Metabolism-involved drug interactions with traditional Chinese medicines in cardiovascular diseases

Herbal medicines have been widely used for the past millennia. Traditional Chinese medicine (TCM) is a major modality in Chinese medical care and has garnered global attention owing to its pharmacological effects and multi-targeted actions. The increased incidence of sequential or concurrent use of herbs and drugs in patients forces us to consider herb-drug interactions (HDIs) in this modern era. One of the main causes of HDIs is modulation of drug metabolism, in which cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and transporters play primary roles. In this review, we focus on in vivo studies of HDIs, particularly in the treatment of cardiovascular disease (CVD), which is currently the leading cause of disease-related mortality worldwide. A total of 55 HDIs are summarized, and their potential underlying mechanisms are examined. The pharmacokinetic (PK) and pharmacodynamic (PD) effects of three single herbs (Danshen, Ginseng, and Ginkgo) and four compound prescriptions (Shenmai injection, Shengmai-San, Shu-Jing-Hwo-Shiee-Tang, and Wu-Chu-Yu-Tang) are discussed. Due to the complex compositions and PK/PD profiles of TCMs, the determinants of significant HDIs have been listed to further define the pros and cons of HDIs in medical care.