title: Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia.
abstract: Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate- or beta-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.
authors.affiliation: Division of Cerebrovascular Diseases and Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Rajanikant G
authors.initials: RG
authors.lastname: Krishnamurthy
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Senut
authors.forename: Daniel
authors.initials: D
authors.lastname: Zemke
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Min
authors.forename: Mark B
authors.initials: MB
authors.lastname: Frenkel
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Greenberg
authors.forename: Seong-Woon
authors.initials: SW
authors.lastname: Yu
authors.forename: Nick
authors.initials: N
authors.lastname: Ahn
authors.forename: John
authors.initials: J
authors.lastname: Goudreau
authors.forename: Mounzer
authors.initials: M
authors.lastname: Kassab
authors.forename: Kiran S
authors.initials: KS
authors.lastname: Panickar
authors.forename: Arshad
authors.initials: A
authors.lastname: Majid
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D007074:Immunoglobulin G / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D053978:Pentacyclic Triterpenes; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014315:Triterpenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007074:Immunoglobulin G; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D045304:Cytochromes c; C017032:asiatic acid; D005947:Glucose