The atheroprotective roles of heart-protecting musk pills against atherosclerosis development in apolipoprotein E-deficient mice

Abstract

Background: Heart-protecting musk pill (HMP), derived from Chinese herbal medicines, has been found to possess protective roles against atherosclerosis-related cardiovascular diseases (CVDs), however, the antiatherosclerotic mechanisms of HMP are still unclear. Here, we investigated the effects of HMP on alleviating atherosclerotic lesion severity in mice and explored the molecular mechanisms.Methods: Apolipoprotein E-deficient mice were fed western-type diet supplemented with HMP (25 mg/kg/day) or normal saline gavage for 20 weeks. Then histopathological staining was performed to assess the atheromatous plaque burden. Biochemical kits were used to detect levels of lipid profiles. Moreover, effector factors associated with lipid metabolism in liver and intestinal tissues were investigated by western blot and real-time PCR assays. Levels of signal molecules participating in the mitochondrial-mediated apoptosis pathway were detected by Western blot.Results: We found that HMP notably reduced atherosclerotic lesion size (P<0.05) and improved plaque stability (P<0.05). HMP treatment decreased circulating TC (P<0.01), LDL-C (P<0.01) and TG (P<0.05) levels and increased HDL-C (P<0.05) content. HMP was found to suppress SREBP2, HMGCR and PCSK9 expressions (P<0.05), yet promote LDLR expression (P<0.05) in hepatocytes. Moreover, HMP was discovered to activate PPARα/CPT-1A cascade (P<0.05) and inhibit contents of SREBP1c and the lipogenic genes FAS and ACCα (P<0.05). The LBK1/AMPK cascade was also activated after HMP administration (P<0.05). Additionally, HMP was found to facilitate transintestinal cholesterol excretion by increasing ABCG5 and ABCG8 levels and reducing NPC1L1 content (P<0.05). In terms of vasoprotective activities, we observed that HMP decreased cleaved caspase-3 content (P<0.05) in the vascular intima, which might be due to inhibition of mitochondrial-related signaling pathway.Conclusions: Altogether, our study indicates that HMP plays anti-atherosclerotic roles via regulating lipid metabolism and improving vascular intimal injury.

MFGE8, ALB, APOB, APOE, SAA1, A2M, and C3 as Novel Biomarkers for Stress Cardiomyopathy

“…Apolipoprotein is a protein that can bind and transport blood lipids to tissues for metabolism and utilization [ 30 ]. A large number of studies have found that apolipoprotein gene mutation can affect blood lipid metabolism and utilization, thus growing up to be a risk factor for cardiovascular and cerebrovascular diseases, diabetes, and other diseases [ 31 , 32 ]. APOE and APOB are members of the apolipoprotein family, and so far, no studies have shown a direct relationship between apolipoprotein and SCM.…”

“…Cardiovascular Therapeutics utilization, thus growing up to be a risk factor for cardiovascular and cerebrovascular diseases, diabetes, and other diseases [31,32]. APOE and APOB are members of the apolipoprotein family, and so far, no studies have shown a direct relationship between apolipoprotein and SCM.…”

Effect of Traditional Chinese Medicine Poge Heart‐Saving Decoction on Cardiac Function in Heart Failure Rat Model

“…Musk is a valuable and costly ingredient in Chinese medicine. Heart-protecting musk pills were used to treat coronary disease and heart failure [ 31 , 32 ]. Kimura et al [ 33 ] found that musk strengthened the effect of catecholamine to enhance heart function.…”

Eastern Remedies for Western-type diet induced atherosclerosis

“…The biosynthesis of both cholesterol and fatty acids was downregulated by HMP while cholesterol clearance from the blood via LDL-receptor and fatty acid clearance via β-oxidation was increased. Finally, HMP treatment had a beneficial effect on vascular intimal injury by suppressing apoptosis and increasing NO production in endothelial cells (8).…”

“…In the current issue of Annals of Translational Medicine, Lu et al report about the beneficial effect of Heartprotecting Musk Pills (HMP) in an established model of atherosclerosis, the apolipoprotein E (ApoE) deficient mouse (8), which is prone to develop atherosclerosis on high fat, Western-type diet due to a poor clearance of cholesterol-containing lipoprotein from the blood. HMP are derived from a classical formula in TCM, also known Editorial as Shexiang Baoxin Pills, which dates back to the Song Dynasty (960-1279).…”