Abstract
Lipid metabolism disorders lead to vascular endothelial injury. Matrine is an alkaloid that has been used to improve obesity and diabetes and for the treatment of hepatitis B. However, its effect on lipid metabolism disorders and vascular injury is unclear. Here, we investigated the effect of matrine on high‐fat diet fed mice and oxidized low‐density lipoprotein (ox‐LDL)‐induced human umbilical vein endothelial cells (HUVECs). Computational virtual docking analyses, phosphoinositide 3‐kinase (PI3K) and protein kinase C‐α (PKCα) inhibitors were used to localize matrine in vascular injuries. The results showed that matrine‐treated mice were more resistant to abnormal lipid metabolism and inflammation than vehicle‐treated mice and exhibited significantly alleviated ox‐LDL‐stimulated dysfunction of HUVECs, restored diminished nitric oxide release, decreased reactive oxygen species generation and increased expression phosphorylation of AKT‐Ser473 and endothelial nitric oxide synthase (eNOS)‐Ser1177. Matrine not only up‐regulates eNOS‐Ser1177 but also down‐regulates eNOS‐Thr495, a PKCα‐controlled negative regulator of eNOS. Using computational virtual docking analyses and biochemical assays, matrine was also shown to influence eNOS/NO via PKCα inhibition. Moreover, the protective effects of matrine were significantly abolished by the simultaneous application of PKCα and the PI3K inhibitor. Matrine may thus be potentially employed as a novel therapeutic strategy against high‐fat diet‐induced vascular injury.
Highlights
With the rapid development of the global economy and improvements in lifestyle, the overweight and obesity epidemic has become a major health challenge around the world.[1]
Obesity is a chronic metabolic disorder that is associated with numerous diseases, including hyperlipidemia, diabetes mellitus, hypertension, atherosclerosis, cardiovascular disease and cancer.[26,27,28,29]
Abnormal metabolism of blood lipids caused by an HFD is the main cause of cardiovascular disease and increased plasma low‐density lipoprotein (LDL) levels are regarded as a major risk factor
Summary
With the rapid development of the global economy and improvements in lifestyle, the overweight and obesity epidemic has become a major health challenge around the world.[1]. Vascular endothelial cell injury plays an important role in the pathological process. In Asia, S flavescens and S subprostrata are commonly used in meat soups and are thought to improve obesity and diabetes.[11] Mat has been widely used in the clinic for the treatment hepatitis B and has exhibited a number of therapeutic effects on cardiovascular diseases.[12,13] Mat can protect cardiomyocytes from ischemia/reperfusion injury and can improve isoproterenol‐induced myocardial injury via regulating nitric oxide synthase.[14,15] the mechanisms of Mat in endothelial vascular injury due to lipid metabolism disorders have not been studied. The present study explored the possible molecular pathways of Mat in relation to its cardiovascular protective effects
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