Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Zhou, Yun; Li, Huiqin; Lü, Lin; Fu, Deng-lei; Liu, Aiju; Li, Ji-huang; 鄭, 国慶

doi:10.1016/j.phymed.2013.12.005

Cited by 83 publications

(59 citation statements)

References 32 publications

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“…Recently, Rg1 was found to improve neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of AQP4 expression. 39) With the results of this study, we considered that Rg1 markedly reduced the brain water contents of MCAO mice, which might be related to the suppression of astrocytes apoptosis by Rg1. This preliminary study needs further research to confirm whether AQP4 is involved in astrocytes apoptosis and brain edema.…”

Section: Discussionmentioning

confidence: 77%

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Sun¹,

Lai²,

Huang³

et al. 2014

Biological & Pharmaceutical Bulletin

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Ginsenoside Rg1 (Rg1), one of the active ingredients in Panax ginseng, has been known to regulate many cellular processes. The purpose of this study was to investigate the protective effects of Rg1 on apoptosis in mouse cultured astrocytes in vitro and a mouse model of cerebral ischemia and reperfusion in vivo. The cell apoptosis was measured by fluorescence microplate reader and xCELLigence system and the Ca 2 overload was recorded by confocal microscopy. The mitochondrial membrane potential and reactive oxygen species (ROS) were determined by flow cytometry. BALB/c mice were subjected to transient middle cerebral artery occlusion (MCAO) and randomly divided into four groups: Sham (sham-operated 0.9% saline), MCAO (MCAO 0.9% saline), Rg1-L (MCAO Rg1 20 mg/kg) and Rg1-H (MCAO Rg1 40 mg/kg). Neurological deficit scores, brain water content and infarct volume were evaluated at 24 h after reperfusion. The results showed that Rg1 significantly attenuated H 2 O 2 -induced apoptosis in astrocytes. Rg1 efficiently inhibited intracellular Ca 2 overload, loss of mitochondrial membrane potential, and ROS production in astrocytes. In vivo study, it was also observed that Rg1 markedly reduced the neurological deficit scores, brain edema, and infarct volume in the model mice. These results suggest that Rg1 possesses significant neuroprotective effects, which might be related to the prevention of astrocytes from apoptosis.

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Section: Discussionmentioning

confidence: 77%

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Sun¹,

Lai²,

Huang³

et al. 2014

Biological & Pharmaceutical Bulletin

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“…10 and 11). NGR1 is an estrogen receptor agonist (Sun et al, 2013;Gui et al, 2014) that can regulate the Nuclear factor kB (NF-kB) (Zhong L et al, 2015) or autophagy (Lu et al, 2011;Zhou et al, 2014) via estrogen receptor under the pathologic circumstance. In neuronal ischemia, NGR1 action on ERa and ERb as an agonist to strengthen the role of ERa and ERb then attenuates the ER stress.…”

Section: Discussionmentioning

confidence: 99%

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

Wang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Notoginsenoside R1 (NGR1) is a phytoestrogen that is isolated from Panax notoginseng. It is used in China to treat many diseases, including hypoxic-ischemic encephalopathy (HIE), and it has been shown to target estrogen receptors. Endoplasmic reticulum (ER) stress plays an important role in the development of cell apoptosis during ischemia, and ER stress is known to be regulated by estrogen; however, the neuroprotective mechanisms of NGR1 in neonatal HIE is unclear. In this study, oxygenglucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL), followed by exposure to a hypoxic environment in 7-dayold postnatal Sprague-Dawley rats were used to mimic HIE episodes. Potential neuroprotective effects of NGR1 against neonatal HIE and its mechanisms were examined. After HIE conditions in vitro and in vivo, we administered NGR1 or the estrogen receptor inhibitor ICI-182780 and measured cell apoptosis, brain injury by MTT assay, TTC stain, and so forth. Expression of estrogen receptors a (ERa) and b (ERb), ER stressassociated proteins was detected by Western blot upon stimulation with HIE, NGR1, or ICI-182780. Results showed that after HIE, ER chaperone GRP78 was activated, ER stress-associated proapoptotic proteins (CHOP, PERK, ERO1-a, and IRE1a) were increased, caspase-12 was increased, and BCL-2 was decreased. The ER stress response and neuronal apoptosis were attenuated by NGR1 treatment. However, neuroprotective properties of NGR1 against HIE-induced apoptosis and ER stress were attenuated by ICI-182780. These results suggest that NGR1 may be an effective treatment of HIE by reducing ER stress-induced neuronal apoptosis and brain injury via estrogen receptors.

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“…However, previous studies demonstrated that Rg1 was poorly absorbed and eliminated quickly 5 and could not efficiently transport through the blood-brain barrier (BBB) to achieve the effective concentration in the brain tissues. 6 The BBB was formed by brain micro vascular endothelial cells with tight junction to protect the brain from being harmed by the substances of blood. [7][8][9] The BBB restricts various therapeutic agents to enter the CNS.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

Shen¹,

Zhao²,

Wang³

et al. 2017

IJN

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Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

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Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Cited by 83 publications

References 32 publications

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Cited by 83 publications

References 32 publications

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Protective Effects of Ginsenoside Rg1 on Astrocytes and Cerebral Ischemic-Reperfusion Mice

Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

Ginsenoside Rg1 nanoparticle penetrating the blood&ndash;brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction