A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury

Huang, Kaiyu; Yu, Yong-Wei; Liu, Shuai; Zhou, Yingying; Wang, Jinsheng; Peng, Yu; Ji, Kangting; Xue, Yan

doi:10.3389/fphar.2021.642925

Cited by 8 publications

(9 citation statements)

References 44 publications

(63 reference statements)

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“…Previous studies have shown that Astragalus propinquus Schischkin and its main active components astragaloside IV and astragalus polysaccharide can exert cardioprotective effects in vitro and in vivo , which are specifically manifested in inhibiting myocardial cell death, reducing oxidative stress, reducing autophagosome accumulation, reducing myocardial fibrosis. and myocardial remodeling, thereby improving cardiac function and reducing cardiac ischemia-reperfusion injury ( Ma et al, 2013 ; Liu et al, 2018 ; Jiang et al, 2019 ; Huang et al, 2021 ; Zhang et al, 2022 ). Salvia miltiorrhiza Bunge, with tanshinone IIa, salvianolic acid A and B as the main active ingredients, has also been proven to prevent and treat MI, cardiac hypertrophy and cardiac fibrosis ( Li et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway

Zhang

Huang²,

Song³

et al. 2023

Front. Pharmacol.

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Astragalus propinquus Schischkin and Salvia miltiorrhiza Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors β (PDGFR-β), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor β (TGF-β). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.

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Section: Discussionmentioning

confidence: 99%

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway

Zhang

Huang²,

Song³

et al. 2023

Front. Pharmacol.

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“…According to the DMTD diagram and previous reports, AS IV and PAE were considered might be the key components of YTC against MI. It has been reported that AS IV could protect heart from MI and reperfusion injury through a variety of ways, including regulating autophagy, oxidative stress and energy metabolisms ( Tu et al, 2013 ; Jiang et al, 2019 ; Huang et al, 2021 ). In addition, a study suggested that PAE had protective effect on myocardial ischemia-reperfusion by inhibiting apoptosis and reducing oxidative stress ( Wu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrated Approach Based on Network Analysis Combined With Experimental Verification Reveals PI3K/Akt/Nrf2 Signaling Is an Important Way for the Anti-Myocardial Ischemia Activity of Yi-Qi-Tong-Luo Capsule

Duan

Liu³

et al. 2022

Front. Pharmacol.

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Background:Yiqi-Tongluo Capsule (YTC) is a Chinese traditional patent medicine that has been used in the treatment of myocardial ischemia (MI). However, its molecular mechanisms against MI have not been clear.Methods: Network analysis and experimental verification were used to explore the potential molecular mechanisms of YTC for MI treatment. Firstly, the main components in the capsules and the potential targets of these components were predicted by online databases. The MI related genes were collected from Genecards and Online Mendelian Inheritance in Man (OMIM) databases. The drug targets and disease targets were intersected, and then the protein-protein interaction (PPI) and Drug-Molecular-Target-Disease Network (DMTD) were constructed, and GO enrichment analysis and KEGG pathway enrichment analysis were performed. Based on the H2O2-stimulated H9c2 cells, flow cytometry, western blot (WB) and immunofluorescence experiments were performed to verify the network analysis prediction.Results: A total of 100 active components and 165 targets of YTC were predicted, in which there were 109 targets intersected with the targets of MI. GO and KEGG analysis showed that these potential targets were related to a variety of biological processes and molecular mechanisms, including oxidative stress and PI3K/AKT pathway. Astragaloside IV (AS IV) and paeoniflorin (PAE) might be the main active components in YTC. The results of cell counting kit-8 (CCK-8) showed that YTC alleviated the damage of H2O2 to H9c2 cells. The results of flow cytometry, DAPI staining and JC-1 probe showed that YTC alleviated H2O2 induced apoptosis in H9c2 cells. In addition, YTC reduced the level of intracellular superoxide anion, increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA) in H2O2-induced H9c2 cells. The results of immunofluorescence and WB showed that the phosphorylation of PI3K and Akt were increased, the expression of Bcl-2 was up-regulated and the expression of cleaved caspase-3 and Bax were down-regulated. Besides, the nuclear translocation of Nrf2 were increased.Conclusion: In conclusion, the results of this study showed that YTC might alleviate MI by suppressing apoptosis induced by oxidative stress via the PI3K/Akt/Nrf2 signal pathway.

