Skip to main content
Top
Published in: Neurological Sciences 7/2014

01-07-2014 | Original Article

Flavonoid, morin inhibits oxidative stress, inflammation and enhances neurotrophic support in the brain of streptozotocin-induced diabetic rats

Authors: Mohammad S. Ola, Abdulaziz M. Aleisa, Salim S. Al-Rejaie, Hatem M. Abuohashish, Mihir Y. Parmar, Abdullah S. Alhomida, Mohammed M. Ahmed

Published in: Neurological Sciences | Issue 7/2014

Login to get access

Abstract

Diabetes-induced damages in brain are known as diabetic encephalopathy, which is well characterized by cellular, molecular and functional changes in the brain of diabetic subjects and rodents. However, little is known about the mechanism of damages and the therapeutic strategies in ameliorating those damages in the diabetic brain. In this study, we utilized a flavonoid, morin which is emerging as a potent drug against a wide range of free radical-mediated as well as neurodegenerative diseases. Morin (15 and 30 mg/kg body weight/day) was orally administered to two different groups of rats after 1 week of diabetes induction, and continued for five consecutive weeks. Two other untreated groups of diabetic and non-diabetic rats were used to compare with drug-treated groups. After drug treatments, cerebral cortex of the brain harvested and analyzed for different factors. Morin supplementation especially at high dose increased the levels of insulin, reduced glutathione, superoxide dismutase and catalase activities, and decreased fasting glucose and thiobarbituric acid reactive substances in the diabetic brain compared to untreated diabetic rats (P < 0.05). Morin also significantly decreased the level of inflammatory markers (TNFα, IL1β, IL-6) in the diabetic brain compared to untreated diabetic rats. Furthermore, the drug influenced an increase in the level of neurotrophic factors (BDNF, NGF and IGF-1) in the diabetic brain compared to untreated diabetic rats (P < 0.05). Thus, our results indicate a beneficial effect of morin by decreasing oxidative stress, inflammation and increasing the neurotrophic support in the diabetic brain, which may ameliorate diabetic encephalopathy.
Literature
1.
go back to reference Ola MS, Nawaz MI, Siddiquei MM et al (2012) Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complicat 26:56–64PubMedCrossRef Ola MS, Nawaz MI, Siddiquei MM et al (2012) Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complicat 26:56–64PubMedCrossRef
3.
go back to reference Sun YM, Su Y, Li J et al (2013) Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem Biophys Res Commun 433:359–361PubMedCrossRef Sun YM, Su Y, Li J et al (2013) Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem Biophys Res Commun 433:359–361PubMedCrossRef
4.
go back to reference Navaratna D, Guo SZ, Hayakawa K et al (2011) Decreased cerebrovascular brain-derived neurotrophic factor-mediated neuroprotection in the diabetic brain. Diabetes 60:1789–1796PubMedCentralPubMedCrossRef Navaratna D, Guo SZ, Hayakawa K et al (2011) Decreased cerebrovascular brain-derived neurotrophic factor-mediated neuroprotection in the diabetic brain. Diabetes 60:1789–1796PubMedCentralPubMedCrossRef
5.
go back to reference Francis GJ, Martinez JA, Liu WQ et al (2008) Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain 131:3311–3334PubMedCrossRef Francis GJ, Martinez JA, Liu WQ et al (2008) Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain 131:3311–3334PubMedCrossRef
6.
go back to reference Reagan LP, Magariños AM, McEwen BS (2000) Neurological changes induced by stress in streptozotocin diabetic rats. Nature 404:787–790CrossRef Reagan LP, Magariños AM, McEwen BS (2000) Neurological changes induced by stress in streptozotocin diabetic rats. Nature 404:787–790CrossRef
7.
go back to reference Acar A, Akil E, Alp H et al (2012) Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats. Int J Neurosci 122:367–372PubMedCrossRef Acar A, Akil E, Alp H et al (2012) Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats. Int J Neurosci 122:367–372PubMedCrossRef
8.
go back to reference Prabhakar O (2013) Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 386(8):705–710PubMedCrossRef Prabhakar O (2013) Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol 386(8):705–710PubMedCrossRef
9.
go back to reference Li ZG, Zhang W, Sima AA (2005) The role of impaired insulin/IGF action in primary diabetic encephalopathy. Brain Res 1037:12–24PubMedCrossRef Li ZG, Zhang W, Sima AA (2005) The role of impaired insulin/IGF action in primary diabetic encephalopathy. Brain Res 1037:12–24PubMedCrossRef
10.
go back to reference Tirassa P, Maccarone M, Florenzano F et al (2013) Vascular and neuronal protection induced by the ocular administration of nerve growth factor in diabetic-induced rat encephalopathy. CNS Neurosci Ther 19:307–318PubMedCrossRef Tirassa P, Maccarone M, Florenzano F et al (2013) Vascular and neuronal protection induced by the ocular administration of nerve growth factor in diabetic-induced rat encephalopathy. CNS Neurosci Ther 19:307–318PubMedCrossRef
11.
go back to reference Nitta A, Murai R, Suzuki N et al (2002) Diabetic neuropathies in brain are induced by deficiency of BDNF. Neurotoxicol Teratol 24:695–701PubMedCrossRef Nitta A, Murai R, Suzuki N et al (2002) Diabetic neuropathies in brain are induced by deficiency of BDNF. Neurotoxicol Teratol 24:695–701PubMedCrossRef
12.
