The neuroprotection effects of a cognitiive-enhancing herb Alpinae Oxyphyllae and its component chrysin on glutamate-induced neurotoxicity

Abstract

Neuroprotection is a strategy to protect neurons in the central nervous system (CNS) following acute injury or chronic neurodegenerative disease, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Natural herbs have long been used in Asian societies for treating neurodegenerative disorders. In an effort to find effective neuroprotective compounds from herbal medicine, glutamate-induced neurotoxicity on cultured rat cortical neurons was employed as an in vitro model in our screening program. Twelve 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 the herbs being tested, the fruit of Alpinae Oxyphyllae, which is traditionally regarded as a cognitive-enhancing herb, was found to have the most potent activity in attenuating the glutamate-induced cell death. Pretreatment of A. Oxyphyllae fruit extract significantly reduced lactate dehydrogenase (LDH) release and the glutamate-triggered activation of caspase-3 in cultured cortical neurons. In addition, A. Oxyphyllae was able to mitigate the neurotoxicity when co-cultured or post-treated with glutamate. Also, A. Oxyphyllae could effectively reduce the H2O2 neurotoxicity. Further isolation and purification were performed of the alcoholic extract of A. Oxyphyllae, and one active compound namely chrysin was obtained. Pretreatment of this compound in cortical neurons could significantly reduce LDH release and the glutamate-induced activation of caspase-3. We further showed that chrysin could significantly reduce the H2O2 neurotoxicity and oxidative stress induced by glutamate. Western-blot analysis demonstrated that chrysin markedly attenuated glutamate-triggered phosphorylation of JNK. Taken together, our results shows the neuroprotective effects of A. Oxyphyllae and one of its compound chrysin, which may have potential to expand its usages as neuroprotective agent and potentially use in both symptom-relieving as well as disease-modifying drug.