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Nowadays, whereas herbal supplements are being increasingly popular worldwide, the incidence of herb-drug interactions are being reported spontaneously. One main mechanism causing herb-drug interactions is potential of an herb to modulate capacity or ability of drug-metabolizing enzymes, specifically cytochrome P450 (CYP450), a major superfamily of enzymes responsible for biotransformation in order to excrete xenobiotic out of the body. Herewith, cases of famous herbs, e.g., St. John’s wort, grapefruit, Ginkgo biloba, black pepper, and pomegranate, and their potentials in modulating CYP450 activities are being reviewed. St. John’s wort is a potent inducer of CYP3A4, CYP2E1, and CYP2C19 while, at the same time, being popularly used as a combination therapy in patients with depression. Grapefruit juice, extensively consumed due to its taste, nutritive value, and biological benefits, is a potent CYP3A4 inhibitor. G. biloba, one of the most consumed ethnomedicines especially in senior people and patients suffering from dementia, has been reported to inhibit CYP3A4. Black pepper, well known for its pungent taste and extensively used in numerous dishes, is a potent CYP3A4 inhibitor, and therefore, is known and used as a bioenhacer. Pomegranate, a fruit popularly consumed global due to its delicious taste and biological benefits, is reported to inhibit CYP3A4 similarly to grapefruit juice. Both practitioners and patients should be interested and concerned on information of herb-drug interaction, as ignorance can cause life-related consequences. Patients should acknowledge the impact of the self- co-administered therapies while practitioners should consider these supplements, either intentionally or unintentionally, which may convey potential effects on the therapeutic outcome or adverse toxicity.
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