Mokashi Priyanka, Khanna Aparna, Pandita Nancy
Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India.
Department of Chemistry, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India.
Biomed Pharmacother. 2017 Jun;90:268-277. doi: 10.1016/j.biopha.2017.03.047. Epub 2017 Mar 30.
Diabetes mellitus has spread over the world with 347 million people affected. Insulin resistance is a main pathogenic event in Type 2 Diabetes Mellitus (T2DM) leading to a reduction in glucose uptake by peripheral tissue and increased hepatic glucose output. In this study, we have isolated four flavonoid rich fractions fraction A (FA), fraction B (FB), fraction C (FC) and fraction D (FD) from Enicostema littorale. All the fractions were preliminary screened for TLC fingerprinting, total flavonoid content. Total eight flavonoids were identified by LC/MS. Insulin resistant HepG2 (IR/HepG2) model was established by inducing insulin resistance in HepG2 cells to investigate the effect of these fractions on IR/HepG2 cell line for their glucose uptake. The results showed the significant dose dependant increase in glucose uptake of cells treated with FD. It showed significant activity at a concentration of 10μg/ml. The LC/MS results of FD demonstrated the presence of C-glycoside Swertisin which could be responsible for the effect. Further, to investigate the mechanism of action, gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. A significant upregulation of these genes was observed in FD treated samples, thereby indicating the enhancement of glucose uptake rate of cells via IRS-1/PI3K/Akt pathway.
糖尿病已在全球蔓延，有3.47亿人受到影响。胰岛素抵抗是2型糖尿病（T2DM）的主要致病因素，导致外周组织对葡萄糖的摄取减少以及肝脏葡萄糖输出增加。在本研究中，我们从滨海肋柱花中分离出四个富含黄酮类化合物的组分：组分A（FA）、组分B（FB）、组分C（FC）和组分D（FD）。对所有组分进行了TLC指纹图谱、总黄酮含量的初步筛选。通过LC/MS鉴定出总共八种黄酮类化合物。通过在HepG2细胞中诱导胰岛素抵抗建立胰岛素抵抗HepG2（IR/HepG2）模型，以研究这些组分对IR/HepG2细胞系葡萄糖摄取的影响。结果显示，用FD处理的细胞的葡萄糖摄取呈显著的剂量依赖性增加。它在浓度为10μg/ml时表现出显著活性。FD的LC/MS结果表明存在C-糖苷獐牙菜苷，这可能是造成该效应的原因。此外，为了研究作用机制，通过实时PCR评估胰岛素受体底物1（IRS-1）、蛋白激酶B（Akt-2）和葡萄糖转运蛋白4（GLUT-4）基因的表达。在FD处理的样品中观察到这些基因显著上调，从而表明通过IRS-1/PI3K/Akt途径提高了细胞的葡萄糖摄取率。
