FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Ameliorates DSS-Induced Colitis Against Oxidative Stress by Activating Nrf2/HO-1 Pathway

Mei, Yu1,2; Wang, Zihao3,4; Zhang, Yifan1,2; Wan, Ting1,2; Xue, Jincheng1,2; He, Wei1,2; Luo, Yi1,2; Xu, Yijun1,2; Bai, Xue5; Wang, Qi1,2; Huang, Yujie1,2

2020-01-08

10.3389/fimmu.2019.02969

Frontiers in Immunology   影响因子和分区

1664-3224

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder of gastro-intestinal tract, lacking effective drug targets and medications. Caffeic acid phenethyl ester (CAPE), a phenolic constituent derived from propolis, has been reported to be a potential therapeutic agent for IBD with low water solubility and poor bioavailability. In this study, we synthesized a new CAPE derivative (FA-97) and aimed to investigate the effect of FA-97 on DSS-induced colitis. Here, we found that FA-97 attenuated body weight loss, colon length shortening and colonic pathological damage in colitis mice, as well as inhibited inflammatory cell infiltration and expression of pro-inflammatory cytokines in colons. In addition, FA-97 reduced ROS production and MDA generation, while total antioxidant capacity both in DSS-induced colitis mice and LPS-stimulated primary BMDMs and RAW 264.7 cells were enhanced. Mechanically, FA-97 activated Nrf2 followed by increased HO-1 and NQO-1 and down-regulated nuclear levels of p65 and c-Jun, to suppress DSS-induced colonic oxidative stress. Moreover, FA-97 decreased pro-inflammatory cytokine expression and increased the antioxidant defenses in RAW 264.7 via Nrf2 activation. In general, this study reveals that FA-97 activates Nrf2/HO-1 pathway to eventually alleviate DSS-induced colitis against oxidative stress, which has potential activity and may serve as a candidate for IBD therapy.

inflammatory bowel disease oxidative stress nuclear factor erythroid 2-related factor (Nrf2) reactive oxygen species (ROS) caffeic acid phenethyl ester (CAPE)

SCI

英语

其他

Guangzhou Science Technology and Innovation Commission Technology Research Projects[201805010005] ; Guangzhou Science Technology and Innovation Commission Technology Research Projects[A1-AFD018181Z3926]

Immunology

Immunology

WOS:000512373800001

FRONTIERS MEDIA SA

Web of Science

1.Guangzhou Univ Chinese Med, Sci & Technol Innovat Ctr, Guangzhou, Guangdong, Peoples R China
2.Guangzhou Univ Chinese Med, Inst Clin Pharmacol, Guangzhou, Guangdong, Peoples R China
3.Hong Kong Baptist Univ, Ctr Clin Res Chinese Med, Sch Chinese Med, Inst Brain & Gut Axis IBAG,Kowloon Tong, Hong Kong, Peoples R China
4.Southern Univ Sci & Technol, Dept Chem, Shenzhen, Guangdong, Peoples R China
5.Southwestern Med Univ, Affiliated Chinese Med Hosp, Quzhou, Peoples R China

Mei, Yu,Wang, Zihao,Zhang, Yifan,et al. FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Ameliorates DSS-Induced Colitis Against Oxidative Stress by Activating Nrf2/HO-1 Pathway[J]. Frontiers in Immunology,2020,10.

Mei, Yu.,Wang, Zihao.,Zhang, Yifan.,Wan, Ting.,Xue, Jincheng.,...&Huang, Yujie.(2020).FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Ameliorates DSS-Induced Colitis Against Oxidative Stress by Activating Nrf2/HO-1 Pathway.Frontiers in Immunology,10.

Mei, Yu,et al."FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Ameliorates DSS-Induced Colitis Against Oxidative Stress by Activating Nrf2/HO-1 Pathway".Frontiers in Immunology 10(2020).