scholarly journals Comparative Evaluation of Korean White Ginseng and Red Ginseng Efficacies in a Mouse Model of Ischemia/Reperfusion-Induced Stroke

2020 ◽  
Author(s):  
Myungho Jin ◽  
Kyung-Min Kim ◽  
Chiyeon Lim ◽  
Suin Cho ◽  
Young Kyun Kim
Keyword(s):  
Ischemic Stroke ◽  
Mouse Model ◽  
Cerebral Infarction ◽  
Ischemia Reperfusion ◽  
Protein Quantification ◽  
Cortical Region ◽  
Red Ginseng ◽  
Neuroprotective Effects ◽  
Potent Effect ◽  
White Ginseng

Abstract Background: Stroke is a condition characterized by brain tissue damage owing to a decrease in the brain's oxygen supply due to blocked blood vessels, and 80% of all strokes are classified as cerebral infarction. Notably, the incidence rate tends to increase with increasing age. In this study, we compared the efficacy of white ginseng (WG) and red ginseng (RG) extracts (WGex and RGex, respectively) in an ischemic stroke mouse model and confirmed the underlying mechanisms of action.Methods: Mice were orally administered WGex or RGex 1 h before performing middle cerebral artery occlusion (MCAO) for 2 h; the size of the infarct area was measured 24 h after MCAO. The neurological deficit score was evaluated, the efficacy of the two drugs was compared, and the mechanism of action was confirmed using methods such as tissue staining and protein quantification.Results: In the MCAO-induced ischemic stroke mouse model, WGex and RGex showed neuroprotective effects in the cortical region, with RGex demonstrating a generally stronger efficacy than WGex. Furthermore, it was confirmed that ginsenoside Rg1, a representative indicator substance, was not involved in mediating the effects of WGex and RGex.Conclusion: WGex and RGex inhibited brain injury attributed to ischemia/reperfusion, with RGex revealing a more potent effect. At 1,000 mg/kg body weight, only RGex reduced cerebral infarction and edema, and both anti-inflammatory and anti-apoptotic pathways were involved in mediating these effects.

scholarly journals Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia–Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1719
Author(s):  
Cheng-Tien Wu ◽  
Man-Chih Chen ◽  
Shing-Hwa Liu ◽  
Ting-Hua Yang ◽  
Lin-Hwa Long ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Ischemic Stroke ◽  
Mouse Model ◽  
Acute Ischemic Stroke ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Neuroprotective Effects ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded as the neuroprotective agents in disease models. In this study, we aimed to investigate and compare the neuroprotective effects of ICA and ICT in a middle cerebral artery occlusion (MCAO) mouse model. Male ICR mice were pretreated with both ICA and ICT, which ameliorated body weight loss, neurological injury, infarct volume, and pathological change in acute ischemic stroke mice. Furthermore, administration of both ICA and ICT could also protect against neuronal cell apoptotic death, oxidative and nitrosative stress, lipid peroxidation, and extracellular matrix (ECM) accumulation in the brains. The neuroprotective effects of ICT are slightly better than that of ICA in acute cerebral ischemic stroke mice. These results suggest that pretreatment with both ICA and ICT improves the neuronal cell apoptosis and responses of oxidative/nitrosative stress and counteracts the ECM accumulation in the brains of acute cerebral ischemic stroke mice. Both ICA and ICT treatment may serve as a useful therapeutic strategy for acute ischemic stroke.

scholarly journals Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Hua Shi ◽  
Xi-Le Zhang ◽  
Peng-Jie Ying ◽  
Zi-Qian Wu ◽  
Le-Le Lin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Ischemia Reperfusion ◽  
Neurological Dysfunction ◽  
Astragaloside Iv ◽  
Neuroprotective Effects ◽  
Ischemic Time ◽  
Cerebral Ischemia Reperfusion ◽  
Severity Scores

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway.Methods: Sprague–Dawley rats (male, 250–280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions.Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05).Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.

scholarly journals Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Juhyun Song ◽  
Joohyun Park ◽  
Yumi Oh ◽  
Jong Eun Lee
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Infarct Size ◽  
Cell Survival ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Cerebral Infarct ◽  
Ros Scavenging ◽  
The Brain

