Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis
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摘要
Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis,using Complete Freund's Adjuvant(CFA) emulsion containing myelin oligodendrocyte glycoprotein(35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.
Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis,using Complete Freund's Adjuvant(CFA) emulsion containing myelin oligodendrocyte glycoprotein(35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.
Hydroxycitric acid(HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis,using Complete Freund's Adjuvant(CFA) emulsion containing myelin oligodendrocyte glycoprotein(35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.
引文
Afraei S,Azizi G,Zargar SJ,Sedaghat R,Mirshafiey A(2015)New therapeutic approach by G2013 in experimental model of multiple sclerosis.Acta Neurol Belg 115:259-266.
Amin KA,Kamel HH,Abd Eltawab MA(2011a)The relation of high fat diet,metabolic disturbances and brain oxidative dysfunction:modulation by hydroxy citric acid.Lipids Health Dis 10:74.
Amin KA,Kamel HH,Abd Eltawab MA(2011b)Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet.Lipids Health Dis 10:6.
Asghar M,Monjok E,Kouamou G,Ohia SE,Bagchi D,Lokhandwala MF(2007)Super Citri Max(HCA-SX)attenuates increases in oxidative stress,inflammation,insulin resistance,and body weight in developing obese Zucker rats.Mol Cell Biochem 304:93-99.
Azizi G,Mirshafiey A(2013)Imatinib mesylate:an innovation in treatment of autoimmune diseases.Recent Pat Inflamm Allergy Drug Discov 7:259-267.
Azizi G,Goudarzvand M,Afraei S,Sedaghat R,Mirshafiey A(2015)Therapeutic effects of dasatinib in mouse model of multiple sclerosis.Immunopharmacol Immunotoxicol 37:287-294.
Azizi G,Haidari MR,Khorramizadeh M,Naddafi F,Sadria R,Javanbakht MH,Sedaghat R,Tofighi Zavareh F,Mirshafiey A(2014)Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants.Iran J Allergy Asthma Immunol 13:198-206.
Beck J,Rondot P,Catinot L,Falcoff E,Kirchner H,Wietzerbin J(1988)Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis:do cytokines trigger off exacerbations?Acta Neurol Scand 78:318-323.
Clouatre DL,Preuss HG(2013)Hydroxycitric acid does not promote inflammation or liver toxicity.World J Gastroenterol 19:8160-8162.
dos Reis SB,de Oliveira CC,Acedo SC,Miranda DD,Ribeiro ML,Pedrazzoli J,Jr.,Gambero A(2009)Attenuation of colitis injury in rats using Garcinia cambogia extract.Phytother Res 23:324-329.
Fereidoni M,Sabouni F,Moghimi A,Hosseini S(2013)The effects of trypsin on rat brain astrocyte activation.Iran J Neurol 12:129-135.
Fonseca SG,Romao PR,Figueiredo F,Morais RH,Lima HC,Ferreira SH,Cunha FQ(2003)TNF-alpha mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis.Eur J Immunol 33:2297-2306.
Haghmorad D,Mahmoudi MB,Mahmoudi M,Rab SZ,Rastin M,Shegarfi H,Azizi G,Mirshafiey A(2014)Calcium intervention ameliorates experimental model of multiple sclerosis.Oman Med J 29:185-189.
Huitinga I,Ruuls SR,Jung S,Van Rooijen N,Hartung HP,Dijkstra CD(1995)Macrophages in T cell line-mediated,demyelinating,and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats.Clin Exp Immunol 100:344-351.
Jana M,Pahan K(2013)Down-regulation of myelin gene expression in human oligodendrocytes by nitric oxide:implications for demyelination in multiple sclerosis.J Clin Cell Immunol 4.
Kim JE,Jeon SM,Park KH,Lee WS,Jeong TS,Mc Gregor RA,Choi MS(2011)Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals:a randomized control trial.Nutr J 10:94.
Kim YJ,Kim KY,Kim MS,Lee JH,Lee KP,Park T(2008)A mixture of the aqueous extract of Garcinia cambogia,soy peptide and L:-carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet.Genes Nutr 2:353-358.
