Nonalcoholic steatohepatitis (NASH) is characterized by liver steatosis, inflammation and metabolic disorders, and current treatment options are limited. The total flavonoids extracted from the pueraria flower (TFP) have been reported to have antioxidant and hepatoprotective effects. However, the effects of TFP on NASH and its underlying mechanisms remain unclear. To gain more insight into the pharmaceutical value of TFP for treating NASH, the chemical composition of TFP was analyzed by UPLC‒ESI‒MS/MS. A NASH mouse model was established to evaluate the effects of TFP on liver and fat indices, serum biochemical parameters, and liver histopathology. The composition of the gut microbiota was analyzed by 16S rRNA sequencing, and the metabolome of the liver was studied. Thirty-five flavonoids were identified as the main components. In NASH mice, TFP was able to reduce liver and epididymal fat indices and decrease serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase levels. Histological analysis confirmed the reduction in lipid deposition and improvement in liver structure. Additionally, TFP helped restore microbial diversity, increase the abundance of beneficial bacteria, and correct the metabolic functions related to the gut microbiota. Metabolomic analysis indicated that TFP could reverse the bile acid, fatty acid, and amino acid metabolic disorders caused by NASH, reduce the levels of harmful metabolites, and restore the levels of beneficial metabolites. Collectively, our data reveal that TFP intervention correlates with comprehensive amelioration of NASH-associated pathological phenotypes, accompanied by restored intestinal microecology, corrected hepatic metabolic disorders, and balanced lipid signaling protein expression. While these multi-omic and biochemical observations establish correlative links between TFP treatment and improved liver function, definitive causal molecular cascades need further functional experimental verification along the gut-liver axis.

To Cite This Article: Luo Y, Han Y, Zhang Y, Chen B, Zhao Q, Bi W, Sui J, Duan H, Zou F, Xiao X and Wu Y, 2026. Treatment and mechanism of total flavonoids from pueraria flower on nonalcoholic steatohepatitis (NASH) mice. Pak Vet J, 46(7): 1708-1721. http://dx.doi.org/10.29261/pakvetj/2026.164