Molecular Modelling and Biochemical Investigation of Aspilia Africana on Oxido-inflammatory and Apoptotic Responses in Phenanthrene-induced Cadiorenal Toxicity in Rats

The widespread environmental exposure to phenanthrene (PHE), a polycyclic aromatic hydrocarbon (PAH), presents a significant toxicological concern, particularly for the heart and kidney, through mechanisms involving oxidative stress, inflammation, and apoptosis. This study investigated the protective effects of Aspilia africana (AA) aqueous extract and chrysin against PHE-induced cardiorenal toxicity in rats, and further explored their molecular interactions and pharmacokinetic properties through in silico modelling. Cardiorenal toxicity was induced by oral administration of PHE for 26 days, followed by treatment with AA (500 or 750 mg/kg) or chrysin (25 mg/kg) for 18 days. Serum and tissue biomarkers of renal and cardiac function, oxidative stress, inflammation, and apoptosis were evaluated. Molecular docking and ADMET analyses were performed using CB-Dock, Mcule, and SwissADME servers. PHE administration significantly elevated serum urea, creatinine, cystatin C, cardiac CK-MB, and troponins I and T, while reducing eGFR and antioxidant enzyme activities (SOD, CAT, GPx). Inflammatory cytokines (IL-1β, TNF-α) and pro-apoptotic markers (caspase-3, Bax, p53) were upregulated, whereas IL-10 and Bcl-2 were suppressed. Treatment with AA or chrysin markedly ameliorated these alterations. Docking revealed strong binding affinities (− 10.4 to − 7.5 kcal/mol) of seven AA bioactives—α-pinene, betulin, apigenin, caryophyllene, germacrene D, phytol, and quercetin—toward SGLT1 and GLP-1 receptors. ADMET profiling indicated favourable drug-likeness, high gastrointestinal absorption, and low toxicity. These findings suggest that Aspilia africana confers potent cardiorenal protection against phenanthrene-induced toxicity by attenuating oxidative stress, inflammation, and apoptosis, supported by computational validation of its bioactive constituents.