Gut microbiota-mediated metabolism of Panax notoginseng saponins and its role in pharmacokinetics and pharmacodynamics

Panax notoginseng saponins (PNS) are a class of effective ingredients in Notoginseng Radix et Rhizoma, a well-known herbal medicine called San-Qi in Chinese. After oral administration, PNS inevitably interacts with gut microbiota, and thus affect the pharmacokinetic profiles and pharmacological effects. To date, studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically. Herein, we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota, as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data. The metabolic pathways of primary saponins are proposed, and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota. Specific microorganisms and enzymes involved in the metabolic processes were summarized. Gut microbiota is deeply involved in the metabolism of PNS, affects the pharmacokinetic profiles, and produces a series of active metabolites. These metabolites were documented to play an essential role in the efficacy of the parent compounds. Future studies should focus on strengthening the real-world evidence, defining the interaction between gut microbiota and PNS, and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS. These information would be useful for further research and clinical application of PNS.