Traditional Chinese medicine (TCM) formulas with fixed combinations rely on "sovereign, minister, assistant and guide" and
fuzzy mathematical quantitative law, leading to greater challenges for the identification of active ingredients. Transformation and metabolic
studies involving the Phase I drug-metabolizing enzyme cytochrome P450 (CYP) might potentially solve some of these challenges.
The pharmacological effects can not be attributed to one active ingredient in TCMs, but integrated effects resulting from the combined
actions of multiple ingredients. However, it is only after long-term administration that most ingredients exert their actions, which can result
in prolonged exposure to herbs in vivo. Therefore, interactions between herbal compounds and CYPs appear to be inevitable. Yet unlike
Western drugs, experimental determination of the absorption and disposition properties is not commonly carried out for TCMs.
Moreover, the use of TCM as injections is an innovation aimed to improve efficiency in extensive clinical use in Mainland China. Therefore,
in recent years, cases of adverse drug reactions (ADR) mainly concerning allergic reactions involving TCMs such as ShenMai injection
and QingKaiLing injection have been reported, which have attracted attention with regard to the legal responsibilities for TCM approval.
The lack of information on the ADME characteristics, especially the metabolic stability and interaction potential between CYPs
and herbs, increases ADR occurrence due to TCMs. In this article, we review the most common herbs used in TCM prescriptions and
fixed combinations of their usable frequency, and summarize the current understanding of the ability of phytochemical ingredients to act
as substrates, inhibitors or inducers of human CYP enzymes, through which the key role of CYP enzymes on the herb disposition and
toxicity is highlighted. The potential interaction between herbal phytochemicals and CYP enzymes dominates the target exposure, which
further helps to elucidate the herbal pharmacological basis, assess the individual toxic risk of herbal remedies and gain mechanistic insight
into herb–drug interactions (HDIs).
Keywords: Phytochemicals, TCM, cytochrome P450, efficacy, toxicity, Traditional Chinese Medicines, Human Cytochrome P450 Enzymes, pharmacological effects, Western drugs, QingKaiLing injection, CYPs, adverse drug reactions
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