Inhibition of myocardial hypertrophy by magnesium isoglycyrrhizinate through the TLR4/NF-κB signaling pathway in mice

Ma, Donglai; Zhang, Jianping; Zhang, Yuanyuan; Zhang, Xuan; Han, Xue; Song, Tao; Zhang, Ying; Chu, Li

doi:10.1016/j.intimp.2017.12.019

Cited by 61 publications

(33 citation statements)

References 32 publications

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“…The treated group showed a reduction in mRNA expression of ANP, BNP, c-fos, and c-jun thereby proving its antifibrotic action. Moreover, reduction in protein expression of TLR4 and NFκB demonstrated by western blots supported the antiinflammatory and antifibrotic action of magnesium salt of glyzyrrhizic acid (Ma et al, 2018). However, detailed molecular studies are warranted to further understand the mechanisms behind the observed protection.…”

Section: Glycyrrhizia Glabra (Glycyrrhizic Acid)mentioning

confidence: 81%

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Allawadhi

Khurana

Sayed

et al. 2018

Phytotherapy Research

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Heart is the most active and incumbent organ of the body, which maintains blood flow, but due to various pathological reasons, several acute and chronic cardiac complications arise out of which myocardial infarction is one of the teething problems. Isoproterenol (ISP)-induced myocardial ischemia is a classical model to screen the cardioprotective effects of various pharmacological interventions. Phytochemicals present a novel option for treating various human maladies including those of the heart. A large number of plant products and their active ingredients have been screened for efficacy in ameliorating ISP-induced myocardial ischemia including coriander, curcumin, Momordica, quercetin, and Withania somnifera. These phytochemicals constituents may play key role in preventing disease and help in cardiac remodeling. Reactive oxygen species scavenging, antiinflammatory, and modulation of various molecular pathways such as Nrf2, NFкB, p-21 activated kinase 1 (PAK1), and p-smad2/3 signaling modulation have been implicated behind the claimed protection. In this review, we have provided a focused overview on the utility of ISP-induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis for preclinical research. In addition, we have also surveyed molecular mechanism of various plant-based interventions screened for cardioprotective effect in ISP-induced cardiotoxicity, and their probable mechanistic profile is summarized.

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Section: Glycyrrhizia Glabra (Glycyrrhizic Acid)mentioning

confidence: 81%

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Allawadhi

Khurana

Sayed

et al. 2018

Phytotherapy Research

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“…pressure overload-induced myocardial hypertrophy through NF-B and TLR9. 41,42 As with TLR4 and TLR9, TLR3 is expressed in cardiomyocytes and it stimulates NF-B activity, but little is known about its role in the heart. In our study, hypertrophic stimulation…”

Section: I S C L a I M E R : T H E M A N U S C R I P T A N D I T S mentioning

confidence: 99%

SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation

Tang¹,

Pan²,

Zhao³

et al. 2020

Circulation

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Background: S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of cardiovascular disease. The aim of this study was to determine the role of SNO of MLP (muscle LIM protein) in myocardial hypertrophy, as well as the mechanism by which SNO-MLP modulates hypertrophic growth in response to pressure overload. Methods: Myocardial samples from patients and animal models exhibiting myocardial hypertrophy were examined for SNO-MLP level using biotin-switch methods. SNO sites were further identified through liquid chromatography–tandem mass spectrometry. Denitrosylation of MLP by the mutation of nitrosylation sites or overexpression of S-nitrosoglutathione reductase was used to analyze the contribution of SNO-MLP in myocardial hypertrophy. Downstream effectors of SNO-MLP were screened through mass spectrometry and confirmed by coimmunoprecipitation. Recruitment of TLR3 (Toll-like receptor 3) by SNO-MLP in myocardial hypertrophy was examined in TLR3 small interfering RNA–transfected neonatal rat cardiomyocytes and in a TLR3 knockout mouse model. Results: SNO-MLP level was significantly higher in hypertrophic myocardium from patients and in spontaneously hypertensive rats and mice subjected to transverse aortic constriction. The level of SNO-MLP also increased in angiotensin II– or phenylephrine-treated neonatal rat cardiomyocytes. S-nitrosylated site of MLP at cysteine 79 was identified by liquid chromatography–tandem mass spectrometry and confirmed in neonatal rat cardiomyocytes. Mutation of cysteine 79 significantly reduced hypertrophic growth in angiotensin II– or phenylephrine-treated neonatal rat cardiomyocytes and transverse aortic constriction mice. Reducing SNO-MLP level by overexpression of S-nitrosoglutathione reductase greatly attenuated myocardial hypertrophy. Mechanistically, SNO-MLP stimulated TLR3 binding to MLP in response to hypertrophic stimuli, and disrupted this interaction by downregulating TLR3-attenuated myocardial hypertrophy. SNO-MLP also increased the complex formation between TLR3 and RIP3 (receptor-interacting protein kinase 3). This interaction in turn induced NLRP3 (nucleotide-binding oligomerization domain–like receptor pyrin domain containing 3) inflammasome activation, thereby promoting the development of myocardial hypertrophy. Conclusions: Our findings revealed a key role of SNO-MLP in myocardial hypertrophy and demonstrated TLR3-mediated RIP3 and NLRP3 inflammasome activation as the downstream signaling pathway, which may represent a therapeutic target for myocardial hypertrophy and heart failure.