Kolodziejczyk J,Masullo M,Olas B,Piacente S,Wachowicz B(2009)Effects of garcinol and guttiferone K isolated from Garcinia cambogia on oxidative/nitrative modifications in blood platelets and plasma.Platelets 20:487-492.
Lopez-Diego RS,Weiner HL(2008)Novel therapeutic strategies for multiple sclerosis--a multifaceted adversary.Nat Rev Drug Discov7:909-925.
Lu F,Selak M,O’Connor J,Croul S,Lorenzana C,Butunoi C,Kalman B(2000)Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis.JNeurol Sci 177:95-103.
Lu XY,Zeng YY,Ye YX,Zhou YY,Mu JJ,Zhao XH(2009)Anti-inflammatory and immunosuppressive effect of phloretin.Yao Xue Xue Bao44:480-485.
Mahendran P,Vanisree AJ,Shyamala Devi CS(2002)The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in rats.Phytother Res 16:80-83.
Marquez F,Babio N,Bullo M,Salas-Salvado J(2012)Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans.Crit Rev Food Sci Nutr 52:585-594.
Masullo M,Menegazzi M,Di Micco S,Beffy P,Bifulco G,Dal Bosco M,Novelli M,Pizza C,Masiello P,Piacente S(2014)Direct interaction of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways.J Nat Prod 77:543-549.
Miller E,Wachowicz B,Majsterek I(2013)Advances in antioxidative therapy of multiple sclerosis.Curr Med Chem 20:4720-4730.
Mirshafiey A,Ghalamfarsa G,Asghari B,Azizi G(2014a)Receptor tyrosine kinase and tyrosine kinase inhibitors:new hope for success in multiple sclerosis therapy.Innov Clin Neurosci 11:23-36.
Mirshafiey A,Asghari B,Ghalamfarsa G,Jadidi-Niaragh F,Azizi G(2014b)The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis.Sultan Qaboos Univ Med J 14:e13-25.
Moriya M,Nakatsuji Y,Miyamoto K,Okuno T,Kinoshita M,Kumanogoh A,Kusunoki S,Sakoda S(2008)Edaravone,a free radical scavenger,ameliorates experimental autoimmune encephalomyelitis.Neurosci Lett 440:323-326.
Murphy AC,Lalor SJ,Lynch MA,Mills KH(2010)Infiltration of Th1and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis.Brain Behav Immun 24:641-651.
Murphy S(2000)Production of nitric oxide by glial cells:regulation and potential roles in the CNS.Glia 29:1-13.
Naddafi F,Reza Haidari M,Azizi G,Sedaghat R,Mirshafiey A(2013)Novel therapeutic approach by nicotine in experimental model of multiple sclerosis.Innov Clin Neurosci 10:20-25.
Peiris M,Monteith GR,Roberts-Thomson SJ,Cabot PJ(2007)A model of experimental autoimmune encephalomyelitis(EAE)in C57BL/6mice for the characterisation of intervention therapies.J Neurosci Methods 163:245-254.
Riccio P,Rossano R,Liuzzi GM(2011)May diet and dietary supplements improve the wellness of multiple sclerosis patients?A molecular approach.Autoimmune Dis 2010:249842.
Satoh K(1978)Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.Clin Chim Acta 90:37-43.
Shin T,Tanuma N,Kim S,Jin J,Moon C,Kim K,Kohyama K,Matsumoto Y,Hyun B(1998)An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats.J Neuroimmunol 92:133-138.
Smith KJ,Lassmann H(2002)The role of nitric oxide in multiple sclerosis.Lancet Neurol 1:232-241.
Sripradha R,Magadi SG(2015)Efficacy of garcinia cambogia on body weight,inflammation and glucose tolerance in high fat fed male wistar rats.J Clin Diagn Res 9:BF01-04.
Sriram S(2011)Role of glial cells in innate immunity and their role in CNS demyelination.J Neuroimmunol 239:13-20.
