title: Combination of total Astragalus extract and total Panax notoginseng saponins strengthened the protective effects on brain damage through improving energy metabolism and inhibiting apoptosis after cerebral ischemia-reperfusion in mice.
abstract: OBJECTIVE
  To explore the effects and molecular mechanisms of the combination between total Astragalus extract (TAE) and total Panax notoginseng saponins (TPNS) against cerebral ischemia-reperfusion injury.
  
  
  METHODS
  C57BL/6 mice were randomly divided into sham-operated group, model group, TAE (110 mg/kg) group, TPNS (115 mg/kg) group, TAE-TPNS combination group and Edaravone (4 mg/kg) group, treated for 4 days, then, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery (CCA) ligation for 20 min followed by reperfusion for 1 and 24 h.
  
  
  RESULTS
  TPNS could increase adenosine triphosphate (ATP) level, TAE and TAE-TPNS combination increased ATP, adenosine diphosphate (ADP) contents and Na+-K+-ATPase activity, and the effects of TAE-TPNS combination were stronger than those of TAE or TPNS alone after reperfusion for 1 h. After reperfusion for 24 h, TAE, TPNS and TAE-TPNS combination significantly increased neurocyte survival rate and decreased the apoptosis rate as well as down-regulated the expression of phosphorylated c-June N-terminal kinase1/2 (p-JNK1/2), cytochrome C (Cyt C), cysteine aspartic acid-specific protease (Caspase)-9 and Caspase-3. Furthermore, the effects in TAE-TPNS combination were better than those in TAE or TPNS alone.
  
  
  CONCLUSIONS
  The combination of TAE 110 mg/kg and TPNS 115 mg/kg could strengthen protective effects on cerebral ischemia injury, the mechanism underlying might be related to improving jointly the early energy metabolism, and relieving the delayed apoptosis via inhibiting the mitochondrial apoptosis pathway of JNK signal transduction.
authors: Key Laboratory of Hunan Universities for Cell Biology and Molecular Techniques, Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410007, China.
authors: Xiao-Ping
authors: XP
authors: Huang
authors: Key Laboratory of Hunan Universities for Cell Biology and Molecular Techniques, Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410007, China.
authors: Hua
authors: H
authors: Tan
authors: Department of Histology and Embryology, Hunan University of Chinese Medicine, Changsha, 410208, China.
authors: Bei-Yang
authors: BY
authors: Chen
authors: Key Laboratory of Hunan Universities for Cell Biology and Molecular Techniques, Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410007, China. dchangq@sohu.com.
authors: Chang-Qing
authors: CQ
authors: Deng
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027883:Astragalus Plant / Q000737:chemistry*; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053723:Panax notoginseng / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; D012503:Saponins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D000254:Sodium-Potassium-Exchanging ATPase
keywords: C-Jun N-terminal kinase signal transduction; Chinese medicine; cerebral ischemia-reperfusion; combination; energy metabolism; mitochondrial apoptosis pathway; total Astragalus extract; total Panax notoginseng saponins