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一水合岩白菜素通过丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路减轻感染引起的炎症反应。

Bergenin Monohydrate Attenuates Inflammatory Response via MAPK and NF-κB Pathways Against Infection.

作者信息

Tang Qihe, Wang Qingyu, Sun Zhuojian, Kang Songyao, Fan Yimeng, Hao Zhihui

机构信息

Agricultural Bio-pharmaceutical Laboratory, Qingdao Agricultural University, Qingdao, China.

College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.

出版信息

Front Pharmacol. 2021 May 4;12:651664. doi: 10.3389/fphar.2021.651664. eCollection 2021.

Abstract

has emerged as a critical pathogen causing severe clinical problems, such as pneumonia and sepsis. Meanwhile, intensified drug resistance induced by antibiotic therapy necessitates discovering novel and active molecules from Traditional Chinese Medicine (TCM) for treatment. In this study, the isolated Bergenin monohydrate showed an anti-inflammatory effect in Klebsiella-infected mice. We initially investigated the anti-inflammatory effects and cytoprotection against oxidative stress and . Interestingly, a specific dose of Bm can effectively ameliorate lung injury and suppress the expression of inflammatory cytokines such as TNF-α, IL-6, IL-1β and PEG2. Moreover, Bm was also shown to reduced the levels of MPO, MDA and increased SOD and GSH activities. Moreover, we assessed the intracellular signaling molecules including p38, ERK, JNK, IκB, NF-κB-p65 by western blotting and verified through MAPK and NF-κB pathways inhibition experiments. These results reveal that Bm executed its effects via the classical MAPK signaling pathway and NF-κB pathway. Given its underlying anti-inflammatory effect, Bm may be used as a promising therapeutic against Klebsiella-induced infection, thus providing a benefit for the future clinical therapy of pneumonia and medicine design.

摘要

已成为引起严重临床问题的关键病原体,如肺炎和败血症。与此同时,抗生素治疗导致的耐药性增强使得有必要从中药中发现新的活性分子用于治疗。在本研究中,分离得到的一水岩白菜素在感染克雷伯菌的小鼠中显示出抗炎作用。我们最初研究了其抗炎作用以及对氧化应激的细胞保护作用。有趣的是,特定剂量的一水岩白菜素可以有效改善肺损伤并抑制炎症细胞因子如肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β和前列腺素E2的表达。此外,一水岩白菜素还能降低髓过氧化物酶、丙二醛水平,并提高超氧化物歧化酶和谷胱甘肽活性。此外,我们通过蛋白质印迹法评估了包括p38、细胞外信号调节激酶、应激活化蛋白激酶、核因子κB抑制蛋白、核因子κB p65在内的细胞内信号分子,并通过丝裂原活化蛋白激酶和核因子κB途径抑制实验进行了验证。这些结果表明,一水岩白菜素通过经典的丝裂原活化蛋白激酶信号通路和核因子κB途径发挥作用。鉴于其潜在的抗炎作用,一水岩白菜素可能作为一种有前景的治疗药物用于对抗克雷伯菌引起的感染,从而为未来肺炎的临床治疗和药物设计提供帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1704/8129520/2106441af2bf/fphar-12-651664-g001.jpg

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