Saponins From Chenopodium Quinoa Willd. Improve Insulin Resistance and Restore Pancreatic β‐Cell Function via Anti‐Endoplasmic Reticulum Stress Mechanisms

ABSTRACT This study investigated the effects of pentacyclic triterpene saponins from Chenopodium quinoa Willd. on insulin resistance (IR). Six saponin monomers (C1–C6) were isolated using semi‐preparative liquid chromatography. In the T2DM zebrafish model, these compounds reduced the level of glucose, TC, TG, LDL‐C, ALT, and AST, while increasing the level of HDL‐C. They exerted antioxidant effects by enhancing GSH and SOD activities and reducing MDA levels. Histological analysis revealed restored liver morphology and reduced liver injury. Among the six compounds, C1, C4, and C5 demonstrated particularly strong efficacy in ameliorating IR by activating the insulin signaling pathway and suppression of ERS‐related proteins (ATF6, IRE1, PERK, GRP78, and CHOP), while also inhibiting inflammation and apoptosis. Using a transgenic Tg(ins: GFP) zebrafish model, we showed that C1, C4, and C5 protected pancreatic β‐cells by reducing ERS‐mediated apoptosis and restoring cellular function. These findings highlight the therapeutic potential of quinoa saponins for managing T2DM and its complications.