GC–MS profiling, in silico modeling and hepatoprotective activity of Ipomoea aquatica Forsk against CCl4-induced hepatotoxicity in Wistar rats

Abstract Ipomoea aquatica possesses high flavonoid and polyphenol content, with pharmacological applications as a liver tonic for digestive disorders, diabetes, and inflammation. The objective of the present study is to investigate the hepatoprotective activity of methanolic leaf and stem extracts of I. aquatica against CCl 4 -induced hepatotoxicity in Wistar albino rats. Additionally, this study was supported by GC–MS phytochemical profiling, in silico docking, ADMET, toxicity prediction, and molecular flexibility simulation. CCl 4 -treated rats showed a restoration of hematological parameters, markers for liver function (ALP, SGPT, SGOT and bilirubin) and changes in hepatic histology as compared to controls after treatment with both extracts ( p < 0.01), restoring the values at the high dose leaf (700 mg/kg) or stem extract (500 mg/kg) to values similar to or ≤ values obtained with silymarin in some cases. Among the 52 phytoconstituents tentatively identified from GC-MS analysis, four (CID 110680, 162265, 10297 and 5367692) compounds exhibited predicted binding affinities ( ≤ − 6.0 kcal/mol) against the TGF-β type I receptor, in which CID 110680 showed the best score of − 6.9 kcal/mol, close to silymarin (-7.0 kcal/mol). Stability of the ligand-receptor complex conformations for all four hits was supported by CABS-flex simulation, confirming the predicted binding modes. The results support the further mechanistic and pharmacological exploration of I. aquatica as a potential hepatoprotective natural product candidate.