Hunan Engineering Research Center of Livestock and Poultry Health Care, Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
Department of Hunan Agricultural Product Processing Institute, Changsha 410128, China.
Ecotoxicol Environ Saf. 2021 Dec 1;225:112746. doi: 10.1016/j.ecoenv.2021.112746. Epub 2021 Sep 2.
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-κB)/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-κB/MAPK signalling pathways, which may provide new therapeutic targets to attenuate intestinal impairment and maintain intestinal health.
白桦脂酸（BA）是一种五环三萜类化合物，与多种生物学效应有关，如抗氧化、抗炎和抗病毒活性。先前的研究表明，BA 具有减轻肠道黏膜损伤的能力，但与这种作用相关的潜在机制尚未报道。本研究旨在探讨 BA 对环磷酰胺（CYP）诱导的肠道黏膜损伤的可能保护机制。在这里，我们发现 BA 预处理通过修复肠道物理、化学和免疫屏障，防止 CYP 挑战的小鼠肠道黏膜屏障功能障碍。此外，BA 通过激活核因子红细胞 2 [NF-E2]-相关因子（Nrf2）途径阻止活性氧（ROS）积累，抑制 CYP 诱导的氧化应激。此外，BA 通过下调核转录因子 kappa B（NF-κB）/丝裂原激活蛋白激酶（MAPK）途径抑制 CYP 触发的肠道炎症。此外，BA 预处理通过阻断 ROS 激活的线粒体凋亡途径减少肠道细胞凋亡。总的来说，本研究通过调节 Nrf2 和 NF-κB/MAPK 信号通路，证明了 BA 对 CYP 引起的肠道黏膜损伤的保护作用，这可能为减轻肠道损伤和维持肠道健康提供新的治疗靶点。
