Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy

Myocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fission and mitophagy are essential factors for mitochondrial quality control, but whether they play key roles in cardiac I/R injury remains unknown. New pharmacological or molecular interventions to alleviate reperfusion injury are currently considered desirable therapies. Vitamin D3 (Vit D3) regulates cardiovascular function, but its physiological role in I/R-exposed hearts, especially its effects on mitochondrial homeostasis, remains unclear. An in vitro hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate myocardial I/R injury. H/R treatment significantly reduced H9c2 cell viability, increased apoptosis, and activated caspase 3. In addition, H/R treatment increased mitochondrial fission, as manifested by increased expression of phosphorylated dynein-related protein 1 (p-Drp1) and mitochondrial fission factor (Mff) as well as increased mitochondrial translocation of Drp1. Treatment with the mitochondrial reactive oxygen species scavenger MitoTEMPO increased cell viability and decreased mitochondrial fission. H/R conditions elicited excessive mitophagy, as indicated by increased expression of BCL2-interacting protein 3 (BNIP3) and light chain (LC3BII/I) and increased formation of autolysosomes. In contrast, Vit D3 reversed these effects. In a mouse model of I/R, apoptosis, mitochondrial fission, and mitophagy were induced. Vit D3 treatment mitigated apoptosis, mitochondrial fission, mitophagy, and myocardial ultrastructural abnormalities. The results indicate that Vit D3 exerts cardioprotective effects against I/R cardiac injury by protecting mitochondrial structural and functional integrity and reducing mitophagy.

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Receptor-Interacting Protein Kinase 3 Inhibition Prevents Cadmium-Mediated Macrophage Polarization and Subsequent Atherosclerosis via Maintaining Mitochondrial Homeostasis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.737652 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiexin Zhang ◽

Weijing Feng ◽

Minghui Li ◽

Peier Chen ◽

Xiaodong Ning ◽

...

Keyword(s):

Protein Kinase ◽

Macrophage Polarization ◽

Mitochondrial Fission ◽

Underlying Mechanism ◽

Interacting Protein ◽

Mitochondrial Homeostasis ◽

Cd Exposure ◽

M1 Type

Chronic cadmium (Cd) exposure contributes to the progression of cardiovascular disease (CVD), especially atherosclerosis (AS), but the underlying mechanism is unclear. Since mitochondrial homeostasis is emerging as a core player in the development of CVD, it might serve as a potential mechanism linking Cd exposure and AS. In this study, we aimed to investigate Cd-mediated AS through macrophage polarization and know the mechanisms of Cd-caused mitochondrial homeostasis imbalance. In vitro, flow cytometry shows that Cd exposure promotes M1-type polarization of macrophages, manifested as the increasing expressions of nuclear Factor kappa-light-chain-enhancer of activated B (NF-kB) and NLR family pyrin domain containing 3 (NLRP3). Mitochondrial homeostasis tests revealed that decreasing mitochondrial membrane potential and mitophage, increasing the mitochondrial superoxide (mROS), and mitochondrial fission are involved in the Cd-induced macrophage polarization. The upregulated expressions of receptor-interacting protein kinase 3 (RIPK3) and pseudokinase-mixed lineage kinase domain-like protein (p-MLKL) were observed. Knocking out RIPK3, followed by decreasing the expression of p-MLKL, improves the mitochondrial homeostasis imbalance which effectively reverses macrophage polarization. In vivo, the oil red O staining showed that Cd with higher blood significantly aggravates AS. Besides, M1-type polarization of macrophages and mitochondrial homeostasis imbalance were observed in the aortic roots of the mice through immunofluorescence and western blot. Knocking out RIPK3 restored the changes above. Finally, the administered N-acetyl cysteine (NAC) or mitochondrial division inhibitor-1 (Mdivi-1), which decreased the mROS or mitochondrial fission, inhibited the expressions of RIPK3 and p-MLKL, attenuating AS and macrophage M1-type polarization in the Cd-treated group. Consequently, the Cd exposure activated the RIPK3 pathway and impaired the mitochondrial homeostasis, resulting in pro-inflammatory macrophage polarization and subsequent AS. Knocking out RIPK3 provided a potential therapeutic target for Cd-caused macrophage polarization and subsequent AS.

