title: Synergistic interaction between total glucosides and total flavonoids on chronic constriction injury induced neuropathic pain in rats.
abstract: BACKGROUND
  Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain.
  
  
  OBJECTIVE
  To investigate the synergistic potential of total glucosides of Paeoniae Radix (TGP) and total flavonoids of Glycyrrhizae Radix (TFL).
  
  
  METHODS
  Oral administration of TGP and TFL alone at the doses of 60,120 and 240 mg/kg or in combination were given only one time to the neuropathic pain rat induced by chronic constriction injury. Paw pressure and heat immersion tests were performed to assess degrees of mechanical allodynia and thermal hyperalgesia, respectively. Synergistic interactions between TGP and TFL were characterized using isobolographic analysis. Expressions of Sirt1 protein were detected by immunohistochemistry.
  
  
  CONCLUSIONS
  On day 14 after surgery, single oral administration of TGP and TFL both produced significant anti-allodynic and anti-hyperalgesic effects in dose-dependent and time-dependent manners. The ED(50) value of TGP was 249.4 ± 10.8 mg/kg while TFL was 871.4 ± 30.5 mg/kg. Isobolographic analysis revealed that the combination of TGP with TFL at the fixed ratios of 3:1 exerted the highest sub-additive (synergistic) interaction, of which the experimental ED(50) value was 95.1 ± 9.0 mg/kg. SGD could also downregulate Sirt1 protein expression, which was 4.2-fold higher than that of model rats in dorsal root ganglion.
  
  
  CONCLUSIONS
  Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.
authors: Zhejiang Chinese Medical Hospital, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
authors: Juan
authors: J
authors: Zhang
authors: Chen
authors: C
authors: Lv
authors: Hai-na
authors: HN
authors: Wang
authors: Yi
authors: Y
authors: Cao
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D029596:Paeonia / Q000737:chemistry; D058748:Pain Perception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000601:surgery; D056564:Sirtuin 1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D005960:Glucosides; C488368:Sirt1 protein, rat; D056564:Sirtuin 1