Significance of a Cognition-Enhancing Chinese Herb Frustus Alpiniae oxyphyllae as a Source for Potential Neuroprotective Agents.

摘要

Neuroprotection is the mechanisms and strategies used to protect against neuronal injury or degeneration in the central nervous system (CNS) following acute disorder or a result of chronic neurodegenerative disease, such as Glaucoma, Alzheimer's disease (AD) and Parkinson's disease (PD).;Further isolation and purification were performed on the alcoholic extract of FAO, and one active compound, namely chrysin, was obtained. Pretreatment of this compound in cortical neurons could significantly reduced LDH release and the glutamate-triggered activation of caspase-3. In addition, chrysin could dramatically reduce the H2O2-induced neurotoxicity and oxidative stress induced by glutamate.;Glaucoma represents a group of neurodegerative diseases characterized by structural damage to the optic nerve and slow, progressive death of retinal ganglion cells (RGCs). To test the anti-glaucoma action of chrysin, we used the chronic ocular hypertension glaucoma model as an in vivo animal model. Our results showed that a single intravitreous injection of chrysin was effective in rescuing RGCs in the chronic ocular hypertension glaucoma rats and the effects could last for 4 weeks.;Taken together, the present PhD project has identified FAO and one of its compounds chrysin to have potent neuroprotective effects. The discovery may expand the clinical usages of FAO as a neuroprotective agent and paves the way for further development of chrysin into a pharmaceutical agent for neuogenerative diseases.;Natural herbs have long been used in Asian societies for treating neurodegenerative disorders. In an effort to find effective neuroprotective compounds from Chinese medicine, glutamate-induced neurotoxicity on cultured rat cortical neurons was employed as an in vitro model in our screening programme. Twelve Chinese herbs were selected for this project based on their ethnomedical use in the treatment of neurodegenerative disorders. Alcoholic extracts of these Chinese medicines were investigated for their neuroprotective action. Among all the herbs tested, Fructus Alpiniae oxyphyllae (FAO), or Yi Zhi Ren in Chinese, which is traditionally regarded as a cognition-enhancing herbal drug, was found to have the most potent activity in attenuating the glutamate-induced cell death. Pretreatment of FAO extract significantly reduced lactate dehydrogenase (LDH) release and the glutamate-triggered activation of caspase-3 in cultured cortical neurons. In addition, FAO was able to mitigate the neurotoxicity when co-cultured or post-treated with glutamate. Moreover, FAO could effectively rescue the H2O2-caused neurotoxicity. These experimental findings render FAO a promising neuroprotective crude drug.