Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies.
Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius L. markedly extended the coagulation time in mice and exhibited a significant antithrombotic effect in rats. The present study was conducted to demonstrate further its neuroprotective effects on cerebral ischemic injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY) rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological deficit scores followed by the treatment with a single dose of HSYA. Furthermore, the infarction area of the brain was assessed in the brain slices. In vitro, the effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage. The results in vivo showed that sublingular vein injection of HSYA at doses of 3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly decreasing neurological deficit scores and reducing the infarct area compared with the saline group, HSYA at a dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg. Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a neuroprotective effect, however, with no significant difference when compared with the saline group. Results in vitro showed that HSYA significantly inhibited neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on glutamate-mediated neuron injury was much better than that of HSYA on NaCN-induced neuron damage. All these findings suggest that HSYA might act as a potential neuroprotective agent useful in the treatment in focal cerebral ischemia. Abbreviations. HSYA:hydroxysafflor yellow A TTC:2,3,5-triphenyltetrazolium chloride MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide DMEM:Dulbecco's modified Eagle medium FCS:Fetal calf serum MCAO:middle cerebral artery occlusion ECA:external carotid artery ICA:internal carotid artery LDH:lactate dehydrogenase NMDA: N-methyl- D-aspartate
Zhu
Haibo
H
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Wang
Zhenhua
Z
Ma
Chengjun
C
Tian
Jingwei
J
Fu
Fenghua
F
Li
Changling
C
Guo
Dean
D
Roeder
E
E
Liu
Ke
K
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control; D031187:Carthamus tinctorius; D002599:Chalcone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011809:Quinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011921:Rats, Inbred WKY; D012966:Sodium Cyanide
D018696:Neuroprotective Agents; D010936:Plant Extracts; D011809:Quinones; C085278:hydroxysafflor yellow A; D018698:Glutamic Acid; D002599:Chalcone; D012966:Sodium Cyanide