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

Abstract

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. Sprague-Dawley rats are pre-treated orally with 6-SG and subjected to II/R injury by clamping superior mesenteric artery for 1h and reperfusion for 2h. 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 revealthat 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. 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.