Paris Saponins: A Comprehensive Review of Their Chemical Composition, Pharmacological Effects, and Mechanisms of Action.

Paris polyphylla is a traditional medicinal plant widely used in Chinese and Indian medicine, and its steroidal saponins are regarded as the principal bioactive constituents responsible for many of its therapeutic effects. This review aims to provide an integrated overview of the chemical composition, nomenclature, pharmacological activities, molecular mechanisms, in vivo evidence, translational prospects, and safety of Paris saponins. Published evidence was narratively synthesized according to saponin structural features and sugar-chain composition, with particular attention to major monomers including Polyphyllin I, II, III, V, VI, VII, H, C, and G and to the standardization of their nomenclature. Evidence from cell-based, animal, and mechanistic studies was further organized to link individual saponins with their reported biological effects and molecular targets. Current evidence indicates that Paris saponins exhibit broad biological activities, including antitumor, antimicrobial, antiviral, anti-inflammatory, analgesic, hemostatic, immunomodulatory, organprotective, anthelmintic, and antioxidant effects. Mechanistically, these compounds regulate multiple molecular processes, including apoptosis, autophagy, cell-cycle progression, oxidative homeostasis, inflammatory signaling, immune responses, and tumor invasion and metastasis, through pathways such as PI3K/AKT/mTOR, MAPK, NF-κB, and related signaling networks. Their pharmacological effects are strongly influenced by structural differences in steroidal aglycones, sugarchain composition, and glycosidic linkages. Although accumulating in vivo studies support their therapeutic potential, clinical translation remains constrained by hemolytic toxicity, limited bioavailability, complex metabolism, variable exposure-response relationships, and insufficient clinical evidence for structurally defined monomers. Overall, Paris saponins represent promising multitarget natural products, but future studies should integrate pharmacokinetics, toxicology, standardized nomenclature, structure-activity relationships, and well-designed clinical investigations to facilitate their safe and rational development.