The modern scientific interpretation of ancient wisdom: a review of the phytochemistry and pharmacology of Erzhi Pill and its constituent botanical drugs

Erzhi Pill has been used in traditional Chinese medicine for nearly six centuries. It concurrently delivers nourishing Liver-Kidney Yin (lower) and clears floating deficiency fire (upper) to holistically tackle both the root cause and symptoms of disorders including osteoporosis and menopausal syndrome. Thus, Erzhi Pill has an established reputation as the primary formula for "clearing the upper and tonifying the lower." While modern clinical and experimental evidence has demonstrated the therapeutic potential of Erzhi Pill, its further development is impeded by several challenges, including simplistic quality control markers, unclear pharmacological mechanisms, and imprecise clinical indications. To support the quality standardization and enhanced clinical use of Erzhi Pill, this review systematically evaluates its constituent botanical drugs and final formula across multiple domains, including the resource distribution of its metabolite constituent botanical drugs, phytochemical profiles, efficacy, mechanisms, and applications, thereby establishing a foundation for further development of Erzhi Pill. Furthermore, we summarized future research directions of Erzhi Pill, which may include exploring integrated quality control markers and pharmacodynamic substances, adopting synchronized screening strategies for active ingredients and targets to elucidate the target network, and clarifying indications and precise medication strategies through evidence-based medical methodologies.