title: Herba Cistanches stimulates cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration in H9c2 cardiomyocytes.
abstract: BACKGROUND
  Earlier findings demonstrated that pretreatment of Herba Cistanches [the dried whole plant of Cistanche deserticola Y.C. Ma (Orobanchaceae)], a "Yang-invigorating" Chinese tonic herb, stimulated the ATP-generation capacity (ATP-GC) in mitochondria isolated from rat heart ex vivo. The enhancement of mitochondrial ATP-GC by Herba Cistanches was associated with induction of glutathione antioxidant status and protection against ischemia/reperfusion (I/R) injury in rat hearts.
  
  
  OBJECTIVE
  This study investigated the relationship between enhancements in mitochondrial ATP-GC and glutathione antioxidant status in H9c2 cardiomyocytes using a semipurified fraction of Herba Cistanches (HCF1).
  
  
  METHODS
  HCF1 (10-300 ng/mL) was tested for its effects on mitochondrial ATP generation, glutathione antioxidant status and protection against oxidant injury in H9c2 cardiomyocytes and rat hearts.
  
  
  CONCLUSIONS
  HCF1 at 30 ng/mL increased mitochondrial ATP-GC and ADP-stimulated state 3 respiration (by 50 and 100%, respectively) in H9c2 cardiomyocytes. The stimulation of mitochondrial respiration was associated with the induction of mitochondrial uncoupling (27%) and enhancement of cellular glutathione redox cycling as well as protection against hypoxia/reoxygenation (hypox/reoxy)-induced apoptosis (by 60%). While HCF1 treatment increased reactive oxygen species generation from mitochondrial respiration in H9c2 cardiomyocytes, pretreatment with antioxidants (DMTU) abrogated the HCF1-induced cellular responses and the associated cytoprotective effect. HCF1 pretreatment (1.14 and 3.41 mg/kg × 14) also protected against myocardial I/R injury in rats (by 13 and 32%), presumably mediated by the induction of glutathione antioxidant response.
  
  
  CONCLUSIONS
  The long-term intake of HCF1 may offer a prospect for the prevention of ischemic heart disease.
authors.affiliation: Division of Life Science, Hong Kong University of Science & Technology Clear Water Bay, Hong Kong SAR, China.
authors.forename: Hoi Shan
authors.initials: HS
authors.lastname: Wong
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D031671:Cistanche / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D005978:Glutathione