Dataset Information

Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window.

ABSTRACT: Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has been demonstrated to protect against ischemic cerebral damage in vitro and in vivo. In this study, we aimed to further define the preclinical characteristics of Rd. We show that Rd passes the intact blood-brain barrier and exerts protection in both transient and permanent middle cerebral artery occlusion (MCAO) in rats. In the dose-response study, Rd (10-50 mg/Kg) significantly reduced the infarct volume on postoperative days (PODs) 1, 3, and 7. This protection was associated with an improved neurological outcome for as many as 6 weeks after transient MCAO, as assessed by modified neurological severity score, modified sticky-tape test, and corner test. For comparison, Rd was significantly more effective than edaravone and slightly more effective than N-tert-butyl-alpha-phenylnitrone (PBN). In the therapeutic window study, Rd exhibited remarkable neuroprotection, even when administered for as many as 4 h after the recirculation of transient MCAO or after the onset of permanent MCAO. Furthermore, in female rats or 16-month-old male rats, the salutary effects of Rd were also observed. These findings suggest Rd is a promising neuroprotectant and provide support for future clinical studies to confirm whether Rd is beneficial in ischemic stroke.

SUBMITTER: Ye R

PROVIDER: S-EPMC3250281 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window.

Ye Ruidong R Kong Xiangwei X Yang Qianzi Q Zhang Yunxia Y Han Junliang J Li Ping P Xiong Lize L Zhao Gang G

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20110701 3

Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has been demonstrated to protect against ischemic cerebral damage in vitro and in vivo. In this study, we aimed to further define the preclinical characteristics of Rd. We show that Rd passes the intact blood-brain barrier and exerts protection in both transient and permanent middle cerebral artery occlusion (MCAO) in rats. In the dose-response study, Rd (10-50 mg/Kg) significantly reduced the infarct volume on postoperati ...[more]

PMID: 21647765

Similar Datasets

Project description:Ischemic stroke, the most common type of stroke, can lead to a long-term disability with the limitation of effective therapeutic approaches. Ginsenoside-Rd (G-Rd) has been found as a neuroprotective agent. In order to investigate and discuss the neuroprotective function and underlying mechanism of G-Rd in experimental animal models following cerebral ischemic/reperfusion (I/R) injury, PubMed, Embase, SinoMed, and China National Knowledge Infrastructure were searched from their inception dates to May 2022, with no language restriction. Studies that G-Rd was used to treat cerebral I/R damage in vivo were selected. A total of 18 articles were included in this paper, and it was showed that after cerebral I/R damage, G-Rd administration could significantly attenuate infarct volume (19 studies, SMD = −1.75 [−2.21 to − 1.30], P < 0.00001). Subgroup analysis concluded that G-Rd at the moderate doses of >10- <50 mg/kg reduced the infarct volume to the greatest extent, and increasing the dose beyond 50 mg/kg did not produce better results. The neuroprotective effect of G-Rd was not affected by other factors, such as the animal species, the order of administration, and the ischemia time. In comparison with the control group, G-Rd administration could improve neurological recovery (lower score means better recovery: 14 studies, SMD = −1.50 [−2.00 to − 1.00], P < 0.00001; higher score means better recovery: 8 studies, SMD = 1.57 [0.93 to 2.21], P < 0.00001). In addition, this review suggested that G-Rd in vivo can antagonize the reduced oxidative stress, regulate Ca2+, and inhibit inflammatory, resistance to apoptosis, and antipyroptosis on cerebral I/R damage. Collectively, G-Rd is a promising natural neuroprotective agent on cerebral I/R injury with unique advantages and a clear mechanism of action. More clinical randomized, blind-controlled trials are also needed to confirm the neuroprotective effect of G-Rd on cerebral I/R injury.

Project description:Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague-Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg(-1), i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end-labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury-induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in part due to the reduction of peroxynitrite and apoptosis.

Dataset Information

Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window.

Publications

Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets