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 methanol leaf and stem extracts of I. aquatica against CCl 4 -induced hepatotoxicity in Wistar albino rats. Supported by GC–MS phytochemical profiling, in silico docking, ADMET, toxicity prediction, and molecular flexibility simulation against fibrosis. 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 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 73 phytoconstituents obtained from GC-MS analysis, four (CID 110680, 162265, 10297 and 5367692) represent predicted binding affinities ( ≤ − 6.0 kcal/mol) against 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 future mechanistic and clinical exploration of I. aquatica as a potential hepatoprotective natural product candidate.