Please use this identifier to cite or link to this item: https://hdl.handle.net/1/1779
Title: Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats
Authors: Mathew, Geetha ;Nayak, Y.;Venkatachalam, H.;Daroji, V.K.;Jayashree, B.S.
Issue Date: Sep-2014
Source: September 2014, Volume 13, pp. 1055 - 1074 eCollection
Journal title: EXCLI Journal
Abstract: Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin-resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin, creatinine and AGEs were decreased to near normal upon treatment with test compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma triglycerides, lipids, endogenous antioxidant defense and glycogen were restored in FD-fed rats after treatment with 3-hydroxyflavones. It is known that insulin resistance is partly because of oxidative stress and hence antioxidant activity was determined. They exhibited significant in vitro DPPH and ABTS radical scavenging activity (IC50: 10.66-66.63 microM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 microM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 microM). All test compounds at concentrations 100-200 microM protected calf thymus DNA-damage by Fenton reaction. In addition, test compounds inhibited protein glycation in different in vitro antiglycation assays. JY-2 showed maximum potency in all the stages of glycation which was comparable to the standard quercetin and aminoguanidine. Test compounds also enhanced the glucose uptake by L6 myotubes at an EC50 much lower than that of quercetin. Thus the synthetic 3-hydroxyflavones were found to have good antidiabetic activity by pleotropic and multimodal suppression of insulin resistance and enhancement of glucose uptake by skeletal muscles. These compounds are non-toxic at the doses tested. Further, the combined antioxidant and antiglycation activities of these molecules have complementary benefits in management of diabetes.
URI: https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1779
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26417321/
ISSN: 1611-2156
Publicaton type: Journal Article
Keywords: Research
Appears in Collections:Health Service Research

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