scholarly journals Hydroxysafflor Yellow A and Anhydrosafflor Yellow B Protect Against Cerebral Ischemia/Reperfusion Injury by Attenuating Oxidative Stress and Apoptosis via the Silent Information Regulator 1 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yijia Fangma ◽  
Huifen Zhou ◽  
Chongyu Shao ◽  
Li Yu ◽  
Jiehong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Water Soluble ◽  
Hydroxysafflor Yellow A ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Silent Information Regulator 1

Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) are the main water-soluble compounds in Carthamus tinctorius L. However, studies on the effect of AHSYB on cerebral ischemia/reperfusion (I/R) injury and the therapeutic effect of HSYA by regulating silent information regulator 1 (SIRT1) pathway remain obscure. In this study, we investigated whether the neuroprotective effects of HSYA and AHSYB on oxygen-glucose deprivation/reoxygenation in primary-cultured hippocampal neuronal cells and the middle cerebral artery occlusion and reperfusion model in rats are associated with the regulation of the SIRT1 pathway. In vitro, HSYA and AHSYB increased cell viability, depressed oxidation properties, and reduced neuronal cell apoptosis. In vivo results showed that HSYA and AHSYB effectively reduced infarct volume, improved neurological function, suppressed apoptosis, and decreased the oxidative stress reaction. Besides, RT-PCR and Western blot analysis showed that HSYA and AHSYB increased the mRNA and protein expressions of the main factors in the SIRT1 pathway, including SIRT1, forkhead box O (FOXO) 1, and peroxisome proliferator–activated receptor coactivator 1α (PGC1α), decreased the expression of Bax, and increased the expression of Bcl-2. The results from immunohistochemistry also showed that the expressions of SIRT1, FOXO1, and PGC1α were increased after treatment with HSYA and AHSYB. Furthermore, the neuroprotective effects of HSYA and AHSYB were abolished by EX527 (SIRT1–specific inhibitor). These results indicated that HSYA and AHSYB should be developed into potential drugs for treating cerebral I/R injury via the SIRT1 pathway. Although HSYA and AHSYB have different chemical structures, both of them exert similar neuroprotective properties against I/R injury in vitro and in vivo, which means that AHSYB is also a non-negligible component in safflower.

scholarly journals Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Bo Zhao ◽  
Quan Yuan ◽  
Jia-bao Hou ◽  
Zhong-yuan Xia ◽  
Li-ying Zhan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
High Glucose ◽  
Ischemia Reperfusion ◽  
Pathological Process ◽  
Diabetic Mice ◽  
Diabetic State ◽  
Cerebral Ischemia Reperfusion

Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.

scholarly journals Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Jing Zeng ◽  
Long Zhu ◽  
Jing Liu ◽  
Tao Zhu ◽  
Zhaohui Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Neuroprotective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury

Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

scholarly journals Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yong Gu ◽  
Xi Chen ◽  
Shuping Fu ◽  
Wenlan Liu ◽  
Qi Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuroprotective Effects ◽  
Astragali Radix ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Isoflavones are major neuroprotective components of a medicinal herb Astragali Radix, against cerebral ischemia-reperfusion injury but the mechanisms of neuroprotection remain unclear. Calycosin and formononetin are two major AR isoflavones while daidzein is the metabolite of formononetin after absorption. Herein, we aim to investigate the synergistic neuroprotective effects of those isoflavones of Astragali Radix against cerebral ischemia-reperfusion injury. Calycosin, formononetin and daidzein were organized with different combinations whose effects observed in both in vitro and in vivo experimental models. In the in vitro study, primary cultured neurons were subjected to oxygen-glucose deprivation plus reoxygenation (OGD/RO) or l-glutamate treatment. In the in vivo study, rats were subjected to middle cerebral artery occlusion to induce cerebral ischemia and reperfusion. All three isoflavones pre-treatment alone decreased brain infarct volume and improved neurological deficits in rats, and dose-dependently attenuated neural death induced by l-glutamate treatment and OGD/RO in cultured neurons. Interestingly, the combined formulas of those isoflavones revealed synergistically activated estrogen receptor (estrogen receptors)-PI3K-Akt signaling pathway. Using ER antagonist and phosphatidylinositol 3-kinase (PI3K) inhibitor blocked the neuroprotective effects of those isoflavones. In conclusion, isoflavones could synergistically alleviate cerebral ischemia-reperfusion injury via activating ER-PI3K-Akt pathway.

