Sweroside: A comprehensive review of its biosynthesis, pharmacokinetics, pharmacology, and safety

Sweroside is a naturally occurring iridoid compound known for its various biological activities. Despite growing interest, the fragmented nature of existing research and the lack of a comprehensive review have hindered a clear understanding of its therapeutic potential and research gaps. This review aims to provide an integrated overview of the research progress on sweroside, thereby highlighting current progress and proposing directions for future research. In the biosynthetic pathway of sweroside, the upstream formation of iridotrial is better characterized than its downstream structural modification steps. Following oral administration, sweroside exhibits moderate absorption, extensive tissue distribution, and diverse metabolites primarily formed through parental modifications, aglycone metabolism, and N-heterocyclization of the aglycone. To date, no serious side effects have been reported for sweroside. However, substantial gaps remain in the relevant research. Preclinical studies have indicated that sweroside has the potential to ameliorate metabolic dysfunction-associated steatotic liver disease (MASLD) and has cardioprotective, antiosteoporosis, and antitumor activity. These activities are linked to its ability to regulate energy and metabolic homeostasis, as well as to mediate anti-inflammatory and antioxidant responses. The clinical potential of sweroside may be limited by its poor bioavailability. Key priorities for sweroside include the identification of anti-MASLD active metabolites and mechanisms, standardized preclinical toxicological assessments, optimization of its pharmacokinetic properties and targeting efficiency, and functional characterization of key enzymes involved in its downstream biosynthesis.