6-Shogaol from Banxia Xiexin Tang: A Potent Regulator of Th17/Treg Balance to Protect Against CPT-11-Induced Intestinal Mucosal Damage

Irinotecan (CPT-11)-induced intestinal mucosal injury is a common complication of chemotherapy, significantly affecting gastrointestinal health. This study aimed to explore the potential therapeutic effects of 6-shogaol, a key component of Banxia Xiexin Tang (BXXXT), on regulating the T helper 17 cells (Th17)/regulatory T cells (Treg) balance to alleviate CPT-11-induced intestinal mucosal injury in rats. Rats were treated with CPT-11 to induce intestinal mucosal injury and subsequently exposed to 6-shogaol or BXXXT. Body weight, disease activity index (DAI), and histopathological changes in the small intestine were assessed. Biomarkers of intestinal injury, including D-lactic acid, diamine oxidase (DAO) and endotoxin, were measured. Enzyme-linked immunosorbent assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate inflammatory cytokine levels in serum and small intestine tissues. Through flow cytometry, RT-qPCR and Western blot, the Th17/Treg balance was examined. Both 6-shogaol and BXXXT significantly alleviated CPT-11-induced intestinal mucosal injury, as demonstrated by increased body weight, reduced DAI, and improved histopathological results. Both treatments decreased the levels of intestinal damage-related biomarkers (D-lactic acid, DAO, and endotoxin) and suppressed the inflammatory response. Furthermore, 6-shogaol treatment restored the Th17/Treg balance by decreasing the proportion of Th17 cells and increasing the number of Treg cells. Collectively, 6-shogaol, a major component of Banxia Xiexin Tang, effectively regulates the Th17/Treg balance and attenuates CPT-11-induced intestinal mucosal injury in rats, signifying that 6-shogaol holds therapeutic potential for preventing and curing chemotherapy-induced gastrointestinal damage.