Neuroprotective effects of a standardized flavonoid extract from Diospyros kaki leaves.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

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.

AIM OF THE STUDY:

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.

MATERIALS AND METHODS AND 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.

• Authors: Weijian Bei, Linquan Zang, Jiao Guo, Wenlie Peng, Anlong Xu, David A Good, Yinming Hu, Wei Wu, Dehui Hu, Xinghong Zhu, Ming Wei, Chuyuan Li
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 126 Issue 1 Pg. 134-42 (Oct 29 2009) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 19665536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FLDK-P70
• Flavonoids
• Neuroprotective Agents
• Glutamic Acid

Topics

• Animals
• Apoptosis (drug effects)
• CA1 Region, Hippocampal (drug effects, pathology)
• Cell Culture Techniques
• Cell Death (drug effects)
• Cerebral Cortex (drug effects, pathology)
• Disease Models, Animal
• Flavonoids (chemistry, therapeutic use)
• Glutamic Acid (toxicity)
• Ischemic Attack, Transient (drug therapy)
• Male
• Neurons (drug effects, pathology)
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy)