Neuroprotective effects of a standardized flavonoid extract from Diospyros kaki leaves.
BACKGROUND
Flavonoids, extracted from the leaves of Diospyros kaki, are the main therapeutic components of NaoXingQing (NXQ), a potent and patented Chinese herbal remedy widely used in China for the treatment of apoplexy syndrome.


OBJECTIVE
To investigate the neuroprotective effects of FLDK-P70, a standardized flavonoid extract, using in vivo rat models of both focal ischemia/reperfusion (I/R) injury induced by middle cerebral artery occlusion (MCAO) and on transient global brain ischemia induced by four-vessel occlusion (4-VO). We also aim to examine the effects of FLDK-P70 on glutamate-induced cell injury of hippocampal neurons as well as on hypoxia-induced injury of cortical neurons in primary cell culture.


RESULTS
Administration of FLDK-P70 for 12 days (40, 80 mg/kg body weight, p.o., 5 days before and 7 days after 4-VO) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. Similarly, administration of FLDK-P70 for 7 days (40, 80 mg/kg body weight, p.o., 3 days before and 4 days after MCAO) significantly reduced the lesion of the insulted brain hemisphere and improved the neurological behavior of rats. In primary rat hippocampal neuronal cultures, pretreatment with FLDK-P70 (5, 10 microg/ml) protected neurons from glutamate-induced excitotoxic neuronal death in a dose-dependent manner. In primary rat cerebral cortical neuronal culture, pretreatment with FLDK-P70 (25, 100 microg/ml) also reduced hypoxia-reoxygen induced neuronal death and apoptosis in a dose-dependent manner.


CONCLUSIONS
These in vivo and in vitro results suggest that FLDK-P70 significantly protects rats from MCAO and 4-VO ischemic injury in vivo and protects hippocampal neurons from glutamate-induced excitotoxic injury as well as cortical neurons from hypoxia-induced injury in vitro. The mechanisms of these effects may be due to the antioxidative activity of the flavonoids. These results convincingly demonstrate that FLDK-P70 may be useful for the prevention and treatment of ischemia/reperfusion injury and other related neurodegenerative diseases.
Bei
Weijian
W
The Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou, PR China.
Zang
Linquan
L
Guo
Jiao
J
Peng
Wenlie
W
Xu
Anlong
A
Good
David A
DA
Hu
Yinming
Y
Wu
Wei
W
Hu
Dehui
D
Zhu
Xinghong
X
Wei
Ming
M
Li
Chuyuan
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000633:toxicity; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
C547104:FLDK-P70; D005419:Flavonoids; D018696:Neuroprotective Agents; D018698:Glutamic Acid