COMPUTATIONAL EVALUATION OF BIOACTIVE CONSTITUENTS FROM AQUEOUS AND ETHANOL EXTRACTS OF CHROMOLAENA ODORATA AND VERNONIA AMYGDALINA WITH ANTIOXIDANT, ANTIDIABETIC, AND ANTIHYPERTENSIVE POTENTIALS

The increased cases of diabetes and hypertension in sub-Saharan Africa provide a rationale for the need for cost-effective and multi-target therapeutic agents. The in-silico methodology was employed to elucidate the molecular interactions, drug-likeness, and pharmacokinetic characteristics of bioactive compounds from aqueous and ethanol extracts of Chromolaena odorata and Vernonia amygdalina. Key phytochemicals such as luteolin, apigenin, quercetin, and chlorogenic acid were retrieved from literature and PubChem databases and docked against α-amylase, α-glucosidase, and angiotensin-converting enzyme (ACE) using AutoDock Vina. Luteolin and apigenin demonstrated strong binding affinities, forming stable hydrogen bonding and hydrophobic interactions with α-glucosidase (−8.4 kcal/mol) and ACE (−9.1 kcal/mol), respectively. Notably, cepharanthine exhibited the highest binding affinity (−12.195 kcal/mol against ACE and −10.553 kcal/mol against DPP-4), although its pharmacokinetic profile was less favorable. Comparative docking analysis revealed that ethanol extracts exhibited stronger binding interactions than aqueous extracts, as reflected by more negative binding energies such as cynaroside (−9.572 kcal/mol) and longiverbenone (−8.492 kcal/mol) against ACE, compared to weaker interactions observed for aqueous-associated compounds like glucurolactone (−5.741 kcal/mol) and neomenthol (−5.863 kcal/mol). This enhanced activity is attributable to the higher abundance of phenolic and flavonoid constituents in ethanol extracts. SwissADME and Protox-II predictions further demonstrated favorable ADMET properties, with most compounds showing high gastrointestinal absorption, bioavailability scores of 0.55, and minimal Lipinski rule violations (0–1). Toxicity profiling indicated low toxicity, with LD₅₀ values ranging from 940 to 10,700 mg/kg and classification within toxicity classes IV–VI. Importantly, compounds such as apigenin and cynaroside were predicted to be non-hepatotoxic, non-mutagenic, and non-carcinogenic, supporting their safety profiles. Conclusively, the findings mechanistically justify the ethnomedicinal applications of C. odorata and V. amygdalina and highlight their potential as sources of multi-target antioxidant, antidiabetic, and antihypertensive agents. The integration of molecular docking with pharmacokinetic profiling provides a rational framework for identifying bioactive lead compounds, which can be further validated experimentally and developed into phytopharmaceuticals.