title: Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction.
abstract: OBJECTIVE
  The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rg1 is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rg1 can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction.
  
  
  METHODS
  We investigated the effects of ginsenoside Rg1 at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naïve and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein (APP) (H4-APP cells). For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore (mPTP) and adenosine-5'-triphosphate (ATP) levels. We employed Western blot analysis, chemiluminescence, and flowcytometry.
  
  
  RESULTS
  Here we show that pretreatment with 50 µmol/L ginsenoside Rg1 for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 µmol/L ginsenoside Rg1 for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naïve and H4-APP cells.
  
  
  CONCLUSIONS
  These data suggest that ginsenoside Rg1 may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rg1 in preventing and treating isoflurane-induced neurotoxicity.
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Hui Hui
authors.initials: HH
authors.lastname: Miao
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Guan Nan
authors.initials: GN
authors.lastname: Ding
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Fang Xiao
authors.initials: FX
authors.lastname: Hong
authors.affiliation: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard MedicalSchool, Charlestown, MA 02129-2060, USA.
authors.forename: Zhong Cong
authors.initials: ZC
authors.lastname: Xie
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tian
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D036145:Ginsenosides; D015759:Ionomycin; D007530:Isoflurane; C505410:Casp3 protein, rat; D053148:Caspase 3; C035054:ginsenoside Rg1
keywords: Ginsenoside Rg1; Isoflurane; Mitochondrial dysfunction; Neurotoxicity