title: Neuroprotective effect of salvianolic acid B against cerebral ischemic injury in rats via the CD40/NF-κB pathway associated with suppression of platelets activation and neuroinflammation.
abstract: Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases. In the present study, a rat model of transient middle cerebral artery occlusion (tMCAO) was established to investigate the neuroprotective effects and mechanisms of SAB treatment against focal cerebral I/R insult. The results showed that SAB treatment (3mg/kg, 6mg/kg and 12mg/kg, i.p.) dose-dependently decreased I/R-induced neurological deficits at 24, 48, and 72h after reperfusion and decreased plasma-soluble P-selectin and soluble CD40 ligand as early as 6h after onset of I/R insult. At 24h after reperfusion, SAB treatment significantly reduced neuronal and DNA damage in the hippocampal CA1 region and decreased neural cell loss in the ischemic core. The I/R-induced pro-inflammatory mediator mRNA and protein overexpression in the penumbra cortex, including ICAM-1, IL-1β, IL-6, IL-8, and MCP-1, were significantly inhibited by SAB in a dose-dependent manner. Further studies suggested SAB treatment attenuated CD40 expression and NF-κB activation, which involved NF-κB/p65 phosphorylation and IκBα phosphorylation and degradation. In conclusion, our findings indicated that the neuroprotective effects of SAB post cerebral I/R injury are associated with the inhibition of both platelets activation and production of pro-inflammatory mediators and the downregulation of the CD40/NF-κB pathway.
authors.affiliation: Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin 300193, China. Electronic address: shixinxu1973@outlook.com.
authors.forename: Shixin
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin 300193, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Zhong
authors.affiliation: Tianjin University of Traditional Chinese Medicine, 312 An Shan Xi Road, Nan Kai District, Tianjin 300193, China.
authors.forename: Huining
authors.initials: H
authors.lastname: Ma
authors.affiliation: Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin 300193, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Tianjin University of Traditional Chinese Medicine, 312 An Shan Xi Road, Nan Kai District, Tianjin 300193, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin 300193, China.
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nan Kai District, Tianjin 300193, China. Electronic address: tjzhtcm@163.com.
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D002545:Brain Ischemia / Q000517:prevention & control* / Q000628:therapy*; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D019013:CD40 Antigens / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation; D018696:Neuroprotective Agents / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D053630:Depsides
chemical_list: D001572:Benzofurans; D019013:CD40 Antigens; D016328:NF-kappa B; D018696:Neuroprotective Agents; D051996:Transcription Factor RelA; C076944:salvianolic acid B; D053630:Depsides
keywords: Cerebral ischemia/reperfusion injury; Inflammation; Platelets activation; Salvianolic acid B