Artemisinin Attenuates Post-Infarct Myocardial Remodeling by Down-Regulating the NF-κB Pathway

Abstract

Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.

Discovery of novel small molecule inhibitors of cardiac hypertrophy using high throughput, high content imaging

“…Indeed, half of the 2015 Nobel Prize in Physiology and Medicine was awarded to the investigator who discovered artemisinin, a drug that is estimated to reduce malaria-associated mortality by 20% overall, and by >30% in children [28]. Artemisinin was previously shown to reduce LV hypertrophy in rat models of pressure overload and myocardial infarction, in association with blunted NF-κB signaling in the heart [29,30]. Unlike artemisinin, which is a natural product, artesunate is a semisynthetic derivative that has improved solubility, bioavailability and anti-malarial activity [31].…”

Total Flavones of Choerospondias axillaris Attenuate Cardiac Dysfunction and Myocardial Interstitial Fibrosis by Modulating NF-κB Signaling Pathway

“…We speculated that NF-jB signaling pathway play a vital role in the development of this process. Previous studies have shown that the stimulation or induction of MMPs at the transcriptional level is regulated by a variety of growth factors and inflammatory cytokines, many of them are modulated by NF-jB [25]. NF-jB, a heterodimeric cytosolic protein, is kept inactive in resting cells by binding with a member of the IKBa inhibitor protein family.…”

Retracted: ‘Anti‐fibrotic actions of Ghrelin by inhibition of the NADPH oxidase–ROS signaling pathway’ by Qian Wang, Xin Sui, Rui Chen, Peiyong Ma, Tao Ding, Dianjun Sui, and Ping Yang

“…The LV was cut into 5 mm sections and stained with Masson's trichrome. Images were acquired at 400x magnification using a fluorescence microscopy, and the degree of interstitial fibrosis and perivascular fibrosis were determined using Image-Pro Plus 6.0 software (Media Cybernetics, Rockville, MD, USA) as previously described [48] .…”