Gastroprotective effects of Kangfuxin-against ethanol-induced gastric ulcer via attenuating oxidative stress and ER stress in mice

Pianpian Chen; Yongmei Shen; Hongxue Shi; Xiuying Ma; Beibei Lin; Tong Xiao; Fenzan Wu; Jingjing Zhu; Zhengmao Li; Jian Xiao; Xiaokun Li; Hongyu Zhang; Funeng Geng

doi:10.1016/j.cbi.2016.10.021

Gastroprotective effects of Kangfuxin-against ethanol-induced gastric ulcer via attenuating oxidative stress and ER stress in mice

Chem Biol Interact. 2016 Oct 28:S0009-2797(16)30509-9. doi: 10.1016/j.cbi.2016.10.021. Online ahead of print.

Authors

Pianpian Chen¹, Yongmei Shen², Hongxue Shi¹, Xiuying Ma², Beibei Lin¹, Tong Xiao¹, Fenzan Wu³, Jingjing Zhu¹, Zhengmao Li¹, Jian Xiao¹, Xiaokun Li¹, Hongyu Zhang⁴, Funeng Geng⁵

Affiliations

¹ School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
² Sichuan Key Laboratory of Medical American Cockroach, Chengdu, 610000, China.
³ Science and Education Division, Cixi People's Hospital, Wenzhou Medical University, Ningbo, 315300, China.
⁴ School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China. Electronic address: st_hyz@126.com.
⁵ Sichuan Key Laboratory of Medical American Cockroach, Chengdu, 610000, China. Electronic address: haoyishenggfn@126.com.

PMID: 27983966
DOI: 10.1016/j.cbi.2016.10.021

Abstract

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 mucosal 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.

Keywords: Apoptosis; ER stress; Gastroprotection; Kangfuxin; Oxidative stress.