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Multi-target effects of 3-n-Butylphalide, a component of Apium graveolens L., in treatment of neurodegenerative diseases

[Speaker] Xiaoliang Wang:1
[Co-author] Ying Peng:1, Ling Wang:1, Jiang Li:1, Shaofeng Xu:1, Nan Feng:1, Weiping Wang:1
1:Department of pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, China

L-3-n-Butylphalide (l-NBP) was isolated from seeds of Apium graveolens L. by the Institute of Materia Medica. CAMS in the 1980s. It was showed to be effective in anti-epilepsy. Soon it was synthesized as a racemic form, dl-3-n-butylphalide (dl-NBP) and demonstrated that dl-NBP had the similar pharmacological effects compared to l-NBP. In 1990s dl-NBP was found to be potent in protection of brain injury from cerebral ischemia in animal models. It was approved by SFDA for clinical trial and was approved as a new drug for acute ischemic stroke in 2005. Today, dl-NBP is a frequently used drug for treatment of ischemic stroke in China.
The pharmacological study showed that l-NBP/dl-NBP inhibited ADP induced platelet aggregation through P2Y12 receptor signaling pathways, reduced thrombus formation, increased regional cerebral blood flow, protected the function of mitochondria and inhibited the cell apoptosis during cerebral ischemia. It was also found that l-NBP could significantly enhance hippocampal neurogenesis and neuroplasticity after cerebral ischemia in rats. The activation effects of CREB and Akt and inhibitory effect of STAT3 signaling pathways might be involved in.
Furthermore, we found recently that dl-NBP/dl-NBP had very interesting effects except its anti-stroke. NBP may reduce the levels of beta-amyloid and tau phosphorylation in cell lines, brains of aged rats and transgenic mice model of Alzheimer's disease. The targets of NBP for above effects might be PKC related signal transduction system and the GSK3beta as well as CDK5, respectively. NBP may improve the cognitive ability was also seen in AD and VAD animal models. Therefore, NBP appears to be promising as a multi-target drug for the prevention and/or treatment of Alzheimer's disease and vascular dementia. It has been in phase 2, 3 clinic trial for dementia.
Conclusion:Our study showed that the Chinese herb medicine is a good resource for discovery and development of novel drugs to treat neurodegenerative diseases.

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