Lithocarpus litseifolius leaf extract and its flavonoids alleviate hyperuricemia via TLR2/PI3K/NF-κ B pathway inhibition and gut microbiota modulation

Abstract

Lithocarpus litseifolius (Hance) Chun (Lithocarpus polystachyus rehd.) is a medicinal and edible plant. This study investigated the therapeutic effects of Lithocarpus litseifolius (LLL) leaf extract and its five key flavonoids on hyperuricemia (HUA) in a rat model. HUA was induced by potassium oxonate and adenine, followed by a 14-day treatment with LLL extract, its flavonoids (isoquercitrin, phlorizin, trilobatin, quercetin, phloretin), or benzbromarone. The results demonstrated that LLL extract and its flavonoids, particularly phlorizin and trilobatin, significantly (P < 0.05) reduced serum uric acid and BUN levels, ameliorated renal dysfunction, and attenuated hepatic xanthine oxidase activity and inflammation. Network pharmacology and molecular docking identified TNF as a key target, and experiments confirmed the modulation of the TLR2/PI3K/NF-κ B signaling pathway. Furthermore, 16S rRNA sequencing revealed that the treatments altered the gut microbiota composition in HUA rats. These findings indicate that LLL and its flavonoids alleviate HUA through multi-target mechanisms, providing a scientific basis for their development as functional products against HUA.