Promoting effect of baicalin on nitric oxide production in CMECs via activating the PI3K-AKT-eNOS pathway attenuates myocardial ischemia–reperfusion injury

Bai, Jiannan; Wang, Qingchao; Qi, Jiaxin; Yu, Hongqiang; Wang, Cong; Wang, Xiaowei; Ren, Yanru; Yang, Fude

doi:10.1016/j.phymed.2019.153035

Cited by 61 publications

(51 citation statements)

References 55 publications

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“…Luan et al (2019) revealed that baicalin attenuated myocardial I/R-induced damage, inhibited myocardial apoptosis and inflammation by Akt/NF-jB signalling. Bai et al (2019) showed that baicalin protected cardiac microvascular endothelial cells (CMECs) in I/R rats by promoting the release of nitric oxide. However, it was still of interest to determine if baicalin could induce macrophages to regulate inflammatory response and protect myocardial injury post-I/R.…”

Section: Introductionmentioning

confidence: 99%

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Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

Song

2020

Pharmaceutical Biology

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Context: Baicalin is an active compound which demonstrates cardioprotection effects against myocardial ischaemia/reperfusion injury (MI/RI). Objective: To investigate how baicalin protects against myocardial injury and to explore its potential mechanism. We hypothesized that baicalin-modulated macrophages change from M1 (pro-inflammatory subset) to M2 (anti-inflammatory subset) under I/R stress. Materials and methods: We established an ischaemia/reperfusion (I/R) model using Sprague Dawley (SD) rat, then baicalin was intragastric administration (20, 60 or 120 mg/kg) for 24 h. The rats were randomly divided into five groups (n ¼ 10): control, I/R, I/R þ baicalin (20 mg/kg), I/R þ baicalin (60 mg/kg) and I/R þ baicalin (120 mg/kg). Cardiac function was detected by echocardiography, HE staining and ELISA, respectively. Macrophage phenotype was examined by flow cytometry. Furthermore, IHC, qRT-PCR and WB were employed to analyse the related mechanisms. Results: The study showed that baicalin (20, 60 or 120 mg/kg) significantly improved cardiac function and impeded cardiac apoptosis in rats. In addition, the repair of myocardial morphology (reduced neutrophil infiltration) further confirmed its cardiacprotective effect. Moreover, baicalin effectively decreased iNOS, IL-1b and IL-6, and up-regulated Arg-1, IL-10 and TGF-b via changing the macrophage phenotype (from M1 towards M2). Notably, treatment with baicalin also inhibited the phosphorylation levels of JAK2 and STAT3. Discussion and conclusions: It was confirmed that baicalin alleviated post-I/R myocardial injury and reduced inflammation via JAK/STAT pathway, and baicalin treatment might be recommended as a new approach for myocardial ischaemic complications.

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Section: Introductionmentioning

confidence: 99%

“…Bai et al. ( 2019 ) showed that baicalin protected cardiac microvascular endothelial cells (CMECs) in I/R rats by promoting the release of nitric oxide. However, it was still of interest to determine if baicalin could induce macrophages to regulate inflammatory response and protect myocardial injury post-I/R.…”

Section: Introductionmentioning

confidence: 99%

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

Song

2020

Pharmaceutical Biology

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“…Emerging evidence suggests that necroptosis might be a primary mode of cardiomyocyte death following reoxygenation, given that approximately 50% of cellular death could be reduced by blocking necroptosis, while pancaspase inhibitor, z‐VAD, only reduced cellular death by 30% 30 . Lactate dehydrogenase (LDH), creatine kinase (CK), and troponin‐I are indicators for myocardial injury, and those markers were detected in various types of cardiomyocytes subjected to H/R including an embryonic myoblast cell line (H9c2), neonatal rat ventricular myocytes (NRVM), neonatal mouse cardiac myocytes (NMCM), and cardiac microvascular endothelial cells (CMEC) 24‐27,29‐31 . This information is summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…Several mechanisms including distal embolization, oxidative stress, cellular/interstitial oedema, endothelial dysfunction, vasoconstriction, and inflammation have been implicated in the pathogenesis of microvascular dysfunction 36,37 . CMECs were used to study the potential role of necroptosis on endothelial function 29,30 . The expression levels of platelet endothelial cell adhesion molecule (PECAM‐1), nitric oxide (NO), platelet‐derived growth factor receptor beta (PDGFRβ) mRNA, and angiotensin II (Ang II) mRNA were significantly downregulated in CMECs after H/R, possibly through inhibition of the phosphatidylinositol 3‐kinase/protein kinase B/endothelial NO synthase (PI3K/Akt/eNOS) survival pathway 29 .…”