Steinman L(2001)Multiple sclerosis:a two-stage disease.Nat Immunol2:762-764.
Taupin V,Renno T,Bourbonniere L,Peterson AC,Rodriguez M,Owens T(1997)Increased severity of experimental autoimmune encephalomyelitis,chronic macrophage/microglial reactivity,and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system.Eur J Immunol 27:905-913.
Amin KA,Kamel HH,Abd Eltawab MA(2011a)The relation of high fat diet,metabolic disturbances and brain oxidative dysfunction:modulation by hydroxy citric acid.Lipids Health Dis 10:74.
Amin KA,Kamel HH,Abd Eltawab MA(2011b)Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet.Lipids Health Dis 10:6.
Asghar M,Monjok E,Kouamou G,Ohia SE,Bagchi D,Lokhandwala MF(2007)Super Citri Max(HCA-SX)attenuates increases in oxidative stress,inflammation,insulin resistance,and body weight in developing obese Zucker rats.Mol Cell Biochem 304:93-99.
Azizi G,Mirshafiey A(2013)Imatinib mesylate:an innovation in treatment of autoimmune diseases.Recent Pat Inflamm Allergy Drug Discov 7:259-267.
Azizi G,Goudarzvand M,Afraei S,Sedaghat R,Mirshafiey A(2015)Therapeutic effects of dasatinib in mouse model of multiple sclerosis.Immunopharmacol Immunotoxicol 37:287-294.
Azizi G,Haidari MR,Khorramizadeh M,Naddafi F,Sadria R,Javanbakht MH,Sedaghat R,Tofighi Zavareh F,Mirshafiey A(2014)Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants.Iran J Allergy Asthma Immunol 13:198-206.
Beck J,Rondot P,Catinot L,Falcoff E,Kirchner H,Wietzerbin J(1988)Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis:do cytokines trigger off exacerbations?Acta Neurol Scand 78:318-323.
Clouatre DL,Preuss HG(2013)Hydroxycitric acid does not promote inflammation or liver toxicity.World J Gastroenterol 19:8160-8162.
dos Reis SB,de Oliveira CC,Acedo SC,Miranda DD,Ribeiro ML,Pedrazzoli J,Jr.,Gambero A(2009)Attenuation of colitis injury in rats using Garcinia cambogia extract.Phytother Res 23:324-329.
Fereidoni M,Sabouni F,Moghimi A,Hosseini S(2013)The effects of trypsin on rat brain astrocyte activation.Iran J Neurol 12:129-135.
Fonseca SG,Romao PR,Figueiredo F,Morais RH,Lima HC,Ferreira SH,Cunha FQ(2003)TNF-alpha mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis.Eur J Immunol 33:2297-2306.
Haghmorad D,Mahmoudi MB,Mahmoudi M,Rab SZ,Rastin M,Shegarfi H,Azizi G,Mirshafiey A(2014)Calcium intervention ameliorates experimental model of multiple sclerosis.Oman Med J 29:185-189.
Huitinga I,Ruuls SR,Jung S,Van Rooijen N,Hartung HP,Dijkstra CD(1995)Macrophages in T cell line-mediated,demyelinating,and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats.Clin Exp Immunol 100:344-351.
Jana M,Pahan K(2013)Down-regulation of myelin gene expression in human oligodendrocytes by nitric oxide:implications for demyelination in multiple sclerosis.J Clin Cell Immunol 4.
Kim JE,Jeon SM,Park KH,Lee WS,Jeong TS,Mc Gregor RA,Choi MS(2011)Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals:a randomized control trial.Nutr J 10:94.
Kim YJ,Kim KY,Kim MS,Lee JH,Lee KP,Park T(2008)A mixture of the aqueous extract of Garcinia cambogia,soy peptide and L:-carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet.Genes Nutr 2:353-358.
Kolodziejczyk J,Masullo M,Olas B,Piacente S,Wachowicz B(2009)Effects of garcinol and guttiferone K isolated from Garcinia cambogia on oxidative/nitrative modifications in blood platelets and plasma.Platelets 20:487-492.
