Abbas Manal Ahmad, Oriquat Ghaleb Ali, Abbas Manal Mohamed, Al-Najjar Belal Omar, Kandil Yasser Ibrahim
Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan.
Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
Malays J Med Sci. 2020 Dec;27(6):39-52. doi: 10.21315/mjms2020.27.6.5. Epub 2020 Dec 29.
Dyslipidaemias are common in patients with diabetes mellitus. A high prevalence of type 2 diabetes in hyperlipidaemic patients also exists. The aim of this study was to find a treatment that lowers both blood glucose and lipid levels simultaneously.
The hypolipidaemic effect of (R)-(-)-carvone was investigated in a tyloxapol-induced hyperlipidaemia mice model. Furthermore, its effect on insulin secretion and proliferation of 1.1E7 human pancreatic β-cells was studied. In addition, using molecular docking, the binding affinity of (R)-(-)-carvone against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase was estimated.
(R)-(-)-carvone (100 mg/kg) decreased plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index by 90.6%, 49.3%, 56.6% and 70.3%, respectively, but it had no effect on high-density lipoprotein cholesterol (HDL-C). Furthermore, it increased hepatic triglyceride level and catalase activity by 79.6% and 59.6%, respectively. In-vitro, 500 μM (R)-(-)-carvone increased insulin secretion by 454.4% and proliferation of 1.1E7 cells with no cytotoxic effects up to a concentration of 100 μM. Molecular docking simulation demonstrated a good binding affinity with -5.03 Kcal/mol of (R)-(-)-carvone to HMG-CoA reductase.
The hypolipidaemic effect of (R)-(-)-carvone is comparable to that of fenofibrate. (R)-(-)-carvone has the advantage over fenofibrate of not producing hypoglycaemia in animals. Furthermore, (R)-(-)-carvone increased proliferation and insulin secretion of human pancreatic β-cells.
血脂异常在糖尿病患者中很常见。高脂血症患者中2型糖尿病的患病率也很高。本研究的目的是找到一种能同时降低血糖和血脂水平的治疗方法。
在吐温80诱导的高脂血症小鼠模型中研究了（R）-（-）-香芹酮的降血脂作用。此外，还研究了其对1.1E7人胰腺β细胞胰岛素分泌和增殖的影响。另外，通过分子对接，估算了（R）-（-）-香芹酮与3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的结合亲和力。
（R）-（-）-香芹酮（100mg/kg）可使血浆甘油三酯、总胆固醇、低密度脂蛋白胆固醇（LDL-C）水平和动脉粥样硬化指数分别降低90.6%、49.3%、56.6%和70.3%，但对高密度脂蛋白胆固醇（HDL-C）无影响。此外，它还使肝脏甘油三酯水平和过氧化氢酶活性分别增加了79.6%和59.6%。在体外，500μM（R）-（-）-香芹酮可使胰岛素分泌增加454.4%，并使1.1E7细胞增殖，在浓度高达100μM时无细胞毒性作用。分子对接模拟显示（R）-（-）-香芹酮与HMG-CoA还原酶具有良好的结合亲和力，结合能为-5.03千卡/摩尔。
（R）-（-）-香芹酮的降血脂作用与非诺贝特相当。（R）-（-）-香芹酮相对于非诺贝特的优势在于在动物中不会产生低血糖。此外，（R）-（-）-香芹酮可增加人胰腺β细胞的增殖和胰岛素分泌。