Section: Introductionmentioning

confidence: 99%

The role of RIPK3‐regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia‐reperfusion injury

2020

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Despite advancements in management of acute myocardial infarction, this disease remains one of the leading causes of death. Timely reestablishment of epicardial coronary blood flow is the cornerstone of therapy; however, substantial amount of damage can occur as a consequence of cardiac ischaemia/reperfusion (I/R) injury. It has been previously proposed that the pathway leading to major cell death, apoptosis, is responsible for cardiac I/R injury. Nevertheless, there is compelling evidence to suggest that necroptosis, a programmed necrosis, contributes remarkably to both myocardial injury and microcirculatory dysfunction following cardiac I/R injury. Receptor‐interacting protein kinase 1 (RIPK1), RIPK3, and mixed‐lineage kinase domain‐like pseudokinase (MLKL) are shown as the major mediators of necroptosis. In addition to the traditional perception that RIPK1/RIPK3/MLKL‐dependent plasma membrane rupture is fundamental to this process, several RIPK3‐related pathways such as endoplasmic reticulum stress and mitochondrial fragmentation have also been implicated in cardiac I/R injury. In this review, reports from both in vitro and in vivo studies regarding the roles of necroptosis and RIPK3‐regulated necrosis in cardiac I/R injury have been collectively summarized and discussed. Furthermore, reports on potential interventions targeting these processes to attenuate cardiac I/R insults to the heart have been presented in this review. Future investigations adding to the knowledge obtained from these previous studies are needed in the pursuit of discovering the most effective pharmacological agent to improve cardiac I/R outcomes.

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“…Additionally, endothelial mitochondrial oxidative stress is implicated in senescent vascular events, and AMPK plays a defensive role in this stress during senescence [14]. The phosphoinositide-3-kinase (PI3K)/AKT signaling pathway is crucial in regulating endothelial function and injury [15]. AKT, the downstream effector of PI3K, encourages cell survival in response to various causes of cell death by mediating EC survival and inducing the production of nitric oxide (NO) by activating eNOS [16].…”

Section: Introductionmentioning

confidence: 99%

SIRT1-Mediated Protective Effect of Aralia elata (Miq.) Seem against High-Glucose-Induced Senescence in Human Umbilical Vein Endothelial Cells

Kim

2019

Nutrients

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Aralia elata (Miq.) Seem (AS) is widely been for treating many diseases, enhancing energy, and boosting immunity; however, its protective effects against high-glucose (HG)-triggered endothelial dysfunction and the potential underlying mechanisms have not been investigated. In this study, we determined the effect of AS on senescence in human umbilical vein endothelial cells (HUVECs) and elucidated the mechanisms underlying its anti-aging effects. The senescence model of endothelial cells (ECs) was established by culturing HUVECs in media containing HG (30 mM). We found that the proportion of senescent (senescence-associated β-galactosidase+) cells in the HG group was significantly higher than that in the control group; however, this increase was suppressed by AS treatment. Moreover, cell cycle analysis revealed that AS (20 μg/mL) significantly recovered HG-induced cell cycle arrest in ECs, and Western blot revealed that AS prevented HG-induced decreases in silent information regulator 1 (SIRT1) level and endothelial nitric oxide synthase (eNOS) phosphorylation. These results show that AS delayed HG-induced senescence in ECs by modulation of the SIRT1/5′ AMP-activated protein kinase and AKT/eNOS pathways.

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Promoting effect of baicalin on nitric oxide production in CMECs via activating the PI3K-AKT-eNOS pathway attenuates myocardial ischemia–reperfusion injury

Cited by 61 publications

References 55 publications

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

The role of RIPK3‐regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia‐reperfusion injury

SIRT1-Mediated Protective Effect of Aralia elata (Miq.) Seem against High-Glucose-Induced Senescence in Human Umbilical Vein Endothelial Cells

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