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 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.

HO-1 Signaling Activation by Pterostilbene Treatment Attenuates Mitochondrial Oxidative Damage Induced by Cerebral Ischemia Reperfusion Injury

“…The results clearly indicated that PTE treatment resulted in a wellpreserved MMP, mitochondria complex I activity, mitochondria complex IV activity, and mitochondrial cytochrome c expression and decreased cytosolic cytochrome c expression. Mitochondrial oxidative damage has been directly implicated in a variety of pathological situations, including cerebral IRI [36,37]. The occurrence of mitochondrial oxidative damage contributes to an increased loss of efficiency in mitochondrial function, which further improves mitochondrial oxidative damage and ultimately aggravates cerebral IRI.…”

“…As described previously [37], mitochondrial membrane potential (MMP) was determined using JC-1. Mitochondria samples (0.5 mg/mL, 1 mL) were incubated with 19 mL JC-1 staining buffer according to the manufacturer's instructions (Sigma-Aldrich, St. Louis, MO, USA).…”

“…As described previously [37], mitochondrial reactive oxygen species (ROS) production was measured using the indicator dichlorodihydrofluorescein diacetate (H2DCFDA, Invitrogen, Carlsbad, CA, USA) as described. Mitochondrial protein was incubated in a total volume of 200 μL respiration buffer including 5 mM pyruvate and 2.5 mM malate as substrate at 37°C for 15 min in the presence of 10 μM H2DCFDA, which was made fresh before each use.…”

Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway

“…Acta Pharmacologica Sinica npg permanent MCAO in rats [7] . However, although this traditional Chinese medicine has long been used to strengthen the body's resistance to pathogenic factors, the beneficial effects of ginsenosides on cerebral self-remodeling after ischemia have not been fully elucidated.…”

Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats

“…Recent studies on the mechanism of spinal cord injury suggest that free radicals affect the development of the spinal cord injury by enhancing partial ischemia-reperfusion injury (Sun et al, 2010;He et al, 2010;Wang et al, 2011). Edaravone is a radical scavenger (Uji et al, 2008;Hisano et al, 2009;Ye et al, 2011;Ono et al, 2011). The current study aimed to observe the effect of edaravone on the repair of rat spinal cord injury and to explore the potential of the combination of edaravone with neural stem cell (NSC) transplantation to treat spinal cord injury.…”