Zhang Zhengxu, Ouyang Lishan, Sun An, Pu Zongjin, Liu Yixin, Peng Ying, Li Xiaobo
School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.
J Ethnopharmacol. 2025 Sep 13;355(Pt A):120539. doi: 10.1016/j.jep.2025.120539.
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.
This study aims to further elucidate the active components of MF and underlying mechanisms for alleviating both cough and colitis.
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.
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.
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.
乌梅在传统中药中已被广泛用于缓解慢性咳嗽、腹泻和痢疾。我们之前的研究证实，乌梅对2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠炎症性肠病（IBD）具有有益作用。然而，乌梅的活性成分及其缓解咳嗽和结肠炎的潜在机制仍未完全明确。
本研究旨在进一步阐明乌梅的活性成分及其缓解咳嗽和结肠炎的潜在机制。
采用超高效液相色谱-四极杆飞行时间串联质谱（UPLC-Q-TOF-MS/MS）分析乌梅乙醇提取物及其馏分（MFE0、MFE40和MFE100）的化学图谱。通过同时暴露于香烟烟雾和TNBS灌肠建立大鼠模型，以评估这些馏分对咳嗽和结肠炎的改善作用。分子对接与蛋白质免疫印迹相结合以研究潜在机制。
在乌梅的三个馏分中，MFE40和MFE100显著降低咳嗽频率和肺水肿，改善结肠缩短，并减轻模型大鼠肺和结肠的病理损伤。相比之下，MFE0对咳嗽和肺水肿的疗效有限。UPLC-Q-TOF-MS/MS鉴定出MFE40和MFE100中的关键化合物，包括柠檬酸衍生物、羟基肉桂酸衍生物、黄酮类、不饱和脂肪酸和萜类化合物，这些化合物在分子对接分析中对TLR4、AQP5、αENaC、TRPV1和Na/K-ATP酶表现出强烈的结合亲和力。蛋白质免疫印迹证实，MFE40和MFE100调节肺和结肠组织中αENaC、TLR4、AQP5和AQP3的表达，表明这些馏分通过调节体液代谢和减轻炎症来改善咳嗽和结肠炎。
MFE40（主要为柠檬酸和羟基肉桂酸衍生物）和MFE100（主要为黄酮类、不饱和脂肪酸和萜类化合物）减轻大鼠吸烟诱导的咳嗽和TNBS诱导的结肠炎。这些作用是通过TLR4调节以及水通道蛋白（AQPs）和上皮钠通道（ENaC）的激活介导的，它们共同调节体液代谢并减轻肺和肠道的炎症损伤。本研究阐明了乌梅减轻咳嗽和结肠炎的活性成分及潜在机制，为乌梅在治疗IBD及其肠外表现的临床应用提供了科学依据。