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“…It has been shown that NLRP3 inflammasome is activated by mitochondrial oxidative stress (24,31). To further clarify whether the SOD2 acetylation is related to NLRP3 activation, the SOD2 inhibitor 2-ME2 was treated in PC12 cells immediately after SI (23,32,33). Results showed that 2-ME2 could significantly inhibit SOD2 expression, while SOD2 Ac-K122 level increased at 6 h after SI, and using 2-ME2 could significantly enhance SI-induced NLRP3 and cleaved caspase-1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…PC12 cells and primary astrocytes were incubated into modified 6-well plates (BioFLEX, Hillsborough, USA), and equiaxial stretch (20%, 0.5-Hz frequency) was applied for 2 h using a Flexcell FX-4000TTM Tension System (Flexcell Int, Hillsborough, USA). To clarify the effects and signaling relationship of PD, SOD2 and NLRP3 on SI, MCC950 (10 uM) (14), SOD2 inhibitor 2-methoxyestradiol (2-ME2, 10 uM) (23), and PD (50 uM) (17), respectively, were applied immediately after SI and then placed in a 37°C, 5% CO 2 incubator for 6 h for following experiments. PC12 and primary astrocytes that were not stretched were considered controls.…”

Section: Methodsmentioning

confidence: 99%

Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

Zhao

et al. 2022

Shock

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Traumatic brain injury (TBI) is a kind of disease with high morbidity, mortality, and disability, and its pathogenesis is still unclear. Research shows that nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) activation in neurons and astrocytes is involved in neuroinflammatory cascades after TBI. What is more, polydatin (PD) has been shown to have a protective effect on TBI-induced neuroinflammation, but the mechanisms remain unclear. Here, we speculated that PD could alleviate TBI-induced neuroinflammatory damage through the superoxide dismutase (SOD2)-NLRP3 signal pathway, and SOD2 might regulate NLRP3 inflammasome activation. The model of lateral fluid percussion for in vivo and cell stretching injury for in vitro were established to mimic TBI. NLRP3 chemical inhibitor MCC950, SOD2 inhibitor 2-methoxyestradiol, and PD were administered immediately after TBI. As a result, the expression of SOD2 acetylation (SOD2 Ac-K122), NLRP3, and cleaved caspase-1 were increased after TBI both in vivo and in vitro, and using SOD2 inhibitor 2-methoxyestradiol significantly promoted SOD2 Ac-K122, NLRP3, and cleaved caspase-1 expression, as well as exacerbated mitochondrial ROS (mtROS) accumulation and mitochondrial membrane potential (MMP) collapse in PC12 cells. However, using NLRP3 inhibitor MCC950 significantly inhibited cleaved caspase-1 activation after TBI both in vivo and in vitro; meanwhile, MCC950 inhibited mtROS accumulation and MMP collapse after TBI. More importantly, PD could inhibit the level of SOD2 Ac-K122, NLRP3, and cleaved caspase-1 and promote the expression of SOD2 after TBI both in vivo and in vitro. Polydatin also inhibited mtROS accumulation and MMP collapse after stretching injury. These results indicated that PD inhibited SOD2 acetylation to alleviate NLRP3 inflammasome activation, thus acting a protective role against TBI neuroinflammation.

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A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury

Cited by 8 publications

References 44 publications

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway

An Integrated Approach Based on Network Analysis Combined With Experimental Verification Reveals PI3K/Akt/Nrf2 Signaling Is an Important Way for the Anti-Myocardial Ischemia Activity of Yi-Qi-Tong-Luo Capsule

Polydatin ameliorates TBI induced secondary brain injury by inhibiting NLRP3-induced neuroinflammation associated with SOD2 acetylation

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