title: Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival.
abstract: Valproic acid (VPA) is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC) activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella asiatica. Our previous study has shown that Asiatic acid improves working spatial memory and increases cell proliferation in the sub granular zone of the hippocampal dentate gyrus. In the present study we investigate the effects of Asiatic acid in preventing the memory and cellular effects of VPA. Male Spraque-Dawley rats were orally administered Asiatic acid (30 mg/kg/day) for 28 days, while VPA-treated animals received injections of VPA (300 mg/kg) twice a day from Day 15 to Day 28 for 14 days. Spatial memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival was quantified by immuostaining for Ki-67 and Bromodeoxyuridine (BrdU), respectively. The results showed that VPA-treated animals were unable to discriminate between objects in familiar and novel locations. Moreover, VPA significantly reduced numbers of Ki-67 and BrdU positive cells. These results indicate that VPA treatment caused impairments of spatial working memory, cell proliferation and survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). However, these abnormalities were restored to control levels by co-treatment with Asiatic acid. These data demonstrate that Asiatic acid could prevent the spatial memory and neurogenesis impairments caused by VPA.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. jariya@kku.ac.th.|Center for Research and Development of Herbal Health Products, Khon Kaen University, Khon Kaen 40002, Thailand. jariya@kku.ac.th.|Neuroscience Research and Development Group, Khon Kaen University, Khon Kaen 40002, Thailand. jariya@kku.ac.th.
authors.forename: Jariya
authors.initials: J
authors.lastname: Umka Welbat
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. dek_saba@hotmail.com.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Sirichoat
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. cwunnee@kku.ac.th.
authors.forename: Wunnee
authors.initials: W
authors.lastname: Chaijaroonkhanarak
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. parpra@kku.ac.th.
authors.forename: Parichat
authors.initials: P
authors.lastname: Prachaney
authors.affiliation: Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. wankun@kku.ac.th.|Center for Research and Development of Herbal Health Products, Khon Kaen University, Khon Kaen 40002, Thailand. wankun@kku.ac.th.
authors.forename: Wanassanun
authors.initials: W
authors.lastname: Pannangrong
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. ppoung@kku.ac.th.
authors.forename: Poungrat
authors.initials: P
authors.lastname: Pakdeechote
authors.affiliation: Center for Research and Development of Herbal Health Products, Khon Kaen University, Khon Kaen 40002, Thailand. bungorn@kku.ac.th.
authors.forename: Bungorn
authors.initials: B
authors.lastname: Sripanidkulchai
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, Nottingham University, Nottingham NG7 2UH, UK. peter.wigmore@nottingham.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Wigmore
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology*; D007150:Immunohistochemistry; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D053978:Pentacyclic Triterpenes; D014635:Valproic Acid; C017032:asiatic acid
keywords: Asiatic acid; neurogenesis; spatial memory; valproic acid