Xiaobanxia Decoction attenuates cisplatin-induced intestinal damage via restoring UFL1-mediated endoplasmic reticulum stress in a rat pica model

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Objective: Xiaobanxia Decoction (XBXD) is a traditional antiemetic formula effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its mechanism remains unclear. This study aimed to investigate whether it attenuates cisplatin-induced intestinal damage by restoring UFM1-specific ligase 1 (UFL1)-mediated endoplasmic reticulum stress (ERS) in a rat model of pica. Methods: Sixty-four 7-week-old male Sprague-Dawley rats were randomly assigned to four groups: control group, cisplatin model group, ondansetron-treated group, and XBXD-treated group ( n = 16 per group). A rat intestinal injury model was established by intraperitoneal injection of cisplatin. Kaolin intake was recorded every 24 hours. Histopathological examination was performed on the gastric antrum and ileum. Serum levels of reactive oxygen species, interleukin-6, tumor necrosis factor-α, diamine oxidase, lipopolysaccharide, and Mucin2 in the ileum were measured using enzyme-linked immunosorbent assay. Immunohistochemistry and immunoblotting were used to measure protein levels of Claudin-1, Occludin, UFL1, IRE1, p-IRE1, XBP1, Bip, and CHOP in the ileum. Results: XBXD improved pica behavior in cisplatin-treated rats and ameliorated gastrointestinal inflammatory injury. XBXD reduced the elevated serum levels of reactive oxygen species, interleukin-6, tumor necrosis factor-α, diamine oxidase, and lipopolysaccharide (all P < 0.01) induced by cisplatin. XBXD also reversed the significant decrease in Mucin2 expression ( P < 0.05, P < 0.01, respectively) in the rat ileum caused by cisplatin. The decreased expression of Claudin-1 and Occludin ( P < 0.01 in Occludin 24 and 72 hours; P < 0.05 in Claudin-1 24 and 72 hours) induced by cisplatin was alleviated by XBXD treatment. In the ileum, XBXD restored UFL1 expression ( P < 0.01 in 24 hours; P < 0.05 in 72 hours) and regulated cisplatin-induced ERS. Conclusion: XBXD attenuates cisplatin-induced intestinal damage, possibly by restoring UFL1-mediated ERS.

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