Cudratricusxanthone A Protects Mouse Hippocampal Cells against Glutamate-Induced Neurotoxicity via the Induction of Heme Oxygenase-1

Abstract

Cudratricusxantone A (CTXA), isolated from the roots of Cudrania tricuspidata Bureau (Moraceae), has potent hepatoprotective, antiproliferative, and monoamine oxidase inhibitory effects. In this study, we examined whether CTXA could protect HT22-immortalized hippocampal cells against glutamate-induced oxidative stress through the induction of heme oxygenase (HO)-1 expression. CTXA induced the expression of HO-1 and increased HO activity dose- and time-dependently. CTXA also suppressed glutamate-induced ROS generation in HT22 cells. Interestingly, treatment of neuronal cells with CTXA enhanced cellular resistance to glutamate oxidative stress. The protective effect of CTXA was abrogated by tin protoporphyrin IX, an HO inhibitor. In addition, treatment with the HO-1 inducer, cobalt protoporphyrin IX, and bilirubin, one of the enzymatic products of HO-1, produced comparable protection. These results demonstrate that CTXA protects neuronal cells from glutamate-induced oxidative stress via the induction of HO-1.

Abbreviations

CoPP:cobalt protoporphyrin IX

CTXA:cudratricusxanthone A

CDFDA:2′,7′-dichlorofluorescein diacetate

HO:heme oxygenase

SnPP:tin protoporphyrin IX

Key words

cudratricusxanthone A - Cudrania tricuspidata Bureau - Moraceae - heme oxygenase-1 - HT22, glutamate - cytoprotection

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1 These authors contributed equally to this work.