title: Protective effect of ginsenoside Rb1 on integrity of blood-brain barrier following cerebral ischemia.
abstract: Ginsenosides, the major bioactive compounds in ginseng root, have been found to have antioxidant, immunomodulatory, and anti-inflammatory activities. In the present study, we sought to investigate whether and how ginsenoside Rb1 (GS-Rb1), the most abundant ginsenoside, can protect blood-brain barrier (BBB) integrity following cerebral ischemia in middle cerebral artery occlusion (MCAO) animal model. ICR mice underwent MCAO and received GS-Rb1 by intraperitoneal injection at 3 h after reperfusion. We evaluated infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression at 48 h after MCAO. We further examined whether GS-Rb1 protected BBB integrity by suppressing post-ischemic inflammation-induced activity of matrix metalloproteinase-9 (MMP-9) and nicotinamide adenine dinucleotide phosphate oxidase (NOX). First, GS-Rb1 decreased infarction and improved neurological deficits in MCAO animals. In addition, GS-Rb1 reduced EB extravasation and brain edema and preserved expression of tight junction proteins in the ischemic brain. Moreover, GS-Rb1 inhibited expression of pro-inflammatory factors including nitric oxide synthase and IL-1β, but increased expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Consistently, GS-Rb1 attenuated ischemia-induced expression and activity of MMP9. Finally, GS-Rb1 reduced NOX-4 mRNA expression and NOX activity in ischemic brain. These results suggest that GS-Rb1 protects loss of BBB integrity in ischemic stroke by suppressing neuroinflammation induction of MMP-9 and NOX4-derived free radicals, and indicate its potential for treating brain injuries, such as ischemia and stroke.
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yang
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zeng
authors.affiliation: The People's Hospital of Pu Dong New Area, 490 South Chuanhuan Road, Chuansha New Town, Shanghai, 201299, People's Republic of China. wusongtong@163.com.
authors.forename: Wusong
authors.initials: W
authors.lastname: Tong
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D036145:Ginsenosides; D018696:Neuroprotective Agents; C442759:ginsenoside Rb1
keywords: Blood–brain barrier; Cerebral artery occlusion; Cerebral ischemia; Ginsenoside Rb1