Curcumin Protects against 1-Methyl-4-phenylpyridinium Ion- and Lipopolysaccharide-Induced Cytotoxicities in the Mouse Mesencephalic Astrocyte via Inhibiting the Cytochrome P450 2E1

Hai-Yan Gui,Gang Hu,Zhao Mao,Wei Shang,Yan Peng,Jin-Hua Hu,Jing Xiong,Jian Yang,Rui-Ni Chen,Rui Ning,Wei Liu

doi:10.1155/2013/523484

Abstract

Curcumin is extracted from the rhizomes of the ginger family plant Curcuma longa L., which has a good protection for liver, kidney, and immune system. However, there is little information about its contribution in protection of astrocytes recently. The present study was undertaken to elucidate the protective effect of curcumin, an herbal antioxidant, on 1-methyl-4-phenylpyridinium ion- (MPP+-) and lipopolysaccharide- (LPS-) induced cytotoxicities, as well as the underlying mechanisms by using primary mouse mesencephalic astrocytes. The results showed that curcumin protected the mesencephalic astrocytes from MPP+- and LPS-induced toxicities along with reducing reactive oxygen species (P < 0.05) and maleic dialdehyde (P < 0.05) sufficiently. Moreover, curcumin significantly inhibited the cytochrome P450 2E1 (CYP2E1) expression (P < 0.01 at mRNA level, P < 0.05 at protein level) and its activity (P < 0.05) sufficiently induced by MPP+ and LPS in the mouse mesencephalic astrocytes. And curcumin as well as diallyl sulphide, a CYP2E1 positive inhibitor, ameliorated MPP+- and LPS-induced mouse mesencephalic astrocytes damage. Accordingly, curcumin protects against MPP+- and LPS-induced cytotoxicities in the mouse mesencephalic astrocyte via inhibiting the CYP2E1 expression and activity.

Highlights

Curcumin (1,7-bis[4-hydroxy 3-methoxy phenyl]-1,6-heptadiene-3,5-dione, Curcumin reactive oxygen species (ROS) (Cur)) is extracted from the rhizomes of the ginger family plant Curcuma longa (Curcuma longa L.)
The body of mesencephalic astrocytes which were treated with high concentrations (30 μM, 50 μM) of Curcumin ROS (Cur) became more asperous with shrunken morphologies, and processes of mesencephalic astrocytes were reduced in size and decreased in number (Figure 1(c))
In order to test this probability, we further investigated the effects of Cur on the cytochrome P450 2E1 (CYP2E1) expression and activity in the mesencephalic astrocytes induced by MPP+, LPS and ethyl alcohol (EtOH)

Summary

Introduction

Curcumin (1,7-bis[4-hydroxy 3-methoxy phenyl]-1,6-heptadiene-3,5-dione, Cur) is extracted from the rhizomes of the ginger family plant Curcuma longa (Curcuma longa L.). Astrocytes are allowed by some specific enzyme systems to metabolize ammonia, glutamate, free radicals, xenobiotics, and metals. They protect the neurons from the endogenous and exogenous toxicities. CYP2E1 is constitutively expressed in hippocampal pyramid neurons, astrocytes, and endothelial cells [17], and CYP2E1 has been found to be inducible and catalytically active in the central nervous system [18,19,20]. It has been suggested that 1-methyl4-phenylpyridinium ion (MPP+, the ion form of 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine, MPTP) and lipopolysaccharide (LPS) increased the expression of CYP2E1 and induced oxidative stress in astrocytes [18, 19]. The increasing evidence shows that CYP2E1 is involved in the MPTPinduced mouse model of PD [21, 22]

Methods

Results

Discussion

Conclusion