Ischemic stroke interrupts the flow of blood to the brain and subsequently results in cerebral infarction and neuronal cell death, leading to severe pathophysiology. Glutathione (GSH) is an antioxidant with cellular protective functions, including reactive oxygen species (ROS) scavenging in the brain. In addition, GSH is involved in various cellular survival pathways in response to oxidative stress. In the present study, we examined whether GSH reduces cerebral infarct size after middle cerebral artery occlusionin vivoand the signaling mechanisms involved in the promotion of cell survival after GSH treatment under ischemia/reperfusion conditionsin vitro. To determine whether GSH reduces the extent of cerebral infarction, cell death after ischemia, and reperfusion injury, we measured infarct size in ischemic brain tissue and the expression of claudin-5 associated with brain infarct formation. We also examined activation of the PI3K/Akt pathway, inactivation of FOXO3, and expression of Bcl2 to assess the role of GSH in promoting cell survival in response to ischemic injury. Based on our results, we suggest that GSH might improve the pathogenesis of ischemic stroke by attenuating cerebral infarction and cell death.

The effect of cyclosporin a on ischemia-reperfusion damage in a mouse model of ischemic stroke

2020 ◽  
Vol 42 (9) ◽  
pp. 721-729 ◽  
Author(s):  
Huajiang Deng ◽  
Shuang Zhang ◽  
Hongfei Ge ◽  
Liang Liu ◽  
Luotong Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Mouse Model ◽  
Cyclosporin A ◽  
Ischemia Reperfusion ◽  
Reperfusion Damage

Pharmacological connection of Histamine-1 (H1) Receptor Mediated Neuroprotective mechanism of Ischemic preconditioning in rat

2021 ◽  
pp. 2717-2722
Author(s):  
Prabhat Singh ◽  
Bhupesh Sharma
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Cerebral Stroke ◽  
H1 Receptor ◽  
Neuroprotective Effects ◽  
Motor Incoordination ◽  
Nitrite Nitrate

Cerebral ischemia and ischemia-reperfusion is an essential contributor to acute cerebral stroke. Ischemic preconditioning (IPC) has been proven to provide neuroprotection in ischemia-reperfusion injury in rats, but their mechanism behind neuroprotection in cerebral stroke are still unclear. Central histaminergic pathway has crucial role in the pathogenesis of cerebral stroke, but their neuroprotective role in IPC is still unidentified. This research explores the role of histamine-1 receptor in IPC induced neuroprotection against ischemia-reperfusion induced cerebral injury. Rat were subjected to 17 min of global cerebral ischemia (GCI) by occluding both carotid arteries followed by reperfusion for 24 h, to produce ischemia-reperfusion induced cerebral injury. TTC staining was used to measure cerebral infarct size. Morris water maze test was used to assess memory. Inclined beam-walk, hanging wire, lateral push and rota-rod tests were used to assess degree of motor incoordination. Brain acetylcholinesterase activity, nitrite/nitrate, glutathione, TBARS and MPO levels were also examined. GCI has produced a significant increase in cerebral infarction, brain nitrite/nitrate, MPO, TBARS and AChE activity along with a reduction in glutathione content. Impairment of memory and motor coordination were also noted in GCI induced rat. IPC was employed that consist of 3 preceding episodes of ischemia (1 min) and reperfusion (1 min) both immediately before GCI significantly decreased cerebral infarction, motor incoordination, memory impairment and biochemical impairment. Pretreatment with L-histidine mimicked the neuroprotective effects of IPC. L-histidine induced neuroprotection were significantly abolished by chlorpheniramine, a H1 receptor antagonist. We conclude that neuroprotective effects of IPC, probably occurs through the central histaminergic pathway, and histamine-1 receptor could be a new target behind the neuroprotective mechanism of IPC.

scholarly journals Neuronal GPR30 Participates in Genistein-Mediated Neuroprotection in Ischemic Stroke by Inhibiting NLRP3 Inflammasome Activation in Ovariectomized Female Mice

2021 ◽  
Author(s):  
Shiquan Wang ◽  
Zhen Zhang ◽  
Jin Wang ◽  
Lina Ma ◽  
Jianshuai Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nlrp3 Inflammasome Activation

