risky with drugs with a narrow therapeutic index. Grapefruit and other bitter citrus fruits have also been shown to improve the absorption of substrates of CYP2A6 by blocking the effect of the enzyme. An example is the effect on nicotine, which may make grapefruit a useful dose-sparing agent for nicotine substitution.

Several members of the Boraginaceae and Asteraceae families, such as comfrey (Symphytum officinale), contain unsaturated pyrrolizidine alkaloids (PAs) that are converted by CYP3A enzymes into toxic intermediates. This may explain the variation in the toxicity of PAs because the activity of these enzymes varies between individuals. CYP3A4 inhibitors like grapefruit may theoretically reduce the toxicity of PAs, but research is needed to confirm this. Alkylbenzenes, such as safrole from Sassafras spp. and betel nut (Areca catechu), are also converted to toxic intermediates, including the carcinogenic 1'-hydroxysafrole, by CYP450 enzymes. Research suggests that individuals with low levels of CYP2A6 may have resistance to the toxicity of betel nut. The authors write that more research on the role of CYP3A4 enzymes in plant toxicities is warranted.

Piperine, an alkaloid found in black pepper (Piper nigrum), is an inhibitor of CYP3A4 and may affect other CYP450 enzymes. Piperine increases the absorption of phenytoin, propanolol, and theophylline, and it may have potential as a dose-sparing agent. Piperine has been shown to significantly enhance the absorption of curcumin, an antioxidant constituent of turmeric (Curcuma longa) that also inhibits several CYP450 enzymes in vitro. The authors write that more research is needed to determine if turmeric and/or curcumin could cause drug-herb interactions. Cruciferous vegetables like broccoli (Brassica oleracea italica) and watercress (Nasturtium officinale) contain isothiocyanates, which inhibit CYP2E1 and stimulate CYP1A1 and CYP1A2. Although the mechanism for the anticarcinogenic effects of cruciferous vegetables is very complex, it involves their ability to accelerate the breakdown of carcinogens by CYP1A1 and CYP1A2. Eating broccoli together with charred meats containing carcinogenic heterocyclic amines may reduce the damage caused by these compounds; however, more research is needed to confirm this. Isothiocyanates, particularly indole-3-carbinol, induce CYP1A2 and may reduce the risk of metabolizing estrogen into harmful metabolites with minimal adverse side effects. Sweet Annie (Artemisia annua) is the source of the antimalarial compound artemisinin, which is metabolized by CYP2B6, CYP2A6, and CYP3A4. As well as being metabolized by CYP2B6, artemisinin also induces this enzyme, which leads to decreased absorption of artemisinin doses over a period of several days, so artemisinin is prescribed for 5-7 days at a time and is combined with other antimalarials. Resveratrol is an antioxidant constituent found in red wine. CYP450 enzymes are involved in the hydroxylation of resveratrol to the metabolite piceatannol, which may have more potent cardioprotective and antineoplastic effects and/or synergistic effects. This is a probable example of the transformation of medicinal plant constituents into more active substances by CYP450 enzymes. CYP2C19 is an enzyme that affects the disposition of a small number of drugs. Ginkgo (Ginkgo biloba) and artemisinin may induce CYP2C19, decreasing serum levels of the drug omeprazole.

Most research has focused on the ways in which herbal medicines may interfere with drugs metabolized through the CYP450 pathway. However, research is also needed concerning the ways in which drugs may interfere with the beneficial effects of herbal medicines. Potential interactions between herbal constituents through CYP450 enzymes, as well as the mechanisms through which CYP450 enzymes may increase the beneficial effects of herbal constituents or change them into toxic metabolites also need exploration. Genotypic and phenotypic differences among individuals that affect CYP450 enzymes may also affect the actions of herbal medicines. The authors conclude that there is clearly a need for more research and understanding "of the relationships between botanical products and the CYP450 system."

-Marissa N. Oppel, MS