Sennoside A from Cassia angustifolia as a mixed-type inhibitor of DPP-IV: Integrative in vitro, in silico, and kinetic characterization.

Type 2 diabetes mellitus represents a growing global health crisis, with India alone projected to surpass 124 million cases by 2040. Its multifactorial pathophysiology-including oxidative stress, insulin resistance, β-cell dysfunction, and impaired incretin signaling-is often inadequately addressed by existing therapies, which may lose efficacy and cause side effects over time. This highlights the need for safer, multi-targeted agents from natural sources. In this context, the present study explores the DPP-IV inhibitory and antioxidant potential of Cassia. angustifolia, focusing on its key constituent, sennoside A. The hydro-alcoholic extract showed notable DPP-IV inhibition (IC50 = 466.7 μg/mL), with HR-LCMS confirming abundant sennoside A, which exhibited stronger inhibition (IC50 = 138 μM) and a mixed-type kinetic profile. Molecular docking and dynamics revealed stable interactions with key DPP-IV residues (Glu205, Glu206, Tyr547, Tyr666), supported by favourable MM-GBSA energy (-36.00 ± 9.36 kcal/mol). ADMET predictions suggested good solubility and safety. Together, these findings position sennoside A as a promising natural DPP-IV inhibitor with complementary antioxidant properties for holistic type 2 diabetes management.