Evaluating the protective potential of Aspilia africana against phenanthrene-induced cardiorenal injury: biochemical and computational approaches.

UNLABELLED: Environmental exposure to phenanthrene (PHE), a polycyclic aromatic hydrocarbon, poses significant toxicological risks to vital organs, particularly the heart and kidney, through oxidative stress, inflammation, and apoptosis. This study evaluated the protective effects of Aspilia africana aqueous extract and chrysin against phenanthrene-induced cardiorenal toxicity in rats, while also exploring underlying molecular mechanisms using in silico approaches. Cardiorenal toxicity was induced by oral administration of phenanthrene for 26 days. Concurrent treatment groups received Aspilia africana (500 or 750 mg/kg) or chrysin (25 mg/kg). Renal and cardiac function biomarkers, oxidative stress indices, inflammatory cytokines, and apoptotic proteins were assessed in serum and tissue samples. Molecular docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were performed to evaluate interactions of selected Aspilia africana phytochemicals with sodium-glucose cotransporter-1 (SGLT1) and glucagon-like peptide-1 receptor (GLP-1R). Phenanthrene exposure significantly elevated serum urea, creatinine, cystatin C, creatine kinase-MB, and cardiac troponins I and T, while suppressing antioxidant enzymes (SOD, CAT, GPx). Pro-inflammatory cytokines (IL-1β, TNF-α) and pro-apoptotic markers (caspase-3, Bax, p53) were upregulated, whereas IL-10 and Bcl-2 were reduced. Co-administration of Aspilia africana or chrysin markedly reversed these alterations, restoring antioxidant balance and attenuating inflammatory and apoptotic responses. Molecular docking revealed favourable binding affinities of bioactive phytochemicals with SGLT1 and GLP-1R, while ADMET profiling indicated acceptable drug-likeness and low predicted toxicity for most compounds. This study suggests the multi-target protective potential of Aspilia africana against phenanthrene-induced cardiorenal toxicity, integrating in vivo biochemical evidence with in silico molecular interactions to provide mechanistic insight into its therapeutic relevance in environmental toxicology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00721-5.