Lithocarpus litseifolius leaf extract and its flavonoids alleviate hyperuricemia via TLR2/PI3K/NF-κB 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 leaf (LLL) 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 reduced serum uric acid and blood urea nitrogen 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-κB 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.