title: Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats.
abstract: Madecassoside, a triterpenoid derivative isolated from Centella asiatica, exhibits anti-inflammatory and antioxidant activities. We investigated its neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24mg/kg, i.v.) was administered 1h after the start of reperfusion, and neurological deficit score and infarct volume were evaluated 24h later. Neuronal apoptosis was assessed by performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, and pathological brain damage was estimated by performing hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide dismutase activity, reduced glutathione levels, and nitric oxide levels were also determined. mRNA and protein expression of pro-inflammatory cytokines (Interleukin-1β/6, and tumor necrosis factor-α) were measured by real-time RT-PCR and ELISA, respectively; NF-κB p65 expression was determined by western blotting. Madecassoside significantly reduced brain infarct area, resolved neurological deficit, and ameliorated neuronal apoptosis. It also significantly reduced the levels of malondialdehyde and nitric oxide, and augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover, the levels of pro-inflammatory cytokines and NF-κB p65 significantly reduced after madecassoside treatment. These results indicate that madecassoside is neuroprotective and may be useful in reducing the damage caused by stroke.
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Yang
authors.affiliation: Department of Emergency, PLA General Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Wan-Hua
authors.initials: WH
authors.lastname: Li
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sui
authors.affiliation: Department of Respiration, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Nie
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Beijing Suliman Pharmaceutical Co., Ltd., Beijing, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Beijing Suliman Pharmaceutical Co., Ltd., Beijing, China.
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Institutes of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China. Electronic address: yonganw@126.com.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014315:Triterpenes / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014315:Triterpenes; C093443:madecassoside
keywords: Apoptosis; Cerebral ischemia reperfusion; Inflammatory; Madecassoside; NF-κB pathway; Oxidative stress