Undaria pinnatifida (Wakame) Attenuates Hyperglycemia-dysregulated Signaling and Metabolic Enzyme Activities in Isolated Rat Jejunum: An ex vivo and in silico Investigation

Background/Objectives: Diabetes mellitus is associated with impaired glucose metabolism and dysregulated metabolic signaling pathways. This study aimed to evaluate the potential of Undaria pinnatifida extracts to inhibit intestinal glucose absorption and modulate related biochemical pathways using an ex vivo experimental model. Methods: Freshly isolated rat jejunum tissues were incubated with glucose and varying concentrations of aqueous and ethanol extracts of U. pinnatifida for 2 hours at 37 ℃. Acarbose was used as a positive control. Biochemical assays were conducted to examine glucose absorption, ATPase activity, glutathione metabolism, digestive enzyme activity, and key metabolic regulators. In silico molecular docking was also performed to evaluate the interactions of identified phytoconstituents with sodium glucose co-transporter 1 (SGLT1). Results: Exposure to high glucose levels significantly increased jejunal glucose absorption, reduced ATPase activity, disrupted glutathione metabolism, and elevated digestive enzyme activity and metabolic regulators, including acetylcholinesterase, Ectonucleoside Triphosphate Diphosphohydrolase (ENTPDase), glucose-6-phosphatase (G-6-Pase), fructose-1,6-bisphosphatase (F-1,6-Bpase), and glycogen phosphorylase. Treatment with U. pinnatifida extracts reversed most of these dysregulations. In silico analysis further revealed that fucoxanthinol, among other phytoconstituents, showed a higher binding affinity to SGLT1 compared to Sotagliflozin, a clinically approved inhibitor. Conclusion: U. pinnatifida extracts demonstrated the ability to modulate glucose absorption and restore dysregulated intestinal biochemical parameters. These findings support the therapeutic potential of this seaweed in managing intestinal dysregulation in diabetic conditions.