Chlorogenic Acid Alleviates Chronic Stress-Induced Ileal Oxidative Stress and Apoptosis in Rats by Influencing Intestinal Flora and Activating Nrf2 Pathway

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Background: Chronic stress is implicated in the pathogenesis of gastrointestinal disorders, with reactive oxygen species (ROS) contributing significantly. Chlorogenic acid (CGA), a polyphenolic compound, exhibits antioxidant properties. This study investigated whether CGA mitigates ROS-mediated oxidative stress and apoptosis in chronic stress-induced ileal injury. Methods: Rats were subjected to restraint stress for 21 days, with/without CGA (100 mg/kg, gavage). CGA’s mechanism was elucidated by assessing ileal flora, oxidative stress markers, apoptosis, structural changes, and the Nrf2 pathway. Results: CGA restored ileal structure, attenuated ROS and MDA levels, elevated GSH and SOD levels, and reduced apoptosis-associated proteins. CGA stabilized conformation bound to Keap1, deregulating Keap1’s negative regulation of Nrf2, thereby increasing Nrf2 and downstream protein expression (HO-1 and NQO1). Gut microbiota imbalance was corrected, with increased Lactobacillus abundance post-CGA intervention. Conclusions: CGA alleviates chronic stress-induced ileal oxidative stress and apoptosis, which relates closely to Nrf2 pathway activation and modulation of intestinal microflora.

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