Senna petersiana inhibits key digestive enzymes and modulates dysfunctional enzyme activities in oxidative pancreatic injury

Abstract

Objective: To evaluate the effect of Senna petersiana leaf extracts on key digestive enzymes and FeSO4-induced oxidative injury. Methods: Dried Senna petersiana leaf powder (60 g) was defatted in n-hexane and then extracted sequentially at room temperature with dichloromethane, methanol, and distilled water. The total phytochemical content of the extracts was estimated using established methods. The in vitro antioxidant, anti-lipase, and antidiabetic activities and the effect of the extracts on intestinal glucose absorption and FeSO4-induced pancreatic oxidative injury were determined using different protocols. Moreover, GC-MS analysis was performed to identify the main compounds of the plant extract. Molecular docking analysis was also carried out to evaluate the binding energy of compounds with digestive enzymes. Results: Senna petersiana leaf extracts showed significant antioxidant activities in FRAP, DPPH, and hydroxyl radical scavenging assays. They also inhibited pancreatic lipase and lowered intestinal glucose absorption by suppressing activities of α-amylase and α-glucosidase. Treatment with the extracts also lowered lipid peroxidation (malondialdehyde), nitric oxide level, acetylcholinesterase, and ATPase activities with simultaneous improvement of antioxidant (catalase, superoxide dismutase, glutathione) capacity in the type 2 diabetes model of oxidative pancreatic injury. GC-MS characterization of the extracts revealed the presence of stilbenoids, alkaloids, and other compounds. Molecular docking screening assay indicated the extract phytochemicals showed strong interaction with the active site amino acids of the targeted digestive enzymes. Among the Senna petersiana compounds, veratramine had the highest affinity for α-amylase and lipase, whereas dihydrostilbestrol was most attracted to α-glucosidase. Conclusions: Senna petersiana inhibits carbohydrate digestive enzymes, reduces intestinal glucose absorption, and exerts ameliorative effects on FeSO4-induced oxidative pancreatic injury with significant antioxidant capabilities. Detailed in vivo studies are underway to understand the plant's therapeutic potential in diabetes management.