go back to reference Sposato V, Manni L, Chaldakov GN et al (2007) Streptozotocin-induced diabetes is associated with changes in NGF levels in pancreas and brain. Arch Ital Biol 145:87–97PubMed Sposato V, Manni L, Chaldakov GN et al (2007) Streptozotocin-induced diabetes is associated with changes in NGF levels in pancreas and brain. Arch Ital Biol 145:87–97PubMed
13.
go back to reference Abuohashish HM, Al-Rejaie SS, Al-Hosaini KA et al (2013) Alleviating effects of morin against experimentally-induced diabetic osteopenia. Diabetol Metab Syndr 5:5PubMedCentralPubMedCrossRef Abuohashish HM, Al-Rejaie SS, Al-Hosaini KA et al (2013) Alleviating effects of morin against experimentally-induced diabetic osteopenia. Diabetol Metab Syndr 5:5PubMedCentralPubMedCrossRef
14.
go back to reference Prahalathan P, Kumar S, Raja B (2012) Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: a biochemical and histopathological evaluation. Metabolism 61:1087–1099PubMedCrossRef Prahalathan P, Kumar S, Raja B (2012) Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: a biochemical and histopathological evaluation. Metabolism 61:1087–1099PubMedCrossRef
15.
go back to reference Fang SH, Hou YC, Chang WC et al (2003) Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci 74:743–756PubMedCrossRef Fang SH, Hou YC, Chang WC et al (2003) Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci 74:743–756PubMedCrossRef
16.
go back to reference Aleisa AM, Al-Rejaie SS, Abuohashish HM et al (2013) Nephro-protective role of morin against experimentally induced diabetic retinopathy. Digest J Nanomaterials Biostructureol 8:395–401 Aleisa AM, Al-Rejaie SS, Abuohashish HM et al (2013) Nephro-protective role of morin against experimentally induced diabetic retinopathy. Digest J Nanomaterials Biostructureol 8:395–401
17.
go back to reference Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205PubMedCrossRef Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205PubMedCrossRef
18.
go back to reference Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195PubMedCrossRef Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195PubMedCrossRef
19.
go back to reference Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 673–684 Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 673–684
20.
go back to reference Huang M, Gao L, Yang L et al (2012) Abnormalities in the brain of streptozotocin-induced type 1 diabetic rats revealed by diffusion tensor imaging. Neuroimage Clin 1:57–65PubMedCentralPubMedCrossRef Huang M, Gao L, Yang L et al (2012) Abnormalities in the brain of streptozotocin-induced type 1 diabetic rats revealed by diffusion tensor imaging. Neuroimage Clin 1:57–65PubMedCentralPubMedCrossRef
21.
go back to reference Ola MS, Ahmed MM, Abuohashish HM et al (2013) Telmisartan ameliorates neurotrophic support and oxidative stress in the retina of streptozotocin-induced diabetic rats. Neurochem Res 38:1572–1579PubMedCrossRef Ola MS, Ahmed MM, Abuohashish HM et al (2013) Telmisartan ameliorates neurotrophic support and oxidative stress in the retina of streptozotocin-induced diabetic rats. Neurochem Res 38:1572–1579PubMedCrossRef
22.
go back to reference Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 17:97CrossRef Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 17:97CrossRef
23.
go back to reference Chen WP, Wang YL, Tang JL et al (2012) Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Int Immunopharmacol 12:447–452PubMedCrossRef Chen WP, Wang YL, Tang JL et al (2012) Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Int Immunopharmacol 12:447–452PubMedCrossRef
24.
go back to reference Manna SK, Aggarwal RS, Sethi G et al (2007) Morin (3,5,7,2′,4′-pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res 13:2290–2297PubMedCentralPubMedCrossRef Manna SK, Aggarwal RS, Sethi G et al (2007) Morin (3,5,7,2′,4′-pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res 13:2290–2297PubMedCentralPubMedCrossRef
25.
go back to reference Li R, Huang YG, Fang D et al (2004) (−)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 78:723–731PubMedCrossRef Li R, Huang YG, Fang D et al (2004) (−)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 78:723–731PubMedCrossRef
26.
go back to reference Xu SL, Bi CW, Choi RC et al (2013) Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor. Evid Based Complement Alternat Med 2013:127075PubMedCentralPubMed Xu SL, Bi CW, Choi RC et al (2013) Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor. Evid Based Complement Alternat Med 2013:127075PubMedCentralPubMed
27.
go back to reference De Nicoló S, Tarani L, Ceccanti M et al (2013) Effects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse brain. Nutrition 29:681–687PubMedCrossRef De Nicoló S, Tarani L, Ceccanti M et al (2013) Effects of olive polyphenols administration on nerve growth factor and brain-derived neurotrophic factor in the mouse brain. Nutrition 29:681–687PubMedCrossRef
Metadata
Title
Flavonoid, morin inhibits oxidative stress, inflammation and enhances neurotrophic support in the brain of streptozotocin-induced diabetic rats
Authors
Mohammad S. Ola
Abdulaziz M. Aleisa
Salim S. Al-Rejaie
Hatem M. Abuohashish
Mihir Y. Parmar
Abdullah S. Alhomida
Mohammed M. Ahmed
Publication date
01-07-2014
Publisher
Springer Milan
Published in
Neurological Sciences / Issue 7/2014
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-014-1628-5

Other articles of this Issue 7/2014

Neurological Sciences 7/2014 Go to the issue