Cucurbita pepo is widely utilized as a vegetable and is reported to possess hepatoprotective activity. However, its hepatoprotective molecular mechanisms are not yet elucidated. The current study utilized multiple in silico approaches to identify the mechanisms of active biomolecules of C. pepo. Additionally, the C. pepo effect on Isoniazid (INH) induced liver cirrhosis was evaluated in experimental animals. First, in silico studies, viz., genes pathways and network analysis, hub gene molecular docking and dynamics were employed. Secondly, C. pepo steroid fraction was subjected to liquid chromatography-mass spectrometry analysis and thirdly, hepatoprotective activity of both hydroalcoholic extract and steroid fraction was evaluated in INH-induced liver cirrhosis in rats. Out of 135 compounds, 18 (mainly phytosteroids) were identified to modulate 4 main pathways in liver disease. Among the predicted targets, NRIH3 and 3-hydroxy-3-methylglutaryl-CoA reductase were identified as a hub genes. Schottenol and Alpha-Spinasterol formed stable contacts with NRIH3 throughout 30 ns molecular dynamics simulation. INH (50 mg/kg/day) treatment elevated aspartate aminotransferase, alanine transaminase, alkaline phosphatase, serum bilirubin, total bilirubin, total protein, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, very low density lipoprotein levels in blood serum and 500 mg/kg/day extract and 50 mg/ kg/day of steroidal fraction reversed liver biomarkers altered by INH in rats. In silico combined with experimental study identified the possible molecular mechanisms of C. pepo for the management of liver cirrhosis.
Key words: Cucurbita pepo; Hepatoprotective; Network Pharmacology; Molecular Dynamics; Isoniazid
|
