OBJECTIVET To explore the impact of ononin on radiation-induced gastrointestinal inflammation in mice harboring tumors, as well as elucidate the underlying mechanisms.

METHODS  Forty male C57BL/6 mice(18−22 g) were subjected to random allocation into blank group, tumor group, radiation group, and ononin group. With the exception of the blank group, the remaining mice were subcutaneously administered Lewis lung cancer cells in the left axilla. Once the lung tumors reacheda diameter of approximately 3−6 mm, the radiation group and cynandione A group were subjected to X-ray irradiation at a dosage of 4 Gy for a duration of 2 min. Following successful model establishment, the ononin group received intraperitoneal administrations of ononin for a duration of 3 d. Subsequent to sampling, histopathological morphology of colon tissue was assessed via hematoxylin-eosin(HE) staining. ELISA was employed to determine the levels of IL-33, TNF-α, IL-1β, and IL-6, while immunohistochemistry was employed to track ST2L expression. Notably, immunofluorescence was utilized to monitor TRPA1 expression, and Western blotting was conducted to evaluate the expression levels of ST2L, TRPA1, P-PLCγ, and IP3R proteins.

RESULTS  Compared with post-irradiation, ononin administration significantly improved colon tissue damage(P<0.01), decreased IL-33 levels in lung tissue(P<0.05), downregulated the expression of ST2L, TRPA1, P-PLCγ, and IP3R proteins(P<0.01 or P<0.001), and reduced the levels of inflammatory factors TNF-α, IL-1β, and IL-6 in the serum(P<0.01 or P<0.001).

CONCLUSION Ononin effectively mitigates radiation-induced intestinal inflammation in lung cancer by inhibiting the expression of IL-33, thereby suppressing the subsequent activation of TRPA1 channels.