Scutellarin protects against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation

Xu, Lijiao; Chen, Rongchang; Ma, Xiaoyu; Zhu, Yue; Sun, Guibo

doi:10.1016/j.phymed.2020.153169

Cited by 71 publications

(79 citation statements)

References 28 publications

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“…Consistent with our findings, scutellarin suppressed NLRP3 inflammasome activation in macrophages 35 . Meanwhile, scutellarin also protected against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation 45 .…”

Section: Discussionmentioning

confidence: 99%

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Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.

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Section: Discussionmentioning

confidence: 99%

“…Then, we are the first to report that scutellarin inhibits the activation of NLRP3 in pulmonary fibrosis. Up till now, there are only two reports about scutellarin inhibiting NLRP3, one in sepsis 22 and the other in myocardial ischemia reperfusion 45 . Besides, this is the first report that scutellarin inhibits EMT in pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

et al. 2020

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“…Cardiac function was assessed using M-mode echocardiography according to the methods described in our previous study [ 16 ]. Briefly, rats were anesthetized with 2% isoflurane, and echocardiography was performed using a Vevo 770 high-resolution in vivo imaging system (FUJIFILM VisualSonics, Inc., Toronto, Ontario, Canada).…”

Section: Methodsmentioning

confidence: 99%

Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

Wang

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.

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“…Subsequently, NLRP3 processes the secretion of inflammatory cytokines, including IL‐1β and IL‐18 ( Deretic and Levine, 2018 ). Therefore, inhibition of NLRP3 activation can inhibit the secretion of inflammatory factors, thereby reducing myocardial injury caused by I/R ( Xu et al, 2020 ; Wu et al, 2020 ). In view of the important role of NLRP3 in MI/R injury, we examined the effect of HSYA on NLRP3 inflammasomes and the secretion of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

“…Myocardial ischemia was inflicted by ligating the left anterior descending coronary artery ( Xu et al, 2020 ). Briefly, 90 rats were anesthetized through intraperitoneal injection of pentobarbital sodium (40 mg/kg), intubated in the supine position, and monitored using electrocardiogram.…”

Section: Methodsmentioning

confidence: 99%

Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury via Suppressing NLRP3 Inflammasome and Activating Autophagy

Ye¹,

Lu²,

Wang³

et al. 2020

Front. Pharmacol.

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Myocardial ischemia/reperfusion (MI/R) injury is a serious threat to human health. Hydroxysafflor yellow A (HSYA), the main water-soluble ingredient extracted from Carthami flos ( Carthamus tinctorius L.), has therapeutic potential for treating MI/R injury. However, the mechanisms of HSYA−mediated protection from MI/R injury are incompletely understood. In the present study, we investigated the effects and the underlying mechanisms of HSYA during MI/R. Adult Sprague-Dawley rats were subjected to left anterior descending artery ligation for 30 min followed by 24 h of reperfusion with or without HSYA treatment. The protective effect of HSYA was detected by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin eosin (HE) staining, and myocardial enzymes detections. Serum levels of inflammatory factors such as TNF-α, interleukin (IL)-1β, and IL-18, were detected using ELISA kits. The expression of NLRP3 and other related proteins in the myocardium was detected by western blot and immunohistochemistry. The expression of autophagy-related proteins, including Atg5, BECN1, P62, and LC3B, was detected by western blot to evaluate the effect of HSYA on autophagy. Results showed that HSYA decreased the myocardial infarct size and attenuated the cardiac dysfunction in rats after I/R. In addition, HSYA inhibited myocardial apoptosis compared with the I/R group, decreased the levels of inflammatory cytokines in rat serum, reduced NLRP3 inflammasome expression, and induced autophagy. Mechanistically, our results demonstrated that HSYA can activate AMPK to improve autophagy and inhibit NLRP3 inflammasome by inhibiting the mTOR pathway. This work provides strong data supporting for the clinical applications of HSYA in MI/R injury.

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Scutellarin protects against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation

Cited by 71 publications

References 28 publications

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

Hydroxysafflor Yellow A Protects Against Myocardial Ischemia/Reperfusion Injury via Suppressing NLRP3 Inflammasome and Activating Autophagy

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