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MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

Current Neurovascular Research ◽

10.2174/1567202617666200415154822 ◽

2020 ◽

Vol 17 (3) ◽

pp. 259-266 ◽

Cited By ~ 2

Author(s):

Xuan Chen ◽

Sumei Zhang ◽

Peipei Shi ◽

Yangli Su ◽

Dong Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Therapeutic Option ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Small Gtpase ◽

Luciferase Reporter ◽

Pathological Feature ◽

In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

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Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons

Cell Death and Disease ◽

10.1038/s41419-021-03752-2 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Anthony R. Anzell ◽

Garrett M. Fogo ◽

Zoya Gurm ◽

Sarita Raghunayakula ◽

Joseph M. Wider ◽

...

Keyword(s):

Cortical Neurons ◽

Ischemia Reperfusion Injury ◽

Mitochondrial Dynamics ◽

Ischemia Reperfusion ◽

Mitochondrial Fission ◽

Conditional Knockout ◽

Mitochondrial Morphology ◽

Primary Neurons ◽

Mitochondrial Fragmentation

AbstractMitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.

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Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction

Clinical Science ◽

10.1042/cs20180671 ◽

2018 ◽

Vol 132 (20) ◽

pp. 2163-2167 ◽

Cited By ~ 11

Author(s):

Hannah A. Cooper ◽

Satoru Eguchi

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Molecular Mechanisms ◽

Ischemia Reperfusion ◽

Mitochondrial Fission ◽

Future Research ◽

Mitochondrial Homeostasis ◽

Acute Mi ◽

Future Research Directions ◽

Receive Treatment

Ischemia reperfusion (I/R) injury is a common event following myocardial infarction (MI) resulting in excessive oxidative stress, calcium overload, inflammation, and cardiomyocyte death. Mitochondrial homeostasis including their dynamics are imbalanced in cardiac I/R injury in favor of increased mitochondrial fission. Inhibition of mitochondrial fission prior to I/R injury is protective and improves cardiac function following MI. Clinically, patients with MI often receive treatment following initiation of the ischemic event. Thus, treatments with more realistic timing would have better translational value and are important to research. In a recent study published in Clinical Science, Maneechote et al. [Clin. Sci. (2018) 132, 1669–1683] examined the effect of inhibiting mitochondrial fission using the mitochondrial division inhibitor (Mdivi-1) at different time points, pre-ischemia, during-ischemia, and upon onset of reperfusion, in a rat cardiac I/R model. The findings showed the greatest cardiac function improvement with pre-ischemia treatment along with decreased mitochondrial fragmentation and increased mitochondrial function. Mdivi-1 given during ischemia and at onset of reperfusion also improved cardiac function, but to a lesser extent than pre-ischemia intervention. Maneechote et al. postulated that the LV protection by Mdivi-1 in cardiac I/R could be due to an improvement in mitochondrial dysfunction through attenuating excessive mitochondrial fission which then reduces apoptotic myocytes. Their findings provide new insights into future treatment of patients suffering acute MI which could consider targetting the excessive mitochondrial fission during cardiac ischemia or at onset of reperfusion. Here, we will further discuss the background of the study, potential molecular mechanisms of mitochondrial fission, consequences of the fission, and future research directions.

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LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.747802 ◽

2021 ◽

Vol 8 ◽

Author(s):

Cuizhi Li ◽

Huafeng Song ◽

Chunlin Chen ◽

Shaoxian Chen ◽

Qiyu Zhang ◽

...

Keyword(s):

Myocardial Ischemia ◽

Cell Viability ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

H9c2 Cells ◽

Myocardial Ischemia Reperfusion ◽

Tissue Specimens ◽

Masson Staining

Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

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Inhibitory effects of Panax ginseng glycoproteins in models of doxorubicin-induced cardiac toxicity in vivo and in vitro

Food & Function ◽

10.1039/d1fo01307f ◽

2021 ◽

Author(s):

Yajun Chen ◽

Lei Wang ◽

Tianjia Liu ◽

Zhidong Qiu ◽

Ye Qiu ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Cell Viability ◽

Panax Ginseng ◽

Cardiac Toxicity ◽

H9c2 Cell ◽

Inhibitory Effects ◽

Myocardial Oxidative Stress

We investigated the protective effect of PGP against DOX-induced cardiotoxicity in vitro and in vivo. PGP increases H9C2 cell viability and inhibits apoptosis, alleviating DOX-induced myocardial oxidative stress-related cardiotoxicity.

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Abstract 203: Regulation of Lipid Phosphate Phosphatase 3 in Cardiac Ischemia/Reperfusion Injury and Hypertrophy

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.203 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Mini Chandra ◽

Jonathan Fox ◽

Wayne Orr ◽

Christopher Kevil ◽

Sumitra Miriyala ◽

...