scholarly journals Maraviroc, An Inhibitor of Chemokine Receptor Type 5, Alleviates Neuroinflammatory Response after Cerebral Ischemia/Reperfusion Injury via Regulating JNK Signaling

2021 ◽  
Author(s):  
Beilei Chen ◽  
Pingping Cao ◽  
Xin Guo ◽  
Xiaobo Li ◽  
Li Jiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Chemokine Receptor ◽  
Ischemia Reperfusion ◽  
Primary Microglia ◽  
Neuroprotective Effects ◽  
Jnk Signaling ◽  
Cerebral Ischemia Reperfusion ◽  
Different Doses

Abstract Neuroinflammation is a key factor that contributes to the secondary injury after cerebral ischemia/reperfusion (CI/R) injury. Chemokine receptor type 5(CCR5) has shown its pro-inflammatory effects during central nervous system (CNS) diseases. However, the role of CCR5 in CI/R injury is still unclear. In this study, we administered maraviroc (MVC,APEXBIO,UK-427857), a CCR5 antagonist, to the middle cerebral artery occlusion(MCAO) mice. In vivo studies showed that MVC was successively intraperitoneally (i.p.) with different doses (5, 20, or 50 mg/kg body weight) for 3 days after mice MCAO. MVC showed its neuroprotective effects in alleviating neurological deficits and infarct volumes after MCAO. The level of apoptosis and inflammation were remarkably decreased by MVC treatment after CI/R injury. Subsequently, primary microglia were stimulated with different doses of MVC (0.2, 2, 20 or 200nM) for 12h after oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. MVC significantly increased the viability of primary microglia after (OGD/R). The expression of pro-inflammatory cytokines (IL-1β and IL-6) in microglia were down-regulated by MVC treatment. Mechanistically, MVC also inhibited the secretion of IL-1β and IL-6 by microglia after OGD stimulation. Furthermore, the key components of NF-κB pathway were measured in vivo and in vitro after MCAO and OGD. MVC significantly inhibited the activity of NF-κB pathway in the above pathological environments. Finally, our data indicated that MVC treatment decreased the activation of JNK signaling pathway after CI/R injury in vivo and in vitro. The JNK activator anisomycin (AN，Beyotime，SC0132-5mg) reversed the neuroprotective effects of MVC, indicating that the JNK pathway is involved in the anti-inflammatory and anti-apoptotic mechanisms of MVC in CI/R injury. Our data demonstrated that CCR5 inhibition exhibits neuroprotective effects after CI/R injury. MVC, which is widely used for HIV treatment by its anti-virus effect, is a potential drug for the treatment of ischemic stroke in the future clinical trials.

scholarly journals Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 248 ◽  
Author(s):  
Liwei Tan ◽  
Chen Liang ◽  
Yeye Wang ◽  
Yu Jiang ◽  
Shengqiao Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
B Cell Lymphoma ◽  
Narrow Particle Size Distribution ◽  
Active Components ◽  
Cerebral Ischemia Reperfusion

Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (w/w) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy.

scholarly journals Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094585 ◽  
Author(s):  
Chengli Ling ◽  
Chang Lei ◽  
Manshu Zou ◽  
Xiong Cai ◽  
Yun Xiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Pc12 Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Objective The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, both in vitro and in vivo. Methods We first treated PC12 cells with cobalt chloride (CoCl2) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores. Results The half-inhibitory concentration of CoCl2 was 1.2 mM. Pretreatment with 10 µg ⋅ mL−1 apigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl2-induced injury in vitro. In addition, apigenin treatment in vivo significantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation. Conclusions Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injury in vitro and in vivo.

Diosmetin alleviated cerebral ischemia/reperfusion injury in vivo and in vitro by inhibiting oxidative stress via SIRT1/Nrf2 signaling pathway

2021 ◽  
Author(s):  
Zhigang Mei ◽  
Lipeng Du ◽  
Xiaolu Liu ◽  
Xiangyu Chen ◽  
Huan Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Nrf2 Signaling Pathway ◽  
Cerebral Ischemia Reperfusion Injury

Oxidative stress is known to play a pivotal role in the pathogenesis of cerebral ischemia reperfusion (I/R) injury. Accumulating studies have revealed that diosmetin (Dios) could protect against oxidative stress...

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