The scientific basis of synergy in traditional Chinese medicine: physicochemical, pharmacokinetic, and pharmacodynamic perspectives

Traditional Chinese medicine, with millennia of history, demonstrates significant therapeutic efficacy against diverse diseases. A key characteristic of traditional Chinese medicine lies in the use of compound formulas-multi-herb concoctions that enhance efficacy and mitigate toxicity. The synergy within these formulas arises fundamentally from interactions among multiple active components. Recently, growing experimental studies have aimed to elucidate the scientific principles underlying synergy in traditional Chinese medicine. By reviewing literature over the past 30 years, this review summarizes that traditional Chinese medicine synergy manifests primarily through three key mechanisms: physicochemical interactions, pharmacokinetic processes, and pharmacodynamic effects. Furthermore, it provides an overview of methodological advances for studying these mechanisms, including HPLC fingerprinting, network pharmacology, and metabolomics, among others. Finally, it highlights current research limitations as well as challenges in traditional Chinese medicine modernization. This review systematically synthesizes current knowledge on traditional Chinese medicine synergy to establish a foundation for compatibility research and promote evidence-based clinical application.