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Negative Regulator ◽

Cardiomyocyte Hypertrophy ◽

Acute Mi ◽

Lipid Phosphate ◽

Lipid Phosphate Phosphatases ◽

Old Mice

Generation of reactive oxygen species (ROS) has been implicated in myocardial infarction (MI), stroke and sudden cardiac death. Mitochondrial respiration is a major source of ROS production and lipids regulate mitochondrial oxidative metabolism and homeostasis through effects on mitochondrial fusion and fission and on the activity of mitochondrial membrane proteins. Lipid phosphate phosphatases (LPPs) control the conversion of bioactive lipid phosphates to their dephosphorylated counterparts. These include phosphatidic acid (PA), and lysophosphatidic acid (LPA). Oxidative stress was identified to transactivate microRNA-92a, which is a negative regulator of LPP3. We found that LPP3 expression was markedly down regulated in ischemic regions after ischemia/reperfusion (I/R) injury. We observed a similar trend in the myocardium from patients with acute MI at 24h. Our in vitro studies indicate that overexpression of LPP3 protects the cardiomyocyte against ROS-induced cardiac injury and reduction of LPP3 by conditional specific cardiac knockout of the LPP3 gene in mice increases cardiac dysfunction and mortality. These mice are viable and fertile but showed increased mortality ~8 months (Fig1). Blood pressure was similar in LPP3 fl/fl (96 ± 9 mmHg; n = 19) and Myh6- LPP3 Δ mice (92 ± 7 mmHg; n = 19), although heart rates were significantly higher in Myh6- LPP3 Δ 3 month old mice (642 ± 21 bpm, compared to LPP3 fl/fl with 600± 17 bpm; P<0.001). Knockdown of LPP3 enhanced cardiomyocyte hypertrophy induced by LPA based on analysis of sarcomere organization, cell surface area, levels of fetal genes ANP and BNP, and ANF release from nuclei, which are hallmarks of cardiomyocyte hypertrophy, indicating that LPP3 negatively regulates cardiomyocyte hypertrophy induced by LPA.

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LncRNA PVT1 Mediated by ZFP36L2 Regulates Myocardial Ischemia/Reperfusion Injury and Attenuates Mitochondrial Fusion and Fission via Activating miR-21-5p/MARCH5 Axis

10.21203/rs.3.rs-108063/v1 ◽

2020 ◽

Author(s):

Weifeng Huang ◽

Qin Tan ◽

Yong Guo ◽

Yongmei Cao ◽

Jiawei Shang ◽

...

Keyword(s):

Zinc Finger Protein ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mitochondrial Fission ◽

Tumor Biology ◽

Luciferase Reporter ◽

Mitochondrial Morphology ◽

Mrna Levels

Abstract BackgroundAmong several leading cardiovascular disorders, ischemia-reperfusion (I/R) injury causes severe manifestations including acute heart failure, inflammation, and systemic dysfunction. Recently, there has been increasing evidence suggesting that alterations in mitochondrial morphology play a role in the prognoses of cardiac disorders. Long non-coding RNAs (lncRNAs) form major regulatory networks to modify gene transcription and translation. While several roles of lncRNAs have been explored in cancer and tumor biology, their implications on mitochondrial morphology and functions remain to be elucidated. MethodsThe functional roles of ZFP36L2 and lncRNA PVT1 were determined by a series of cardiomyocyte hypoxia/ reoxygenation (H/R) in vitro and myocardial I/R injury in vivo experiments. Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analysis were used to detect the mRNA levels of ZFP36L2 and mitochondrial fission and fusion markers in the myocardial tissues and cardiomyocyte. Cardiac function was determined by immunohistochemistry, H&E, Masson’s staining and echocardiogram. Ultrastructural analysis of mitochondrial fission was performed using transmission electron microscopy (TEM). The mechanistic model of PVT1 with ZFP36L2 and miR-21-5p with MARCH5 was detected by subcellular fraction, RNA pull down, FISH, and luciferase reporter assays.ResultsIn this study, we report a novel regulatory axis involving lncRNA PVT1, microRNA miR-21-5p, and E3 ubiquitin ligase MARCH5, which alters mitochondrial morphology during myocardial I/R injury. Using an in vivo I/R injury mouse model and in vitro cardiomyocyte H/R model, we observed that zinc finger protein ZFP36L2 directly associated with PVT1 and altered mitochondrial fission and fusion. PVT1 also interacted with miR-21-5p and suppressed its expression and activity. Furthermore, we identified MARCH5 as a modifier of miR-21-5p, and expression of MARCH5 and its effect on mitochondrial fission and fusion were directly proportional to PVT1 expression during H/R injury. ConclusionsOur findings demonstrated that manipulation of PVT1-miR-21-5p-MARCH5-mediated mitochondrial fission and fusion via ZFP36L2 may be a novel therapeutic approach to regulate myocardial I/R injury.

