RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The bidirectional property of traditional Chinese medicines (TCMs) was recorded in the classic work Medicine Origin (Yi Xue Qi Yuan) as early as the Jin and Yuan dynasties of ancient China. Since then, this imperative theory has been applied to guide the clinical application of TCMs. Studies have been performed to investigate this phenomenon only over the last three decades. A limited number of reviews on the bidirectional role of TCMs have been published, and almost all current studies are published in the Chinese language. AIM OF THE REVIEW: The aim of this review is to provide the first comprehensive evidence regarding the bidirectional effects and the underlying mechanisms of TCMs and their active compounds. MATERIALS AND METHODS: Information relevant to opposing pharmacological activities or opposing properties exerted by TCM prescriptions, herbal medicines, and their active compound, as well as their mechanisms was summarized by searching Chinese and English databases, including the Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese Scientific Journal Database (VIP), Google Scholar, PubMed, Web of Science, Science Direct, and Wiley Online Library. RESULTS: Although the bidirectional regulation of TCMs has been applied in the clinic since ancient times in China, only limited reviews have been published in Chinese. The existing data showed that bidirectional effects can be found in TCM prescriptions, herbal medicines, and pure active compounds. Additionally, the bidirectional role of TCMs was primarily reported in the modulation of immune function, blood circulation and hemostasis, gastrointestinal motility, the central nervous system and blood pressure. This may because the therapeutic outcomes of these disorders are more obvious than those of other complicated diseases. Intriguingly, some herbal medicines have multiple bidirectional activities; for instance, Panax ginseng C. A. Meyer showed bidirectional regulation of immune function and the central nervous system; Astragalus membranaceus can bidirectionally regulate blood pressure and immune function; and Rheum officinale Baill exerts bidirectional effects on blood circulation and hemostasis, gastrointestinal motility and immune function. The mechanisms underlying the bidirectional effects of TCMs are largely attributed to the complexity of herbal constituents, dosage differences, the processing of herbal medicine, and compatibility of medicines, the physiological conditions of patients and adaptogenic effects. CONCLUSION: Uncovering the bidirectional effects and mechanisms of TCMs is of great importance for both scientific research and clinical applications. This review may help to facilitate the recognition of the bidirectional role of TCMs, to explain some seemingly-opposite phenomena in the pharmacological study of herbal medicines and to provide guidance for TCM practitioners.