Citric Acid‑Assisted Microwave Degradation of Hericium erinaceus β‑Glucan Enhances Gastroprotective Efficacy

The gastroprotective bioactivity of high molecular‐weight β‐glucan from Hericium erinaceus is often constrained by its poor solubility and low oral bioavailability. Herein, a citric acid‐assisted microwave degradation strategy was employed to obtain β‐glucans with higher gastroprotective activity. Among them, a specific fraction (CAMS6) displayed discrete spherical or quasi‐spherical particles and significantly alleviated ethanol‐induced gastric injury, reflecting in improving oxidative stress in gastric tissues and reducing the ulcer index by 50.44% in the high‐dose group of CAMS6. Concurrently, CAMS6 restored immune homeostasis of damaged gastric mucosa by inhibiting Th1 response and activating Th2 response, as evidenced by the shift of regulated biomarker (T‐bet, IL‐1α, IL‐3, tumor necrosis factor alpha [TNF‐α], GATA‐3, IL‐9, IL‐10, IL‐13) levels to baseline levels. Mechanistic investigations revealed that the gastroprotective effect of CAMS6 was mediated through modulation of the EGFR–ERK signaling pathway. Conclusively, this study provides an effective degradation strategy to enhance the therapeutic potential of H. erinaceus β‐glucan for gastric protection.