Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signaling in rat septic shock

Zhang, Minghao; Wang, Xiuyu; Wang, Xiumei; Hou, Xiaolin; Teng, Peng; Jiang, Yideng; Zhang, Linna; Yang, Xia; Tian, Jianwei; Li, Guizhong; Cao, Jun; Xu, Hui; Li, Yunhong; Wang, Yin

doi:10.3892/mmr.2013.1315

Cited by 43 publications

(38 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spontaneously hypertensive rats, oxymatrine prevents ventricular remodeling, myocardial hypertrophy, and cardiac fibrosis [12]. Oxymatrine also exhibits anti-inflammatory activity, which protects against myocardial injury in septic shock [14]. The protective effect of oxymatrine on aldosterone-induced myocardial injury has been shown to be similar to the effect of spironolactone, a competitive aldosterone inhibitor [13].…”

Section: Discussionmentioning

confidence: 96%

“…Its anti-oxidative activity has been useful in the treatment of liver fibrosis, viral hepatitis, skin diseases, and autoimmune disease [8]. Recently, oxymatrine has been extensively studied for its protective effects against heart injuries induced by isoproterenol [9], myocardial ischemia [10, 11], hypertension [12], aldosterone [13], septic shock [14], and arrhythmias [15]. However, the effects of oxymatrine on doxorubicin-induced cardiotoxicity have not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

Zhang

Huang

2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

Zhang

Huang

2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Zhang et al found that the increased levels of the TNF‐α and IL‐1β proteins induced by cecal ligation and puncture and the cardiac muscle injury induced by septic shock were markedly attenuated by OM treatment in a dose‐dependent manner in rats. The edema, degeneration, and necrosis of the myocardial tissues were significantly reduced following the administration of OM, which has been found to parallel the levels of the JAK2 and STAT3 proteins (Zhang et al , ). Similarly, Wang et al found that the levels of TNF‐α and IL‐1β in renal tissue were decreased following administration with OM in a rat model of septic shock.…”

Section: Introductionmentioning

confidence: 85%

Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine

2016

View full text Add to dashboard Cite

Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of oxymatrine might include the TGF-β/Smad, toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol-3 kinase/Akt, delta-opioid receptor-arrestinl-Bcl-2, CD40, epidermal growth factor receptor, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this review, we summarize the recent investigations of the signaling pathways related to oxymatrine to provide clues and references for further studies on its clinical application. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

“…1). It has been used for the treatment of inflammatory diseases, various types of cancer, heart injury induced by myocardial ischemia [11], hypertension [12], and septic shock [13], and previous studies have shown that it is effective against ischemia and reperfusion injury [14]. The effective mechanisms may be the inhibition of oxidative stress, inflammation, and induction of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Inhibits Homocysteine-Mediated Autophagy via MIF/mTOR Signaling in Human Umbilical Vein Endothelial Cells

Zhang

Zhang²,

Tang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Genetic or nutritional deficiencies in homocysteine (Hcy)metabolism lead to the accumulation of Hcy and its metabolites in the blood. This can lead to hyperhomocysteinemia (HHcy), which is an independent risk factor for cardiovascular disease. Studies have shown that HHcy leads to endothelial dysfunction, a hallmark of atherosclerosis, which may explain this link. The precise mechanism remains unclear, but a strong possibility is excessive HHCy-induced autophagy. Autophagy has been better studied in ischemia/reperfusion (I/R) injuries, and previous work showed that Oxymatrine (OMT), a quinolizidine alkaloid, protects cells against myocardial I/R injury by inhibiting autophagy. The aim of this study was to determine whether OMT inhibits autophagy in HHcy. Methods: Autophagy in HUVEC cells treated with Hcy in the presence and absence of OMT was visualized bytransmission electron microscopy and the degree was determined by western blotting and qRT-PCR. Small interfering RNA (siRNA)was used to determine the efficiency of Macrophage migration inhibitory factor (MIF) inhibition. Cell apoptosis wasdetected by western blotting and flow cytometric analysis. Results: OMT inhibited autophagy, MIF, and mTOR in HUVECs during Hcy exposure, depending on the dose. siRNA-mediated MIF knockdown decreased Hcy-induced autophagy, while administration of 3-methyladenosine and rapamycin showed that they also induce autophagy. Furthermore, OMT dose-dependently inhibited the Hcy-induced HUVEC apoptosis/death. Conclusions: These results suggest that Hcy can evokeautophagy-activated HUVEC apoptosis/death via a MIF/mTOR signaling pathway, which can be reversed by OMT. Our results provide a new insight into a functional role of OMT in the prevention of Hcy-induced HUVEC injury and death.

show abstract

Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signaling in rat septic shock

Cited by 43 publications

References 19 publications

Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats

Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine

Oxymatrine Inhibits Homocysteine-Mediated Autophagy via MIF/mTOR Signaling in Human Umbilical Vein Endothelial Cells

Contact Info

Product

Resources

About