PMID- 28364599 OWN - NLM STAT- MEDLINE DCOM- 20180220 LR - 20191210 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 90 DP - 2017 Jun TI - Flavonoids from Enicostema littorale blume enhances glucose uptake of cells in insulin resistant human liver cancer (HepG2) cell line via IRS-1/PI3K/Akt pathway. PG - 268-277 LID - S0753-3322(16)32973-0 [pii] LID - 10.1016/j.biopha.2017.03.047 [doi] AB - 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 10mug/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. CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Mokashi, Priyanka AU - Mokashi P AD - Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India. FAU - Khanna, Aparna AU - Khanna A AD - Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India. FAU - Pandita, Nancy AU - Pandita N AD - Department of Chemistry, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India. Electronic address: nancy.pandita@nmims.edu. LA - eng PT - Journal Article DEP - 20170330 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (C-glycoside) RN - 0 (Flavonoids) RN - 0 (Glucose Transporter Type 4) RN - 0 (Glycosides) RN - 0 (IRS1 protein, human) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Monosaccharides) RN - 0 (Plant Extracts) RN - EC 2.7.10.1 (Receptor, Insulin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Cell Line, Tumor MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Flavonoids/*pharmacology MH - Gentianaceae/*chemistry MH - Glucose/*metabolism MH - Glucose Transporter Type 4/metabolism MH - Glycosides MH - Hep G2 Cells MH - Humans MH - Insulin/metabolism MH - Insulin Receptor Substrate Proteins/*metabolism MH - Insulin Resistance/*physiology MH - Liver Neoplasms MH - Monosaccharides/pharmacology MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphorylation/drug effects MH - Plant Extracts/pharmacology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Receptor, Insulin/metabolism MH - Signal Transduction/drug effects MH - Up-Regulation/drug effects OTO - NOTNLM OT - E. littorale OT - Flavonoids OT - Glucose transporters OT - Glucose uptake assay OT - HepG2 cell line OT - Insulin receptors OT - LC/MS EDAT- 2017/04/02 06:00 MHDA- 2018/02/21 06:00 CRDT- 2017/04/02 06:00 PHST- 2016/12/29 00:00 [received] PHST- 2017/03/03 00:00 [revised] PHST- 2017/03/18 00:00 [accepted] PHST- 2017/04/02 06:00 [pubmed] PHST- 2018/02/21 06:00 [medline] PHST- 2017/04/02 06:00 [entrez] AID - S0753-3322(16)32973-0 [pii] AID - 10.1016/j.biopha.2017.03.047 [doi] PST - ppublish SO - Biomed Pharmacother. 2017 Jun;90:268-277. doi: 10.1016/j.biopha.2017.03.047. Epub 2017 Mar 30.