Effects of Mume Fructus extract on smoking-induced cough and TNBS-induced colitis in rats and its underlying mechanisms based on gut-lung body fluid metabolism.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Mume Fructus (MF) has been widely used in traditional Chinese medicine to alleviate chronic cough, diarrhea, and dysentery. Our previous studies confirmed that MF exerts beneficial effects on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. However, the active components of MF and underlying mechanisms by which it alleviates both cough and colitis remain incompletely understood. AIM OF THE STUDY: This study aims to further elucidate the active components of MF and underlying mechanisms for alleviating both cough and colitis. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to analyze the chemical profiles of MF ethanol extract and its fractions (MFE0, MFE40, and MFE100). A rat model was established through simultaneous cigarette smoke exposure and TNBS enema administration to evaluate the ameliorative effects of these fractions on both cough and colitis. Molecular docking was combined with western blotting to investigate the underlying mechanisms. RESULTS: Among the three fractions of MF, MFE40 and MFE100 significantly reduced cough frequency and pulmonary edema, ameliorated colon shortening, and alleviated pathological damage in the lungs and colon of model rats. In contrast, MFE0 showed limited efficacy against cough and pulmonary edema. UPLC-Q-TOF-MS/MS identified key compounds in MFE40 and MFE100-including citric acid derivatives, hydroxycinnamic acid derivatives, flavonoids, unsaturated fatty acids, and terpenoids-which exhibited strong binding affinity to TLR4, AQP5, αENaC, TRPV1, and Na/K-ATPase in molecular docking analysis. Western blotting confirmed that MFE40 and MFE100 modulated expression of αENaC, TLR4, AQP5, and AQP3 in lung and colon tissues, suggesting these fractions improve cough and colitis by regulating body fluid metabolism and reducing inflammation. CONCLUSION: MFE40 (primarily citric acid and hydroxycinnamic acid derivatives) and MFE100 (mainly flavonoids, unsaturated fatty acids, and terpenoids) alleviated smoking-induced cough and TNBS-induced colitis in rats. These effects are mediated through TLR4 regulation and the activation of AQPs and ENaC, which together regulate body fluid metabolism and mitigate inflammatory injury in the lungs and intestines. This study elucidates the active components and underlying mechanisms of MF in mitigating cough and colitis, providing scientific evidence for the clinical application of MF in managing IBD and its extraintestinal manifestations.