Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou 221004, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou 221004, China.
Phytomedicine. 2019 May;58:152866. doi: 10.1016/j.phymed.2019.152866. Epub 2019 Feb 19.
Herbal compatibility of compound formulas can enhance therapeutic effects or reduce side effects of the monarch drugs, but majority of compatibility mechanisms are still unknown. Sangju-Yin, a well-known Chinese compound formula, is currently used to treat common cold in clinical.
In this study, we proposed a strategy to explore the compatibility mechanism of Sangju-Yin by investigating P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs.
Under the guidance of traditional Chinese medicine theory, the constituent herbs of Sangju-Yin were divided into four groups, including monarch drugs, monarch drugs with addition of minister drugs, monarch drugs with addition of minister and adjuvant drugs, as well as the whole recipe, namely monarch drugs with addition of minister, adjuvant and conductant drugs. Their effects on rats in vivo P450 (CYP1A2, CYP2A3, CYP2C6, CYP2C11 and CYP3A1) activities after oral administration were evaluated using probe drug assay based on LC-MS/MS. Moreover, effects of the four groups of herbs on mRNA expression of P450 enzymes after oral administration, as well as in vitro P450 activities after co-incubation, were investigated to explore the underlying mechanisms.
Comparing with monarch drugs, addition of different constituent herbs significantly enhanced CYP1A2 and CYP2C6 activities, and inhibited CYP2A3 and CYP3A1 activities, indicating their possible influences on plasma concentrations of active constituents in the monarch drugs. Mechanism study suggested that these herbs affected P450 activities by transcriptional regulation and/or direct interaction with the enzymes.
This study clarified the compatibility mechanism of Sangju-Yin from the aspect of P450 enzymes-based metabolic interactions, which would benefit better understanding of the therapeutic basis of Sangju-Yin.
复方制剂的草药配伍可以增强君药的疗效或降低其副作用，但大多数配伍机制仍不清楚。桑菊饮是一种著名的中药复方制剂，目前临床上用于治疗感冒。
本研究拟通过考察君药与其他组成草药之间基于 P450 酶的代谢相互作用，探讨桑菊饮的配伍机制。
根据中医理论，将桑菊饮的组成草药分为四组，包括君药、君药加臣药、君药加佐使药以及全方，即君药加臣、佐、使药。采用基于 LC-MS/MS 的探针药物法，考察各组药物口服给药后对大鼠体内 P450（CYP1A2、CYP2A3、CYP2C6、CYP2C11 和 CYP3A1）活性的影响。此外，还考察了各组草药口服给药后对 P450 酶 mRNA 表达的影响，以及共孵育后对 P450 酶活性的影响，以探讨其潜在机制。
与君药相比，加入不同的草药成分显著增强了 CYP1A2 和 CYP2C6 的活性，抑制了 CYP2A3 和 CYP3A1 的活性，表明它们可能影响君药中活性成分的血浆浓度。机制研究表明，这些草药通过转录调控和/或与酶的直接相互作用影响 P450 活性。
本研究从 P450 酶代谢相互作用的角度阐明了桑菊饮的配伍机制，有助于更好地理解桑菊饮的治疗基础。
