Abstract
Chestnut shell flavonoid (CSF) has been proved to exhibit pancreatic lipase inhibitory effect by our previous research. To further study the effect of CSF on lipid metabolism, three related targets, including pancreatic lipase, L-02 cells and gut microbiota, were investigated. Firstly, the flavonoid compounds in CSF were identified by ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI–MS/MS). Three key flavonoids—epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) were also found to have significant pancreatic lipase inhibition. Molecular docking illustrated that these flavonoids could bind to pancreatic lipase via hydrogen bonds. Additionally, CSF dose-dependently inhibited lipid accumulation in steatotic hepatic L-02 cells, reducing triglycerides (TG), total cholesterol (TC), and non-esterified fatty acids (NEFA). Gut microbiota analysis showed that CSF modulated microbial composition, lowering the Firmicutes/Bacteroidetes ratio, suggesting potential lipid metabolic regulatory effect. In conclusion, flavonoids in CSF could inhibit pancreatic lipase, regulate hepatocyte metabolism and gut microbiota to achieve multi-target regulation of lipid metabolism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-026-02126-8.