Efficacy and safety of ginsenoside‐Rd for acute ischaemic stroke: a randomized, double‐blind, placebo‐controlled, phase II multicenter trial

Liu, X.; Xia, Jielai; Wang, L.; Song, Yilun; Yang, Ji-Young; Yan, Yongmin; Ren, Hua; Zhao, Gang

doi:10.1111/j.1468-1331.2009.02534.x

Cited by 81 publications

(50 citation statements)

References 29 publications

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“…Our previous in vitro and in vivo studies have demonstrated that GSRd has neuroprotective effects on injured neurons (Ye et al 2008;Liu et al 2009;Ye et al 2009;Ye et al 2011a;Ye et al 2011b). In the present study, we showed that GSRd attenuated glutamate-and NMDA-induced excitotoxic injury of cultured rat hippocampal neurons by inhibiting Ca 2?…”

Section: Discussionmentioning

confidence: 96%

“…In our randomized, double-blind, placebo-controlled, phase II multicenter trial, we found that GSRd shows efficacy and safety for the treatment of acute ischemic stroke (Liu et al 2009). Moreover, we found that GSRd can attenuate the cytotoxicity of PC12 cells induced by hydrogen peroxide, protect against the injury of cultured hippocampal neurons induced by oxygen-glucose deprivation (Ye et al 2008;Ye et al 2009), and attenuate apoptosis and inflammation after transient focal ischemia (Ye et al 2011a;Ye et al 2011b).…”

Section: Introductionmentioning

confidence: 96%

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Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca2+ Influx

Zhang

Shi

et al. 2011

Cell Mol Neurobiol

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Our previous studies have demonstrated that ginsenoside Rd (GSRd), one of the principal ingredients of Pana notoginseng, has neuroprotective effects against ischemic stroke. However, the possible mechanism(s) underlying the neuroprotection of GSRd is/are still largely unknown. In this study, we treated glutamate-injured cultured rat hippocampal neurons with different concentrations of GSRd, and then examined the changes in neuronal apoptosis and intracellular free Ca(2+) concentration. Our MTT assay showed that GSRd significantly increased the survival of neurons injured by glutamate in a dose-dependent manner. Consistently, TUNEL and Caspase-3 staining showed that GSRd attenuated glutamate-induced cell death. Furthermore, calcium imaging assay revealed that GSRd significantly attenuated the glutamate-induced increase of intracellular free Ca(2+) and also inhibited NMDA-triggered Ca(2+) influx. Thus, the present study demonstrates that GSRd protects the cultured hippocampal neurons against glutamate-induced excitotoxicity, and that this neuroprotective effect may result from the inhibitory effects of GSRd on Ca(2+) influx.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca2+ Influx

Zhang

Shi

et al. 2011

Cell Mol Neurobiol

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“…Various research studies as well as clinical trials have been conducted to examine the effect of various antiinflammatory treatments after ischemic stroke (Table 2). While two of these studies report better outcomes with their antiinflammatory treatment, 91,92 the remaining studies report worse outcomes, 93,94 no difference between treatment and placebo, [95][96][97][98] or were simply safety studies [99][100][101] with all of them failing to make it beyond clinical phase trials. Importantly, some of these studies were underpowered to detect a meaningful clinical effect.…”

Section: Antiinflammatory Treatment Strategiesmentioning

confidence: 99%

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Tobin

Bonds

Minshall

et al. 2014

J Cereb Blood Flow Metab

298

236

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This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.

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“…Currently Rd is being developed to treat patients with acute ischemic stroke. Several studies have been reported demonstrating the pharmacokinetics [35], safety [36], and preliminary efficacy [37] of Rd in human subjects. More recently, a phase III multicenter clinical trial of Rd showed a benefit in terms of the prespecified primary endpoint, the distribution of disability as measured by the modified Rankin score at 90 days after stroke onset.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rd in Experimental Stroke: Superior Neuroprotective Efficacy with a Wide Therapeutic Window

Kong

Yang

et al. 2011

Neurotherapeutics

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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 Ntert-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.

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Efficacy and safety of ginsenoside‐Rd for acute ischaemic stroke: a randomized, double‐blind, placebo‐controlled, phase II multicenter trial

Abstract: Ginsenoside-Rd may be of some benefit in acute ischaemic stroke.

Cited by 81 publications

References 29 publications

Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca2+ Influx

Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca2+ Influx

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Ginsenoside Rd in Experimental Stroke: Superior Neuroprotective Efficacy with a Wide Therapeutic Window

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