title: Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats.
abstract: We previously found that ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, attenuates neuronal oxidative damage in vitro induced by hydrogen peroxide and oxygen-glucose deprivation. In this study, we sought to investigate the potential protective effects and associated mechanisms of Rd in a rat model of focal cerebral ischemia. Rats administered with Rd (0.1-200mg/kg) or vehicle was subjected to transient middle cerebral artery occlusion. Rd at the dose of 10-50mg/kg significantly reduced the infarct volume and improved the long-term neurological outcome up to 6 weeks after ischemia. To evaluate the underlying mechanisms, in vivo free radical generation was monitored using microdialysis, oxidative DNA damage was identified by 8-hydroxy-deoxyguanosine immunostaining, oxidative protein damage was identified by the assessment of protein carbonyl and advanced glycosylation end products, and lipid peroxidation was estimated by determining the malondialdehyde and 4-hydroxynonenal formations. Microdialysis results displayed a prominent inhibitory effect of Rd on the hydroxy radical formation trapped as 2,3- and 2,5-DHBA. Early accumulations of DNA, protein and lipid peroxidation products were also suppressed by Rd treatment. Although Rd partly preserved endogenous antioxidant activities in the ischemic penumbra, in sham rats without stroke, endogenous antioxidant activities were not affected by Rd. Furthermore, we assayed sequential inflammatory response in a later phase after ischemia. Rd significantly eliminated inflammatory injury as indicated by the suppression of microglial activation, inducible nitric oxide synthase and cyclooxygenase-2 expression. Collectively, these findings demonstrated that Rd exerts neuroprotection in transient focal ischemia, which may involve early free radicals scavenging pathway and a late anti-inflammatory effect.
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. yeruid@gmail.com
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Yang
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Kong
authors.forename: Junliang
authors.initials: J
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Juanfang
authors.initials: J
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D005894:Panax / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D036145:Ginsenosides; D018696:Neuroprotective Agents; C049863:ginsenoside Rd