Lopez-Diego RS,Weiner HL(2008)Novel therapeutic strategies for multiple sclerosis--a multifaceted adversary.Nat Rev Drug Discov7:909-925.
Lu F,Selak M,O’Connor J,Croul S,Lorenzana C,Butunoi C,Kalman B(2000)Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis.JNeurol Sci 177:95-103.
Lu XY,Zeng YY,Ye YX,Zhou YY,Mu JJ,Zhao XH(2009)Anti-inflammatory and immunosuppressive effect of phloretin.Yao Xue Xue Bao44:480-485.
Mahendran P,Vanisree AJ,Shyamala Devi CS(2002)The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in rats.Phytother Res 16:80-83.
Marquez F,Babio N,Bullo M,Salas-Salvado J(2012)Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans.Crit Rev Food Sci Nutr 52:585-594.
Masullo M,Menegazzi M,Di Micco S,Beffy P,Bifulco G,Dal Bosco M,Novelli M,Pizza C,Masiello P,Piacente S(2014)Direct interaction of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways.J Nat Prod 77:543-549.
Miller E,Wachowicz B,Majsterek I(2013)Advances in antioxidative therapy of multiple sclerosis.Curr Med Chem 20:4720-4730.
Mirshafiey A,Ghalamfarsa G,Asghari B,Azizi G(2014a)Receptor tyrosine kinase and tyrosine kinase inhibitors:new hope for success in multiple sclerosis therapy.Innov Clin Neurosci 11:23-36.
Mirshafiey A,Asghari B,Ghalamfarsa G,Jadidi-Niaragh F,Azizi G(2014b)The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis.Sultan Qaboos Univ Med J 14:e13-25.
Moriya M,Nakatsuji Y,Miyamoto K,Okuno T,Kinoshita M,Kumanogoh A,Kusunoki S,Sakoda S(2008)Edaravone,a free radical scavenger,ameliorates experimental autoimmune encephalomyelitis.Neurosci Lett 440:323-326.
Murphy AC,Lalor SJ,Lynch MA,Mills KH(2010)Infiltration of Th1and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis.Brain Behav Immun 24:641-651.
Murphy S(2000)Production of nitric oxide by glial cells:regulation and potential roles in the CNS.Glia 29:1-13.
Naddafi F,Reza Haidari M,Azizi G,Sedaghat R,Mirshafiey A(2013)Novel therapeutic approach by nicotine in experimental model of multiple sclerosis.Innov Clin Neurosci 10:20-25.
Peiris M,Monteith GR,Roberts-Thomson SJ,Cabot PJ(2007)A model of experimental autoimmune encephalomyelitis(EAE)in C57BL/6mice for the characterisation of intervention therapies.J Neurosci Methods 163:245-254.
Riccio P,Rossano R,Liuzzi GM(2011)May diet and dietary supplements improve the wellness of multiple sclerosis patients?A molecular approach.Autoimmune Dis 2010:249842.
Satoh K(1978)Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.Clin Chim Acta 90:37-43.
Shin T,Tanuma N,Kim S,Jin J,Moon C,Kim K,Kohyama K,Matsumoto Y,Hyun B(1998)An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats.J Neuroimmunol 92:133-138.
Smith KJ,Lassmann H(2002)The role of nitric oxide in multiple sclerosis.Lancet Neurol 1:232-241.
Sripradha R,Magadi SG(2015)Efficacy of garcinia cambogia on body weight,inflammation and glucose tolerance in high fat fed male wistar rats.J Clin Diagn Res 9:BF01-04.
Sriram S(2011)Role of glial cells in innate immunity and their role in CNS demyelination.J Neuroimmunol 239:13-20.
Steinman L(2001)Multiple sclerosis:a two-stage disease.Nat Immunol2:762-764.
Taupin V,Renno T,Bourbonniere L,Peterson AC,Rodriguez M,Owens T(1997)Increased severity of experimental autoimmune encephalomyelitis,chronic macrophage/microglial reactivity,and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system.Eur J Immunol 27:905-913.