title: Ginkgo biloba L. attenuates spontaneous recurrent seizures and associated neurological conditions in lithium-pilocarpine rat model of temporal lobe epilepsy through inhibition of mammalian target of rapamycin pathway hyperactivation.
abstract: BACKGROUND
  Ginkgo biloba L. (Ginkgoaceae) has been widely used in traditional medicine for variety of neurological conditions particularly behavioral and memory impairments.
  
  
  OBJECTIVE
  The present study was envisaged to explore the effect of a standardized fraction of Ginkgo biloba leaves (GBbf) in rat model of lithium-pilocarpine induced spontaneous recurrent seizures, and associated behavioral impairments and cognitive deficit.
  
  
  METHODS
  Rats showing appearance of spontaneous recurrent seizures following lithium pilocarpine (LiPc)-induced status epilepticus (SE) were treated with different doses of GBbf or vehicle for subsequent 4 weeks. The severity of seizures and aggression in rats were scored following treatment with GBbf. Further, open field, forced swim, novel object recognition and Morris water maze tests were conducted. Histopathological, protein levels and gene expression studies were performed in the isolated brains.
  
  
  RESULTS
  Treatment with GBbf reduced seizure severity score and aggression in epileptic animals. Improved spatial cognitive functions and recognition memory, along with reduction in anxiety-like behavior were also observed in the treated animals. Histopathological examination by Nissl staining showed reduction in neuronal damage in the hippocampal pyramidal layer. The dentate gyrus and Cornu Ammonis 3 regions of the hippocampus showed reduction in mossy fiber sprouting. GBbf treatment attenuated ribosomal S6 and pS6 proteins, and hippocampal mTOR, Rps6 and Rps6kb1 mRNA levels.
  
  
  CONCLUSIONS
  The results of present study concluded that GBbf treatment suppressed lithium-pilocarpine induced spontaneous recurrent seizures severity and incidence with improved cognitive functions, reduced anxiety-like behavior and aggression. The effect was found to be due to inhibition of mTOR pathway hyperactivation linked with recurrent seizures.
authors.affiliation: Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India.
authors.forename: Arindam Ghosh
authors.initials: AG
authors.lastname: Mazumder
authors.affiliation: Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Patial
authors.affiliation: Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India. Electronic address: dsinghpharmacology@gmail.com.
authors.forename: Damanpreet
authors.initials: D
authors.lastname: Singh
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D020441:Ginkgo biloba; D018021:Lithium Chloride; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008517:Phytotherapy; D010862:Pilocarpine; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D038601:Ribosomal Protein S6 / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D010862:Pilocarpine; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D018021:Lithium Chloride
keywords: Epilepsy; Flavonoid glycosides; Ginkgo biloba L. (Ginkgoaceae); Hippocampus mossy fibers; Ribosomal S6 protein