Betulinic acid attenuates cyclophosphamide-induced intestinal mucosa injury by inhibiting the NF-kappa B/MAPK signalling pathways and activating the Nrf2 signalling pathway

文献类型： 外文期刊

第一作者： Ou, Zhaoping

作者： Ou, Zhaoping;Zhu, Lijuan;Huang, Chenglong;Ma, Chaoyang;Kong, Li;Lin, Xing;Gao, Xinyu;Huang, Lin;Wen, Lixin;Yuan, Zhihang;Wu, Jing;Yi, Jine;Liang, Zengenni

作者机构：

关键词： Betulinic acid; Cyclophosphamide; Intestinal mucosal barrier dysfuction; NF-kappa B/MAPK pathways; Nrf2 pathway

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.291； 五年影响因子：6.393 ）

ISSN： 0147-6513

年卷期： 2021 年 225 卷

页码：

收录情况： SCI

摘要： Betulinic acid (BA), a pentacyclic triterpenoid, has been associated with several biological effects, such as antioxidant, anti-inflammatory and antiviral activities. Previous studies have demonstrated that BA has the ability to alleviate intestinal mucosal damage, however, the potential mechanism associated with the effect has not been reported. This study aimed to investigate the possible protective mechanism of BA against cyclophosphamide (CYP)-induced intestinal mucosal damage. Here, we found that BA pretreatment prevented intestinal mucosal barrier dysfuction from CYP-challenged mice by repairing the intestinal physical, chemical, and immune barriers. Moreover, BA treatment suppressed the CYP-induced oxidative stress by activating the nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) pathway blocked reactive oxygen species (ROS) accumulation. In addition, BA inhibited CYP-triggered intestinal inflammation through down-regulating the nuclear transcription factor kappa B (NF-kappa B)/mitogen-activating protein kinase (MAPK) pathways. Furthermore, BA pretreatment reduced intestinal apoptosis by blocking ROS-activated mitochondrial apoptotic pathway. Overall, the current study demonstrated the protective effect of BA against CYP-caused intestinal mucosal damage by regulating the Nrf2 and NF-kappa B/MAPK signalling pathways, which may provide new therapeutic targets to attenuate intestinal impairment and maintain intestinal health.

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