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 μM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 μM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 μM). All test compounds at concentrations 100-200 μM 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.

Original languageEnglish
Pages (from-to)1055-1074
Number of pages20
JournalEXCLI Journal
Volume13
Publication statusPublished - 09-09-2014

Fingerprint

hypoglycemic agents
Quercetin
Fructose
Hypoglycemic Agents
insulin resistance
Inhibitory Concentration 50
Insulin Resistance
fructose
Antioxidants
Insulin
rats
quercetin
inhibitory concentration 50
Glucose
glycation
Skeletal Muscle Fibers
testing
Glycogen
Lipid Peroxidation
DNA Damage

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Animal Science and Zoology
  • Pharmacology
  • Drug Discovery

Cite this

Nayak, Y., Venkatachalam, H., Daroji, V. K., Mathew, G., Jayashree, B. S., & Unnikrishnan, M. K. (2014). Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats. EXCLI Journal, 13, 1055-1074.
Nayak, Yogendra ; Venkatachalam, H. ; Daroji, Vijay Kumar ; Mathew, Geetha ; Jayashree, B. S. ; Unnikrishnan, M. K. / Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats. In: EXCLI Journal. 2014 ; Vol. 13. pp. 1055-1074.
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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 μM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 μM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 μM). All test compounds at concentrations 100-200 μM 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.",
author = "Yogendra Nayak and H. Venkatachalam and Daroji, {Vijay Kumar} and Geetha Mathew and Jayashree, {B. S.} and Unnikrishnan, {M. K.}",
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Nayak, Y, Venkatachalam, H, Daroji, VK, Mathew, G, Jayashree, BS & Unnikrishnan, MK 2014, 'Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats', EXCLI Journal, vol. 13, pp. 1055-1074.

Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats. / Nayak, Yogendra; Venkatachalam, H.; Daroji, Vijay Kumar; Mathew, Geetha; Jayashree, B. S.; Unnikrishnan, M. K.

In: EXCLI Journal, Vol. 13, 09.09.2014, p. 1055-1074.

Research output: Contribution to journalArticle

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T1 - Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats

AU - Nayak, Yogendra

AU - Venkatachalam, H.

AU - Daroji, Vijay Kumar

AU - Mathew, Geetha

AU - Jayashree, B. S.

AU - Unnikrishnan, M. K.

PY - 2014/9/9

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N2 - 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 μM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 μM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 μM). All test compounds at concentrations 100-200 μM 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.

AB - 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 μM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 μM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 μM). All test compounds at concentrations 100-200 μM 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.

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