Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Abstract

Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nuclear factor (NF)-κB. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.

Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway

“…The occurrence of autophagy and apoptosis is accompanied by the inhibition of AKT/mTOR signalling pathway . Moreover, studies have shown that muscone can induce phosphorylation of AKT during myocardial infarction in mice . Consistent with this phenomenon, our study discovered that the expression of phosphorylated AKT and mTOR was inhibited in RSC 96 cells treated with HG, while the expression trend of phosphorylated AKT and mTOR was reversed after treated with muscone.…”

“…Previous studies have demonstrated that muscone has anti‐apoptotic effect on myocardial remodelling in myocardial infarction mice . It has been reported that apoptosis of SCs is one of the characteristics of DPN .…”

Muscone Induces CYP1A2 and CYP3A4 Enzyme Expression in L02 Human Liver Cells and CYP1A2 and CYP3A11 Enzyme Expression in Kunming Mice

“…Muscone is a compound found in traditional herbs that is used in China for preventing several diseases and for decreasing the onset of symptoms occurring in patients [4,5,6,7,8,9]. In this study, a preliminary toxicity profile of muscone is presented with extensions to the inductive propensities of the latter compound on CYP1A2 and CYP3A4 expression levels.…”

“…Although musk was initially obtained from natural sources, its extensive use has led to chemical synthesis that resulted in the emergence of 3 major classes of musk compounds, notably aromatic nitro compounds, polycyclic musk compounds, and macrocyclic musk compounds [4]. Muscone is one of the macrocyclic musk compounds that is well known for the characteristic odor of musk and has been extensively studied as a natural preventive medicine for a variety of disorders [4,7,8,9]. In the 2012 version of the national pharmacopoeia, approximately 10% of Chinese medicines, such as Angongniuhuang and Suhexiang pills, contained musk.…”

Muscone Ameliorates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κb Ligand-Induced Osteoclastogenesis by Suppressing TNF Receptor–Associated Factor 6-Mediated Signaling Pathways

“…Muscone (MUS), 3-methylcyclopentadecanone, is the main ingredient of musk ( Figure 1A). It is used to treat myocardial infarction (Wang et al, 2014;Du et al, 2018), relieve pain, and promote fractures . Furthermore, it has been proved to have anti-inflammatory effects on multiple systems (Wang et al, 2014;Liu et al, 2014).…”