6‐Shogaol from Dried Ginger Protects against Intestinal Ischemia/Reperfusion by Inhibiting Cell Apoptosis via the BDNF/TrkB/PI3K/AKT Pathway

Scope Intestinal ischemia‐reperfusion (II/R) injury is a common pathological process with high morbidity and mortality. Effective prevention and treatment therapies for II/R are clinically necessary. 6‐Shogaol (6‐SG), the main active ingredient in dried ginger, behaviors multiple biological activities, including anti‐inflammation, antioxidation, and anti‐apoptosis. This study aims to elucidate the protective effects and mechanism of 6‐SG against II/R‐induced injury. Methods and results Sprague‐Dawley rats are pre‐treated orally with 6‐SG and subjected to II/R injury by clamping superior mesenteric artery for 1 h and reperfusion for 2 h. Caco‐2 cells are challenged by hypoxia/reoxygenation to mimic II/R in vitro. 6‐SG pre‐treatment protects against II/R injury by reducing intestinal morphological damage and intestinal barrier injury via inhibiting cell apoptosis. Network pharmacology and molecular docking analyses reveal that 6‐SG has a high affinity with brain‐derived neurotrophic factor (BDNF) formed homodimer or heterodimer with NT4 instead of the monomer, and thus the dimer configuration is stabilized, activating BDNF/TrkB/PI3K/AKT signaling pathway and inhibiting II/R‐induced cell apoptosis. The outcome is further validated both in vivo and in vitro. Conclusion 6‐Shogaol protects against II/R injury by inhibiting cell apoptosis through the BDNF/TrkB/PI3K/AKT pathway. This study offers a new understanding of the protection mechanism of 6‐SG against II/R‐induced injury.