PMID- 29339110 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20180904 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 216 DP - 2018 Apr 24 TI - In vitro anti-diabetic effect of flavonoids and pheophytins from Allophylus cominia Sw. on the glucose uptake assays by HepG2, L6, 3T3-L1 and fat accumulation in 3T3-L1 adipocytes. PG - 8-17 LID - S0378-8741(17)33331-7 [pii] LID - 10.1016/j.jep.2018.01.014 [doi] AB - BACKGROUND AND PURPOSE: Based on ethno-botanical information collected from diabetic patients in Cuba and firstly reported inhibition of PTP1B and DPPIV enzymes activities, Allophylus cominia (A. cominia) was identified as possible source of new drugs that could be used for the treatment of type 2 diabetes mellitus (T2-DM). EXPERIMENTAL APPROACH: in this study, the activity of the characterised extracts from A. cominia was tested on the glucose uptake using HepG2 and L6 cells, 3T3-L1 fibroblasts and adipocytes as well as their effect on the fat accumulation using 3T3-L1 adipocytes. KEY RESULTS: on 2-NBDG glucose uptake assay using HepG2 and L6 cells, extracts from A. cominia enhanced insulin activity by increasing glucose uptake. On HepG2 cells Insulin EC(50) of 93 +/- 21nM decreased to 13 +/- 2nM in the presence of the flavonoids mixture from A.cominia. In L6 cells, insulin also produced a concentration-dependent increase with an EC(50) of 28.6 +/- 0.7nM; EC(50) decreased to 0.08 +/- 0.02nM and 5 +/- 0.9nM in the presence of 100mug/ml of flavonoids and pheophytins mixtures, respectively. In 3T3-L1 fibroblasts, insulin had an EC(50) of >1000nM that decreased to 38 +/- 4nM in the presence of the flavonoids extract. However, in adipocytes, insulin produced a significant concentration-dependent increase and an EC(50) of 30 +/- 8nM was a further confirmation of the insulin responsiveness of the adipocytes to the insulin. At 100microg/ml, flavonoids and pheophytins extracts decreased fat accumulation in 3T3-L1 adipocytes by two folds in comparison to the control differentiated cells (p < 0.05). The crude extract of A. cominia did not show any enhancement of 2-NBDG uptake by 3T3-L1 adipocytes in the presence or absence of 100nM insulin. In addition, in fully differentiated adipocytes, both extracts produced significant decrease in lipid droplets in the cells and no lipid accumulation were seen after withdrawal of the extracts from the cell growth medium. However, there was no effect of both extracts on total protein concentration in cells as well as on Glut-4 transporters. CONCLUSIONS AND IMPLICATIONS: the pharmacological effects of the extracts from A. cominia observed in experimental diabetic models were shown in this study. A. cominia is potentially a new candidate for the treatment and management of T2-DM. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Semaan, D G AU - Semaan DG AD - Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom. Electronic address: dima.semaan@hotmail.com. FAU - Igoli, J O AU - Igoli JO AD - Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom; Department of Chemistry, University of Agriculture, PMB 2373 Makurdi, Nigeria. FAU - Young, L AU - Young L AD - Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom. FAU - Gray, A I AU - Gray AI AD - Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom. FAU - Rowan, E G AU - Rowan EG AD - Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, United Kingdom. FAU - Marrero, E AU - Marrero E AD - National Centre for Animal and Plant Health (Centro Nacional de Sanidad Agropecuaria), San Jose de las Lajas, Mayabeque, Cuba. LA - eng PT - Journal Article DEP - 20180112 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Flavonoids) RN - 0 (Glucose Transporter Type 4) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Pheophytins) RN - 0 (Plant Extracts) RN - 0 (Slc2a4 protein, mouse) RN - 9G2MP84A8W (Deoxyglucose) RN - EQF2794IRE (4-Chloro-7-nitrobenzofurazan) RN - JE4F4P486R (2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose) SB - IM MH - 3T3-L1 Cells MH - 4-Chloro-7-nitrobenzofurazan/*analogs & derivatives/metabolism MH - Adipocytes/*drug effects/metabolism MH - Adipogenesis/*drug effects MH - Animals MH - Deoxyglucose/*analogs & derivatives/metabolism MH - Dose-Response Relationship, Drug MH - Flavonoids/isolation & purification/*pharmacology MH - Glucose Transporter Type 4/metabolism MH - Hep G2 Cells MH - Hepatocytes/*drug effects/metabolism MH - Humans MH - Hypoglycemic Agents/isolation & purification/*pharmacology MH - Insulin/pharmacology MH - Lipid Droplets/drug effects/metabolism MH - Mice MH - Muscle, Skeletal/*drug effects/metabolism MH - Pheophytins/isolation & purification/*pharmacology MH - Phytotherapy MH - Plant Extracts/isolation & purification/*pharmacology MH - Plants, Medicinal MH - Rats MH - *Sapindaceae/chemistry MH - Time Factors OTO - NOTNLM OT - 3T3-L1 differentiation OT - Allophylus cominia OT - Glucose uptake OT - HepG2 cells OT - L6 cells EDAT- 2018/01/18 06:00 MHDA- 2018/09/05 06:00 CRDT- 2018/01/18 06:00 PHST- 2017/09/06 00:00 [received] PHST- 2017/12/12 00:00 [revised] PHST- 2018/01/11 00:00 [accepted] PHST- 2018/01/18 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2018/01/18 06:00 [entrez] AID - S0378-8741(17)33331-7 [pii] AID - 10.1016/j.jep.2018.01.014 [doi] PST - ppublish SO - J Ethnopharmacol. 2018 Apr 24;216:8-17. doi: 10.1016/j.jep.2018.01.014. Epub 2018 Jan 12.