The Effectiveness of Hydroalcoholic Extract and Fraction of Cucumis melo on Amelioration of High Fat Diet Induced hepatotoxicity: A Comprehensive Approach Integrating Computational and Preclinical Validation

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is most prevalent global health problem, develops due to accumulation lipids in the hepatocytes in the form of Triglycerides (TG) and Free Fatty Acids (FFA). Traditional healers recommend seeds of Cucumis melo Linn as a liver tonic as well as for its treatment of liver cirrhosis, however its hepatoprotective mechanism have not been explored. Objectives: To investigate significant molecular mechanism of C. melo against liver cirrhosis via in vivo analysis followed by in silico. Materials and Methods: HFD was used for the induction of hepatotoxicity in mice and Silymarin as a standard control. The physical parameters were measured throughout the study along with antioxidant, serum biomarkers and histology of liver. Further, System biology tools were used to predict the possible mechanism of action. Docking studies were carried out with modulated phytocompounds against FXR protein target. Results: C. melo. Extract and fraction ameliorated the HFD induced oxidative stress and histological changes. Additionally, improved liver biochemical parameters such as AST, ALT, ALP, serum bilirubin, total bilirubin, LDL, VLDL, TC and, TP were seen remarkable significant effects. Furthermore, System biology revealed the 16 phytocompounds of C. melo Linn. potentially regulate the PPAR signaling. Among them, Euphol phytocompound was predicted to interact with secreted FXR and may contribute to reduced hepatotoxicity. Conclusion: The results suggests C. melo as a promising therapeutic agent for hepatotoxicity by reducing the symptoms and stress associated with diseases condition which may be due to the regulation of multiple protein via multiple phytocompounds.