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Abstract P049: Circadian Clock Dysfunction Impairs Mitochondrial Fitness And Contributes To Myocardial Ischemic Injury

Hypertension ◽

10.1161/hyp.76.suppl_1.p049 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Inna Rabinovich-Nikitin ◽

Illana Posen ◽

Victoria Margulets ◽

Tami A Martino ◽

Lorrie A Kirshenbaum

Keyword(s):

Quality Control ◽

Cell Viability ◽

Circadian Clock ◽

Cardiac Myocytes ◽

Mitochondrial Dynamics ◽

Ischemia Reperfusion ◽

Mitochondrial Fission ◽

Control Mechanisms ◽

Complex Activity ◽

Mitochondrial Dynamic

Cardiac function is highly reliant on mitochondrial oxidative metabolism and fitness. The circadian clock is critically linked to vital physiological process including mitochondrial fission, fusion and quality control mechanisms. However, little is known of how the circadian clock regulates these vital processes in the heart. Herein, we identified a putative circadian Clock - mitochondrial interactome that gates an adaptive stress response for cell viability during myocardial ischemia reperfusion (I-R) injury. We show that Clock transcriptionally coordinates expression of mitochondrial dynamic fusion and fission, bioenergetic and quality control proteins in cardiac myocytes. Transcriptome and gene ontology mapping revealed Clock defective hearts subjected to I-R exhibited major transcriptional deficits in several key survival processes including mitochondrial dynamics, bioenergetics and autophagy that were reduced further following I-R. Gain of function of Clock activity re-established gene transcription of mitochondrial respiratory complex activity, quality control mechanisms and cell viability. Collectively, our data show that mitochondrial fitness and cell survival is mutually dependent upon and obligatorily linked to transcription of the circadian Clock gene in cardiac myocytes. Our data suggest the functional loss of Clock activity predisposes cardiac myocytes to metabolic catastrophe. Hence, therapeutic strategies designed to preserve circadian clock activity in the hearts may prove beneficial in reducing morbidity and mortality following ischemia -related pathologies such as myocardial infarction.

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The Role of Astragaloside IV against Cerebral Ischemia/Reperfusion Injury: Suppression of Apoptosis via Promotion of P62-LC3-Autophagy

Molecules ◽

10.3390/molecules24091838 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1838 ◽

Cited By ~ 13

Author(s):

Yi Zhang ◽

Ying Zhang ◽

Xiao-fei Jin ◽

Xiao-hong Zhou ◽

Xian-hui Dong ◽

...

Keyword(s):

Cell Viability ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Sprague Dawley ◽

Astragaloside Iv ◽

Ht22 Cells ◽

Sd Rats ◽

Neurological Score

Background: Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury, and autophagy plays a role in the pathology. Astragaloside IV is a potential neuroprotectant, but its underlying mechanism on cerebral I/R injury needs to be explored. The objective of this study is to investigate the neuroprotective mechanism of Astragaloside IV against cerebral I/R injury. Methods: Middle cerebral artery occlusion method (MCAO) and oxygen and glucose deprivation/reoxygenation (OGD/R) method were used to simulate cerebral I/R injury in Sprague-Dawley (SD) rats and HT22 cells, respectively. The neurological score, 2,3,5-Triphe-nyltetrazolium chloride (TTC) staining, and transmission electron microscope were used to detect cerebral damage in SD rats. Cell viability and cytotoxicity assay were tested in vitro. Fluorescent staining and flow cytometry were applied to detect the level of apoptosis. Western blotting was conducted to examine the expression of proteins associated with autophagy. Results: This study found that Astragaloside IV could decrease the neurological score, reduce the infarct volume in the brain, and alleviate cerebral I/R injury in MCAO rats. Astragaloside IV promoted cell viability and balanced Bcl-2 and Bax expression in vitro, reduced the rate of apoptosis, decreased the expression of P62, and increased the expression of LC3II/LC3I in HT22 cells after OGD/R. Conclusions: These data suggested that Astragaloside IV plays a neuroprotective role by down-regulating apoptosis by promoting the degree of autophagy.

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