Herb-drug interactions involving pueraria lobata and its bioactive constituents: A comprehensive review

Abstract

INTRODUCTION

Pueraria lobata (PL) is a traditional Chinese medicinal herb that is rich in isoflavonoids, such as puerarin and daidzein. It is widely used to treat cardiovascular, metabolic and oncological disorders. As PL is increasingly being co-administered with conventional drugs, herb–drug interactions (HDI) have emerged as a significant clinical concern. A comprehensive synthesis of the current evidence base is required to clarify the pharmacodynamic and pharmacokinetic profiles of PL-related interactions, as well as their implications for clinical practice.

METHODS

We conducted a comprehensive review of experimental and clinical studies on HDI involving PL and its bioactive constituents. Literature was retrieved from PubMed, CNKI, and Google Scholar up to April 2024. Studies were included if they reported on the pharmacodynamic or pharmacokinetic interactions between PL (or its constituents) and therapeutic drugs. Twenty-three studies met the eligibility criteria: Twelve addressed pharmacodynamic interactions and eleven addressed pharmacokinetic interactions.

RESULTS

In terms of pharmacodynamics, PL exhibited both synergistic and antagonistic effects. Synergistic outcomes included enhanced efficacy in terms of cardiovascular protection, osteoporosis prevention, glycaemic control and chemosensitisation in cancer therapy. Conversely, adverse outcomes were observed, including attenuation of the antiplatelet effect when combined with warfarin or dual antiplatelet therapy and increased mortality when combined with methotrexate in animal models. In terms of pharmacokinetics, puerarin and other constituents were found to modulate cytochrome P450 enzymes and transporters. The effects included inhibiting CYP2D6, suppressing CYP3A, inducing CYP1A2 and altering P-glycoprotein activity. These mechanisms contribute to variable drug metabolism and bioavailability across co-administered agents.

DISCUSSION

Evidence suggests that PL can have beneficial or harmful effects on HDI, depending on the therapeutic context. However, the available data is limited and is largely derived from preclinical models. There is a lack of rigorous clinical trials and the roles of minor constituents remain under-explored. Research gaps include a lack of data on high-risk populations and an incomplete understanding of the mechanisms of pharmacodynamic interactions. To ensure the rational and safe integration of PL into modern medical practice, future work should prioritise translational studies and broaden the focus beyond puerarin to establish safety profiles.