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“…Animals in the ISO group were gavaged with 0.9% normal saline (10 mg kg −1 day −1 ) and injected subcutaneously with ISO (10 mg kg −1 day −1 ). [69] Animals in L-6-Gin and H-6-Gin groups were gavaged with 6-Gin (10, 20 mg kg −1 day −1 ) [70] www.advancedsciencenews.com www.mnf-journal.com and injected subcutaneously with ISO (10 mg kg −1 day −1 ). Animals in Pro group were given intraperitoneal injection of Pro (40 mg kg −1 ) and injected subcutaneously with normal saline (10 mg kg −1 day −1 ).…”

Section: Experiments Sectionmentioning

confidence: 99%

[6]‐Gingerol Ameliorates ISO‐Induced Myocardial Fibrosis by Reducing Oxidative Stress, Inflammation, and Apoptosis through Inhibition of TLR4/MAPKs/NF‐κB Pathway

Han

Liu

et al. 2020

Molecular Nutrition Food Res

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Scope [6]‐Gingerol is one of the primary pungent constituents of ginger. While [6]‐gingerol has many pharmacological effects, its benefits for myocardial fibrosis, including its exact role and underlying mechanisms, remain largely unexplored. The present study is designed to characterize the cardio‐protective effects of [6]‐gingerol in myocardial fibrosis mice and possible underlying mechanisms. Methods and results Mice are subcutaneously injected with isoproterenol (ISO, 10 mg kg−1) and gavaged with [6]‐gingerol (10, 20 mg kg−1 day−1) for 14 days. Pathological alterations, fibrosis, oxidative stress, inflammation response, and apoptosis are examined. In ISO‐induced myocardial fibrosis, [6]‐gingerol treatment decreases the J‐point, heart rate, cardiac weight index, left ventricle weight index, creatine kinase (CK), and lactate dehydrogenase serum levels, calcium concentration, reactive oxygen species, malondialdehyde, and glutathione disulfide (GSSG), and increases levels of superoxide dismutase, catalase, glutathione, and GSH/GSSG. Further, [6]‐gingerol improved ISO‐induced morphological pathologies, inhibited inflammation and apoptosis, and suppressed the toll‐like receptor‐4 (TLR4)/mitogen‐activated protein kinases (MAPKs)/nuclear factor κB (NF‐κB) signaling pathways. Conclusion The protective effect of [6]‐gingerol in mice with ISO‐induced myocardial fibrosis may be related to the inhibition of oxidative stress, inflammation, and apoptosis, potentially through the TLR4/MAPKs/NF‐κB signaling pathway.

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Inhibition of myocardial hypertrophy by magnesium isoglycyrrhizinate through the TLR4/NF-κB signaling pathway in mice

Cited by 61 publications

References 32 publications

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention

SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)–Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation

[6]‐Gingerol Ameliorates ISO‐Induced Myocardial Fibrosis by Reducing Oxidative Stress, Inflammation, and Apoptosis through Inhibition of TLR4/MAPKs/NF‐κB Pathway

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