title: Expression pattern of NMDA receptors reveals antiepileptic potential of apigenin 8-C-glucoside and chlorogenic acid in pilocarpine induced epileptic mice.
abstract: The present study was aimed to evaluate the effect of apigenin 8-C-glucoside (Vitexin) and chlorogenic acid on epileptic mice induced by pilocarpine and explored its possible mechanisms. Intraperitonial administration of pilocarpine (85mg/kg) induced seizure in mice was assessed by behavior observations, which is significantly (p>0.05) reduced by apigenin 8-C-glucoside (AP8CG) (10mg/kg) and chlorogenic acid (CA) (5mg/kg), similar to diazepam. Seizure was accompanied by an imbalance in the levels of Gamma-aminobutyric acid (GABA) and glutamate in the pilocarpine administered group. Moreover, convulsion along with reduced acetylcholinesterase, increased monoamine oxidase and oxidative stress was observed in epileptic mice brain. AP8CG and CA significantly restored back to normal levels even at lower doses. Further, increased lipid peroxidation and nitrite content was also significantly attenuated by AP8CG and CA. However, CA was found to be more effective when compared to AP8CG. In addition, the mRNA expression of N-methyl-d-aspartate receptor (NMDAR), mGluR1 and mGlu5 was significantly (P≤0.05) inhibited by AP8CG and CA in a lower dose. The mRNA expression of GRIK1 did not differ significantly in any of the group and showed a similar pattern of expression. Our result shows that AP8CG and CA selectively inhibit NMDAR, mGluR1 and mGlu5 expression. Modification in the provoked NMDAR calcium response coupled with neuronal death. Hence, these findings underline that the polyphenolics, AP8CG and CA have exerted antiepileptic and neuroprotective activity by suppressing glutamate receptors.
authors.affiliation: Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: G Smilin Bell
authors.initials: GS
authors.lastname: Aseervatham
authors.affiliation: Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: U
authors.initials: U
authors.lastname: Suryakala
authors.affiliation: Central Inter-Disciplinary Research Facility, Mahatma Gandhi Medical College and Research Institute Campus, Pillayarkuppam, Puducherry 607 402, India.
authors.lastname: Doulethunisha
authors.affiliation: Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Department of Biotechnology, Anna University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: P Chandra
authors.initials: PC
authors.lastname: Bose
authors.affiliation: Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India. Electronic address: sudacoli@yahoo.com.
authors.forename: T
authors.initials: T
authors.lastname: Sivasudha
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D010862:Pilocarpine; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017392:Thiobarbituric Acid Reactive Substances; D010862:Pilocarpine; D002726:Chlorogenic Acid; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D047310:Apigenin; C032731:vitexin; D005978:Glutathione
keywords: Acetylcholinesterase; Antioxidant; Apigenin 8-C-glucoside; Chlorogenic acid; Epilepsy; NMDAR