title: Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia.
abstract: The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor-interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-κB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Zhanqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Lingpeng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, 210009, China. machuanhua25@126.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. yantianhuabest@126.com.|Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, 210009, China. yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D005960:Glucosides; D016328:NF-kappa B; D056971:Nuclear Receptor Co-Repressor 1; D010636:Phenols; D051028:bcl-2-Associated X Protein; C009172:rhodioloside
keywords: Cerebral ischemia; Inflammation; RIP140; Salidroside