ginsenoside-rd and Reperfusion-Injury

Paraplegia may develop as a result of spinal cord ischemia-reperfusion injury in patients who underwent thoracoabdominal aortic surgery. The objective of this research is to determine the neuroprotective effects of ginsenoside Rd pretreatment in a rat model of spinal cord ischemia-reperfusion injury.. Sprague-Dawley rats (n=36) were randomly assigned to three groups. The sham (n=12) and control (n=12) groups received normal saline orally. The Rd group (n=12) received ginsenoside Rd (100 mg/kg) orally 48 hours before the induction of spinal cord ischemia. Spinal cord ischemia was induced by aortic occlusion using a Fogarty balloon catheter in the Rd and control groups. A neurological assessment according to the motor deficit index and a histological evaluation of the spinal cord were performed. To evaluate the antioxidant activity of ginsenoside Rd, malondialdehyde levels and superoxide dismutase activity were determined. Further, the tissue levels of tumor necrosis factor-alpha and interleukin-1 beta were measured.. The Rd group showed significantly lower motor deficit index scores than did the control group throughout the entire experimental period (P<0.001). The Rd group demonstrated significantly greater numbers of normal motor neurons than did the control group (P=0.039). The Rd group exhibited decreased malondialdehyde levels (P<0.001) and increased superoxide dismutase activity (P=0.029) compared to the control group. Tumor necrosis factor-alpha and interleukin-1 beta tissue levels were significantly decreased in the Rd group (P<0.001).. Ginsenoside Rd pretreatment may be a promising treatment to prevent ischemia-reperfusion injury in patients who undergo thoracoabdominal aortic surgery.

Topics: Animals; Disease Models, Animal; Interleukin-1beta; Malondialdehyde; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spinal Cord Ischemia; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Pyroptosis mediated by nucleotide-binding oligomerization domain (NOD)-like receptor 3 (NLRP3) inflammasome is implicated in cerebral ischemia/reperfusion (I/R) injury. Ginsenoside Rd (Rd), a monomer component of Panax ginseng and Panax notoginseng, is reported to confer neuroprotection in brain injury models. However, the role of pyroptosis in Rd-mediated neuroprotection following cerebral I/R has not been investigated. We aimed to confirm the neuroprotective function and underlying mechanisms of Rd on pyroptosis after cerebral I/R using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in male C57BL/6 mice, and oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons. MicroRNA-139-5p (miR-139-5p) downregulation, forkhead box transcription factor O1 (FOXO1) and Kelch-like ECH-associated protein 1 (Keap1) upregulation, nuclear factor erythroid-2 related factor 2 (Nrf2) antioxidant pathway inactivation, reactive oxygen species (ROS)-driven thioredoxin-interacting protein (TXNIP) over-expression, and NLRP3 inflammasome activation-induced pyroptosis were observed in ischemic cortical tissues and primary neurons under MCAO/R and OGD/R induction. More importantly, Rd upregulated miR-139-5p to inhibit FoxO1 which regulates Keap1 transcriptional activity, and subsequently activates the Nrf2 antioxidant pathway, resulting in attenuation of ROS/TXNIP/NLRP3 inflammasome axis-driven pyroptosis in these animal and cell models. In summary, an anti-pyroptotic effect via the miR-139-5p/FoxO1/Keap1/Nrf2 axis may be the mechanism by which Rd attenuates ischemic stroke.

Topics: Animals; Brain Ischemia; Forkhead Box Protein O1; Ginsenosides; Kelch-Like ECH-Associated Protein 1; Male; Mice; Mice, Inbred C57BL; MicroRNAs; NF-E2-Related Factor 2; Reperfusion Injury; Signal Transduction

Ginsenoside Rd (GSRd) is one of the active ingredients in ginseng. Recent studies have shown that GSRd can protect against cerebral ischemia through several pathways, one of which is mediated by the N-methyl-D-aspartate receptor (NMDAR). In this study, we aimed to investigate the effects of GSRd on the phosphorylation of the NMDAR 2B subunit (NR2B subunit) in cerebral ischemia. Ischemia-reperfusion injury (IRI) models induced by transient middle cerebral artery occlusion (MCAO) and oxygen glucose deprivation (OGD) were used to mimic in vivo or in vitro injury during cerebral ischemia. The models were pretreated or post-treated with GSRd after MCAO or OGD. As a vehicle control, 1,3-propanediol was used. The expression levels of the NR2B subunit and the phosphorylated NR2B subunit were determined using western blotting. GSRd significantly improved the behavior score, infarct volume, and viability of the cultured neurons after ischemia. GSRd inhibited the hyperphosphorylation of NR2B subunit and decreased the expression levels of NR2B subunit in cell membrane but did not change their levels in the total proteins after IRI. GSRd protected Sprague-Dawley rats and cultured neurons from IRI via inhibiting the hyperphosphorylation of NR2B subunit and decreasing its expression levels in cell membrane.

Topics: Animals; Brain Ischemia; Cell Survival; Cells, Cultured; Gene Expression Regulation; Ginsenosides; Male; Neuroprotective Agents; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reperfusion Injury

To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI).. Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg(-1)·d(-1), ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg(-1)·d(-1), ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting.. Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg(-1)·d(-1)) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 μmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002.. Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.

Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Doublecortin Protein; Ginsenosides; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; MAP Kinase Signaling System; Neurogenesis; Panax; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Vascular Endothelial Growth Factor A