title: Combination of Zizyphus jujuba and silymarin showed better neuroprotective effect as compared to single agent in MCAo-induced focal cerebral ischemia in rats.
abstract: BACKGROUND
  Traditionally, Zizyphus jujuba is used for anticonvulsant, hypnotic-sedative, anxiolytic, tranquilizer, antioxidant and anti-inflammatory properties. Likewise silymarin is popularly used for its potent antioxidant and hepatoprotective effects. Stroke being a multifactorial disease with unsatisfactory treatment outcomes, necessitates development of multimodal therapeutic interventions. Thus, we evaluated the therapeutic benefits of herbal combination of Z. jujuba and silymarin in a focal cerebral ischemia model.
  
  
  OBJECTIVE
  To evaluate the neuroprotective potential of hydroalcoholic extract of Z. jujuba (HEZJ) fruit and silymarin alone and in combination in middle cerebral artery occlusion (MCAo) model of focal cerebral ischemia in rats.
  
  
  METHODS
  Male Wistar rats were pretreated with HEZJ (100, 250 and 500mg/kg, p.o.) or silymarin (250mg/kg, p.o.) for 3 days prior to induction of MCAo. Neurological deficit score, motor impairment and cerebral infarction were assessed 24h following MCAo. HEZJ (250mg/kg) co-administered with silymarin (250mg/kg) for 3 days prior to induction of MCAo was also evaluated for above parameters and oxidative stress. Malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) levels in the cortex, striatum and hippocampal brain regions were estimated 24h post MCAo.
  
  
  RESULTS
  Pretreatment with HEZJ and silymarin reduced the neurological deficit score, motor impairment and cerebral infarction volume. HEZJ and silymarin pretreatment also ameliorated the oxidative stress in different brain regions, which was evident from increased SOD levels, decreased MDA and NO levels as compared to MCAo control rats. Interestingly neuroprotective efficacy was potentiated by pretreatment with HEZJ and silymarin combination.
  
  
  CONCLUSIONS
  Pretreatment with HEZJ and silymarin combination was observed to have better neuroprotection mediated via amelioration of oxidative stress in the focal cerebral ischemia model.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: yk.ykgupta@gmail.com.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D031957:Ziziphus / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D018696:Neuroprotective Agents; D012838:Silymarin; D008315:Malondialdehyde; D013482:Superoxide Dismutase
keywords: Focal cerebral ischemia; MCAo; Neuroprotection; Oxidative stress; Silymarin; Zizyphus jujuba