Chemical Constituents of Piper sintenense Hatusima with Antigouty Arthritis Activity: From Discovery to Mechanistic Study

Abstract Piper sintenense Hatusima, a plant traditionally used in China for both medicinal and dietary purposes, remains largely unexplored regarding its phytochemical composition, particularly its high-polarity fraction. This study aims to investigate the phytochemical constituents and antigouty arthritis (GA) potential of the high-polarity fraction of P. sintenense. Anti-GA activity-guided phytochemical isolation combined with UPLC-Orbitrap-MS analysis enabled the isolation of 32 compounds from the n-BuOH fraction (NF) of P. sintenense, including 11 novel compounds (1–11) and 21 known ones (12–32). Among the isolates, compound 26, although a known compound, exhibited significant anti-GA activity both invitro and invivo, with no observable toxicity in acute toxicity assays. Integrative proteomics and mechanistic studies revealed that compound 26 exerts its effects by markedly suppressing oxidative stress. These findings offer novel insights into P. sintenense and highlight its potential as a medicinal and edible plant for managing GA.