Abstract Estrogen replacement therapy (ERT) is potentially beneficial for the prevention and treatment of postmenopausal cerebral ischemia but inevitably increases the risk of cerebral hemorrhage and breast cancer when used for a long period of time. Genistein, a natural phytoestrogen, has been reported to contribute to the recovery of postmenopausal ischemic stroke with reduced risks. However, the underlying mechanism of genistein-mediated neuroprotection remains unclear. We reported that genistein exerted significant neuroprotective effects by enhancing the expression of neuronal G protein-coupled receptor 30 (GPR30) in the ischemic penumbra after cerebral reperfusion in ovariectomized (OVX) mice, and this effect was achieved through GPR30-mediated inhibition of nod-like receptor protein 3 (NLRP3) inflammasome activation. In addition, we found that Peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) was the pivotal molecule that participated in GPR30-mediated inhibition of NLRP3 inflammasome activation in OVX mice after ischemia/reperfusion (I/R) injury. Our data suggest that the neuronal GPR30/PGC-1α pathway plays an important role in genistein-mediated neuroprotection against I/R injury in OVX mice.

scholarly journals Danggui-Shaoyao-San (DSS) Ameliorates Cerebral Ischemia-Reperfusion Injury via Activating SIRT1 Signaling and Inhibiting NADPH Oxidases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunxia Luo ◽  
Hansen Chen ◽  
Bun Tsoi ◽  
Qi Wang ◽  
Jiangang Shen
Keyword(s):  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Aqueous Extract ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Ethanol Extract ◽  
Dependent Manner ◽  
Neuroprotective Effects

Danggui-Shayao-San (DSS) is a famous Traditional Chinese Medicine formula that used for treating pain disorders and maintaining neurological health. Recent studies indicate that DSS has neuroprotective effects against ischemic brain damage but its underlining mechanisms remain unclear. Herein, we investigated the neuroprotective mechanisms of DSS for treating ischemic stroke. Adult male Sprague-Dawley (S.D.) rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Both ethanol extract and aqueous extract of DSS (12 g/kg) were orally administrated into the rats at 30 min prior to MCAO ischemic onset. We found that 1) ethanol extract of DSS, instead of aqueous extract, reduced infarct sizes and improved neurological deficit scores in the post-ischemic stroke rats; 2) Ethanol extract of DSS down-regulated the expression of the cleaved-caspase 3 and Bax, up-regulated bcl-2 and attenuated apoptotic cell death in the ischemic brains; 3) Ethanol extract of DSS decreased the production of superoxide and peroxynitrite; 4) Ethanol extract of DSS significantly down-regulated the expression of p67phox but has no effect on p47phox and iNOS statistically. 5) Ethanol extract of DSS significantly up-regulated the expression of SIRT1 in the cortex and striatum of the post-ischemic brains; 6) Co-treatment of EX527, a SIRT1 inhibitor, abolished the DSS’s neuroprotective effects. Taken together, DSS could attenuate oxidative/nitrosative stress and inhibit neuronal apoptosis against cerebral ischemic-reperfusion injury via SIRT1-dependent manner.

scholarly journals Effects of Alpha-Mangostin Encapsulated in Nanostructured Lipid Carriers in Mice with Cerebral Ischemia Reperfusion Injury

2021 ◽  
Vol 50 (7) ◽  
pp. 2007-2015
Author(s):  
Romgase Sakamula ◽  
Teerapong Yata ◽  
Wachiryah Thong-asa
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nanostructured Lipid Carriers ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia reperfusion injury (CIRI) is a phenomenon in which the cerebral blood supply is restored after a period of ischemia, resulting in irreversible damage to brain tissue. Oxidative stress plays a crucial role in the development of CIRI, therefore, targeting oxidative stress might be an effective strategy for CIRI prevention and treatment. Many therapeutic substances possess antioxidant and protective properties against neurodegenerative disorders but lack of in vivo application due to their solubility, and bioavailability. We investigated the effects of alpha-mangostin (αM) encapsulated in nanostructured lipid carriers (αM-NLC) on CIRI in mice. Forty male ICR mice were randomly divided into four groups: Sham, ischemia reperfusion (IR), ischemia reperfusion with 25 mg/kg of αM (IR+αM), and ischemia reperfusion with 25 mg/kg of αM-NLC (IR+αM-NLC). After 6 days of oral administrations, IR was delivered using 30 min of bilateral common carotid artery occlusion, followed by 45 min of reperfusion. Cerebral infarction volume, hippocampal neuronal and corpus callosum (CC) white matter damage, malondialdehyde (MDA) level, and catalase (CAT) activity were evaluated. Our results indicated that αM and αM-NLC prevent lipid peroxidation as well as hippocampal CA1, CA3, and CC damage (p<0.05). Only αM-NLC prevented cerebral infarction and enhanced CAT activity (p<0.05). We therefore conclude that αM and αM-NLC have neuroprotective effects against CIRI, and NLC increases therapeutic efficacy of αM against CIRI.

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