title: Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.
abstract: Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury.
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Gong
authors.affiliation: School of Life Science and Biotechnology, China Pharmaceutical University, 24 Tongjia Street, Nanjing 210009, PR China.
authors.forename: Fumou
authors.initials: F
authors.lastname: Sun
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Fugang
authors.initials: F
authors.lastname: Duan
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
authors.forename: Hansen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China. Electronic address: qisuhua9999@163.com.
authors.forename: Suhua
authors.initials: S
authors.lastname: Qi
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. Electronic address: shenjg@hkucc.hku.hk.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D029777:Momordica charantia / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D011134:Polysaccharides / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D005609:Free Radicals; D018696:Neuroprotective Agents; D011134:Polysaccharides; D048057:Mitogen-Activated Protein Kinase 10
keywords: Antioxidants; Cerebral ischemia-reperfusion injury; JNK signaling pathway; Momordica charantia polysaccharide