Metabolic profiling of Solanum villosum Mill subsp. miniatum (bernh. ex willd.): Hepatoprotective and antifibrotic activity in a rat model of liver fibrosis

Abstract

Aim/Background: To assess the liver antifibrotic action of ethanolic extract of aerial parts of Solanum villosum Mill subsp. miniatum (Bernh. ex Willd.) (SVE) and correlate this activity with its high performance liquid chromatography-quadrupole time of flight (HPLC-qTOF) Electrospray Ionisation Mass Spectrometry (ESIMS) phytochemical profile. Materials and Methods: The median lethal dose of SVE was determined, and a rat model of carbon tetrachloride (CCl4)-induced liver fibrosis was used to evaluate its antifibrotic activity. Markers for hepatotoxicity, fibrosis, and oxidative stress were assessed, and histopathological features of liver tissues were examined. Metabolite profiling of SVE was achieved via HPLC-qTOF-ESIMS coupled with Photodiode array (PDA). Liver fibrosis was induced in rats by oral administration of CCl4for 6 weeks. Silymarin (positive control) and SVE (100 and 250 mg/kg) were orally administered daily for 6 weeks. Results: Compared to CCl4-intoxicated group, administration of SVE obviously ameliorated fibrosis of the hepatic capsule associated with aggregation of multiple focal fat cells formation. Both silymarin and SVE ameliorated the rise in serum markers of hepatotoxicity (alanine transaminase, aspartate transaminase, and alkaline phosphatase), markedly attenuated CCl4-induced oxidative stress. The antifibrotic activity of SVE was evidenced by inhibiting the rise in hepatic hydroxyproline content and accumulation of collagen. This was confirmed by the ability of SVE to inhibit alterations in expression of the fibrosis-related genes Collagen Iα, matrixmetalloproteinase-2 (MMP-2), tissue inhibitor matrix metalloproteinase-2, and transforming growth factor beta 1. HPLC-qTOF-ESIMS analysis of SVE revealed the presence of 47 metabolites, among which 33 were tentatively identified. Conclusion: SVE exhibited hepatoprotective and antifibrotic activities in rats by enhancing the antioxidant capacity and regulating expression of fibrogenic mediators.