Comparative phytochemical profiling and molecular docking-based evaluation of the antidiabetic potential of cola cordifolia and cola millenii

Diabetes mellitus is a metabolic disorder with chronic hyperglycemia and oxidative stress as core features. The disease is also characterized by inflammatory responses, dyslipidemia, and damage to several organs and tissues. Due to the detrimental effects of most of the available antidiabetic agents, there has been a growing interest in exploring medicinal plants as alternative sources of therapeutic agents. This article aimed to evaluate the antidiabetic and antioxidant potentials of Cola millenii and Cola cordifolia through the identification of phytoconstituents with high predicted efficacy toward selected molecular targets and favorable pharmacokinetics to warrant their biological evaluation. The leaves of C. millenii and C. cordifolia were extracted by cold maceration with absolute ethanol. The extracts were assessed for α-amylase and α-glucosidase inhibitory activities, ferric reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, and inhibition of lipid peroxidation. Gas chromatography-mass spectrometry (GC-MS) was performed to identify the phytoconstituents present in the extracts. The interactions of the phytoconstituents were predicted with human pancreatic α-amylase and human lysosomal acid α-glucosidase. Docking scores, protein–ligand interaction, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, drug-likeness, target prediction, and pathway enrichment analysis were determined for the selected phytoconstituents. The GC-MS analysis revealed the presence of forty-two and thirty-two phytoconstituents in C. millenii and C. cordifolia extracts, respectively. The identified phytochemicals belonged to different classes of metabolites, including fatty acids, hydrocarbons, terpenoids, esters, and lignans. Notably, sesamin was found in both species; however, squalene was unique to C. millenii . Both extracts showed α-amylase and α-glucosidase inhibitory activities and radical scavenging activities. Overall, C. millenii extract showed higher antioxidant potential than C. cordifolia extract. Molecular docking analysis revealed favorable binding interactions of selected phytoconstituents with α-amylase and α-glucosidase. Sesamin exhibited the highest binding affinity to α-amylase among the selected phytochemicals from C. millenii with a binding energy of −9.4 kcal/mol. Cholest-2-ene-2-methanol (5α) and sesamin showed the highest binding affinity to α-glucosidase with binding energies of −9.3 kcal/mol each, compared to −7.0 kcal/mol of acarbose. The protein–ligand interaction analysis revealed that the selected phytoconstituents interacted favorably with amino acid residues in the active site of the target enzymes. The ADMET profile and drug-likeness prediction results revealed that the selected phytochemicals from the two Celastraceae species had desirable pharmacokinetic properties. The target prediction and pathway enrichment analysis revealed that the selected phytochemicals could modulate multiple molecular targets and pathways involved in the various physiological functions related to glucose metabolism and oxidative stress. This study established the antidiabetic and antioxidant potentials of C. millenii and C. cordifolia through the identification of phytochemicals with favorable efficacy toward selected molecular targets and pharmacokinetics profiles