Flavonoid rich extract of Trigonella foenum-graecum leaves ameliorate liver fibrosis

Liver fibrosis is a leading cause of mortality and morbidity globally. For decades, plant secondary metabolites such as flavonoids and saponins have attained much consideration due to their safer therapeutic potential against chronic liver diseases. Trigonella foenum-graecum (Common name “Fenugreek”) is an annual herb used as a spice to increase the taste and aroma of food. Its fresh leaves are used as food and are rich in flavonoids. In the current study antifibrotic potential of Trigonella foenum-graecum flavonoid-rich leaf extract (TF) was evaluated in CCl 4 -induced hepatic fibrosis in mice. The ALT, AST, MDA, CAT, and GSH analysis illustrated that the treatment group significantly reverses CCl 4 -induced liver damage. The TF extract was found to be rich in quercetin and kaempferol derivatives analyzed through ESI-MS/MS. After four weeks of the TF treatment, hepatocyte architecture improved and collagen deposition in mice liver tissues reduced considerably. The expression of fibrotic markers, including COL-IA, α-SMA, PDGF, and TIMP1, was downregulated, and MMP3 was upregulated significantly at mRNA and protein levels. Interestingly, TF significantly downregulated NF-κB expression and TGF-β/Smad signaling pathway and upregulated miR-146a and miR-29b. Taking together, these results demonstrated that Trigonella foenum-graecum flavonoid-rich leaf extract ameliorated liver inflammatory and fibrogenic responses through miR-146a/miR-29b/TGF-β/Smad axis.