title: Involvement of Connexin40 in the Protective Effects of Ginsenoside Rb1 Against Traumatic Brain Injury.
abstract: Ginsenosides are the major active components of ginseng, which have been proven to be effective in therapies for neurodegenerative diseases. Ginsenoside Rb1 (GS-Rb1) is the most abundant among all the identified ginsenosides and has been shown to exert neuroprotective effects, although the underlying molecular mechanisms remain unclear. Connexins are a family of transmembrane proteins that form gap junctions, which are important for diffusion of cytosolic factors such as ions and second messenger signaling molecules. Previous studies have shown that a subset of connexin proteins is involved in neuroprotection. We investigated the protective effects of GS-Rb1 against traumatic brain injury (TBI) and the potential mechanism using TBI mouse model. We discovered that TBI-induced brain injury and up-regulation of connexin40 (Cx40) protein expression as early as 6 h post-TBI, which was reversed by administration of GS-Rb1. In addition, we found that the protective effects of GS-Rb1 are dose and time dependent and are partially mediated through phosphorylation of ERK1/2 signaling pathway, as evidenced by the abolishment of GS-Rb1-mediated elevation of p-ERK1/2 expression and inhibition of Cx40 expressions when ERK inhibitor U0126 was used. Our study provides evidence that Cx40 is implicated in TBI-induced brain injuries, and GS-Rb1 exerts neuroprotective activity against TBI involving down-regulation of Cx40 expression.
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. wstong3@sina.com.
authors.forename: Wusong
authors.initials: W
authors.lastname: Tong
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D036145:Ginsenosides; D018696:Neuroprotective Agents; D000097003:Gap Junction alpha-5 Protein; C442759:ginsenoside Rb1
keywords: Connexin40; Ginsenoside Rb1; Neuroprotective activity; TBI