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广藿香烯环氧化物对大鼠乙醇诱导型胃溃疡的预防作用:对氧化应激、炎症和细胞凋亡的影响

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.

作者信息

Liang Jiali, Dou Yaoxing, Wu Xue, Li Huilin, Wu Jiazhen, Huang Qionghui, Luo Dandan, Yi Tiegang, Liu Yuhong, Su Ziren, Chen Jianping

机构信息

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

出版信息

Chem Biol Interact. 2018 Mar 1;283:30-37. doi: 10.1016/j.cbi.2018.01.014. Epub 2018 Jan 12.

DOI:10.1016/j.cbi.2018.01.014
PMID:29339218
Abstract

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.

摘要

广藿香环氧物(PAO)是从长期储存的广藿香油中分离出的一种三环倍半萜,根据我们之前的研究,它已在体内被证明具有抗炎活性。然而,PAO的胃保护作用仍然未知。因此,在本研究中,我们建立了乙醇诱导的胃溃疡模型,以评估PAO的抗溃疡活性,并阐明其潜在机制。根据我们的结果,宏观检查显示,与载体组相比,PAO可显著减少乙醇诱导的胃溃疡面积,组织学评估结果也支持这一点。至于其潜在机制,PAO的抗炎活性通过逆转促炎细胞因子和抗炎细胞因子之间的失衡以及调节NF-κB途径相关蛋白(包括p-IκBα、IκBα、p-p65和p65)的表达来促进胃保护。此外,PAO能够增强抗氧化酶(包括谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT))的表达,并下调脂质过氧化指标丙二醛(MDA)。此外,免疫组织化学分析显示PAO具有强大的抗凋亡作用,下调caspase-3、Fas和Fasl的蛋白表达可作为证据。此外,我们还证明PAO可以补充PGE和NO黏膜防御。总之,这些发现表明PAO对乙醇具有胃保护活性,这可能与其对炎症反应、氧化应激、凋亡级联反应和胃黏膜防御的影响有关。

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