Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 260, Issue -, Pages 75-83Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2016.10.021
Keywords
Kangfuxin; Gastroprotection; Oxidative stress; ER stress; Apoptosis
Funding
- Good Doctor Pharmaceutical Group [KJHX1505]
- Zhejiang Provincial Natural Science Funding [LY14H150008]
- National Natural Science Funding of China [81472165, 81372112, 81572227]
- Zhejiang Provincial Program of Medical and Health Science [2014KYA131]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
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Oxidative stress and ER stress play a role in the pathogenesis of gastric ulcer. Kangfuxin (KFX) has been used to treat gastric ulcer in patients. However, the underlying mechanisms of KFX action remain unclear. The current study was undertaken to evaluate the gastroprotective effects of KFX and to determine its potential mechanisms. Ethanol-induced gastric ulcer mouse model was employed. Ethanol pretreated mice were treated with low (0.02 g/kg) and high (0.05 g/kg) dose of KFX for 14 days. Cimetidine (0.8 g/kg) was used as positive control. Histological evaluation of the gastric mucosa revealed that mice treated with ethanol exhibited severe gastric mucosa] damage. Ethanol treatment increased plasma and gastric MDA level, decreased plasma and gastric SOD activity, and reduced gastric HO-1 and GCL-c mRNA levels. ER stress markers (CHOP, GRP78, and caspase 12) were up-regulated upon ethanol administration. Moreover, increased cell apoptosis and pro-apoptotic protein Bax and caspase 3 were observed in ethanol treated mice, while the anti-apoptotic protein Bcl 2 was inhibited. Finally, KFX treatment reversed ethanol-induced phenotypes and ameliorated gastric ulcer. Our results demonstrated that the gastroprotective effects of KFX against ethanol-induced gastric ulcer could be attributed to its anti oxidative stress, anti-ER stress and anti-apoptotic effects. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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