Duangjai Acharaporn, Ontawong Atcharaporn, Srimaroeng Chutima
Division of Physiology, School of Medical Sciences, University of Phayao, Phayao, Thailand.
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Res Pharm Sci. 2019 Jun;14(3):190-200. doi: 10.4103/1735-5362.258485.
var. ) () leaf extract, a traditional ayurvedic medicine, has been reported to exhibit antipyretic, antibacterial, antidyslipidemic, and antihyperglycemia effects. This study investigated the mechanism of hypocholesterolemic effect of methanolic extract of Siamese neem flowers in studies and in Caco-2 cells. Pancreatic cholesterol esterase and 3-hydroxy 3-methylglutaryl-CoA (HMG-CoA) reductase activities were assessed. Cholesterol micelle formation was prepared for cholesterol physicochemical property analyses, micelle size and solubility, and transport of cholesterol into the Caco-2 cells. The expression of niemann-pick C1 like 1 (NPC1L1), and its major regulator, peroxisome proliferator-activated receptor δ (PPARδ), were determined by western blot and real time polymerase chain reaction, respectively. A. indica flower extract inhibited pancreatic cholesterol esterase activity and increased cholesterol micelles size. Uptake of cholesterol into Caco-2 cells was inhibited by flower extract in a dose-dependent manner. In addition, extract inhibited HMG-CoA reductase activity, resulting in low level of intracellular cholesterol accumulation, together with increased cytosolic NPC1L1 protein expression and decreased PPARδ gene expression. In conclusion, flower extract has cholesterol-lowering effects by inhibiting intestinal cholesterol absorption, interfering micellar cholesterol formation, and attenuating cholesterol synthesis. As such, flower extract has potential for developing into nutraceutical product for prevention of hypocholesterolemia.
传统阿育吠陀药物印楝花提取物据报道具有解热、抗菌、抗血脂异常和降血糖作用。本研究在动物实验和Caco-2细胞中探究了暹罗印楝花甲醇提取物降胆固醇作用的机制。评估了胰腺胆固醇酯酶和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的活性。制备胆固醇胶束用于胆固醇物理化学性质分析、胶束大小和溶解度以及胆固醇向Caco-2细胞的转运。分别通过蛋白质印迹法和实时聚合酶链反应测定尼曼-匹克C1样1蛋白（NPC1L1）及其主要调节因子过氧化物酶体增殖物激活受体δ（PPARδ）的表达。印楝花提取物抑制胰腺胆固醇酯酶活性并增加胆固醇胶束大小。印楝花提取物以剂量依赖方式抑制胆固醇向Caco-2细胞的摄取。此外，提取物抑制HMG-CoA还原酶活性，导致细胞内胆固醇积累水平降低，同时胞质NPC1L1蛋白表达增加，PPARδ基因表达降低。总之，印楝花提取物通过抑制肠道胆固醇吸收、干扰胶束胆固醇形成和减弱胆固醇合成而具有降胆固醇作用。因此，印楝花提取物有开发成预防低胆固醇血症营养保健品的潜力。
