Shen Yongmei, Sun Jia, Niu Chao, Yu Dongdong, Chen Zhiwei, Cong Weitao, Geng Funeng
Sichuan Key Laboratory of Medical American Cockroach, Chengdu, China.
College of Pharmacy, Wenzhou Medical University, Wenzhou, China.
Chem Biol Interact. 2017 Aug 1;273:115-124. doi: 10.1016/j.cbi.2017.06.007. Epub 2017 Jun 9.
This study was designed to evaluate the gastroprotective effect of Kangfuxin (KFX), a Chinese patent medicine constituent isolated from American cockroach, on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the effect involved. According to the results, mice treated with alcohol appeared obvious gastric mucosal injury, while treatment with Cimetidine (a positive control) and KFX significantly relieved the damage, along with decreased oxidative stress and apoptosis indexes. Subsequently, we conducted a label-free quantitative proteomic (LFQ) and found that NF-κB and PI3K/AKT signaling pathway participated in gastroprotective effect of KFX. Furthermore, Western blot analysis revealed that KFX treatment inhibited the expression of TNF-α, IL-1β, greatly reduced the phosphorylation level of IκB and repressed the nuclear translocation of NF-κB p65, which demonstrated that KFX inhibited the activation of NF-κB pathway. Meanwhile, the PI3K/AKT pathway was also involved in regulating the anti-inflammation effect. These findings define for the first time that the gastroprotective effects of KFX against gastric ulcer can be attributed to its role in NF-κB inhibition.
本研究旨在评估康复新(KFX)(一种从美洲大蠊中分离出的中成药成分)对小鼠乙醇诱导型胃溃疡的胃保护作用,并阐明其潜在作用机制。结果显示,用酒精处理的小鼠出现明显的胃黏膜损伤,而用西咪替丁(阳性对照)和KFX处理可显著减轻损伤,同时氧化应激和凋亡指标降低。随后,我们进行了无标记定量蛋白质组学(LFQ)分析,发现NF-κB和PI3K/AKT信号通路参与了KFX的胃保护作用。此外,蛋白质免疫印迹分析显示,KFX处理可抑制TNF-α、IL-1β的表达,显著降低IκB的磷酸化水平,并抑制NF-κB p65的核转位,这表明KFX抑制了NF-κB通路的激活。同时,PI3K/AKT通路也参与调节抗炎作用。这些发现首次明确,KFX对胃溃疡的胃保护作用可归因于其对NF-κB的抑制作用。