Exploring Pigeon Pea (Cajanus cajan) as a Functional Food: Nutritional Profile, Bioactive Compounds, and Enzyme Inhibition for Glycemic Control

Diabetes mellitus remains a global health challenge, necessitating dietary strategies to complement pharmacological interventions. Cajanus cajan (pigeon pea), an underutilized legume, shows promise as a functional food for glycemic control, yet mechanistic links between its phytochemicals and the inhibition of dipeptidyl-peptidase-4 (DPP4) and protein tyrosine phosphatase 1B (PTP1B) remain under-explored. This study evaluated the nutritional composition, bioactive compounds, and interactions of C. cajan with diabetes-related enzymes (DPP4 and PTP1B) through proximate analysis, LC-HRMS, molecular docking, and dynamics simulations. Proximate analysis confirmed high protein (20.42%), dietary fiber (5.03%), and essential minerals (Ca 1298 ppm; Fe 44.1 ppm; Zn 32.3 ppm). LC-HRMS identified flavonoids such as diosmetin, genistein, and naringenin, known for potential antidiabetic properties. Molecular docking demonstrated strong binding affinities of diosmetin to DPP4 (−8.18 kcal/mol) and genistein to PTP1B (−8.212 kcal/mol), surpassing control inhibitors (−7.965 kcal/mol for DPP4 and −8.770 kcal/mol for PTP1B). Molecular dynamics simulations over 50 ns confirmed stable interactions, with diosmetin–DPP4 and genistein–PTP1B complexes exhibiting low backbone RMSD (≤2.5 Å) and sustained hydrogen bonding. ADMET predictions highlighted moderate bioavailability (0.51–0.777) for key compounds but flagged hepatotoxicity risks (0.541–0.766), mitigated by dietary matrix effects. Although most screened compounds exhibited short half-lives and potential for CYP-mediated drug interactions, these concerns are likely mitigated by other nutritional components, supporting the overall excellent functional food properties. These findings suggest that C. cajan modulates glycemic control via enzyme inhibition and oxidative stress reduction. The study underscores C. cajan’s potential as a natural dietary intervention for diabetes management, warranting clinical validation.