Abstract
Many degenerative or pathological processes, such as aging, cancer and coronary heart disease, are related to reactive oxygen species (ROS) and radical-mediated reactions. We examined the effectiveness of aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, for protection of cells from ROS produced by 6-hydroxy-dopamine (6-OHDA) using human neuroblastoma SH-SY5Y cells. Concomitant treatment of cells with AGE (2 and 4 mg/ml) showed the dose-dependent protective effect on the cell death induced by 6-OHDA. In addition, the AGE treatment significantly suppressed the increase of ROS generation by 6-OHDA. Furthermore, the protective effect of AGE was accompanied by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the increase of mRNAs of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. These two enzymes are important in the cellular antioxidant system. These results indicated that AGE protected cells from ROS damage by not only capturing ROS directly but also activating the cellular antioxidant system by stimulating antioxidant gene expression via the Nrf2-ARE pathway. The present study suggested that AGE may be useful for prevention and treatment of cell damage caused by ROS.
Highlights
Garlic (Allium sativum L.) has been used for the prevention and treatment of a variety of diseases including heart disease and cancer [1]
6-OHDA, MPP+ and ACNU, that induce cytotoxicity in nerve cells were chosen and the protective effect of aged garlic extract (AGE) (2 and 4 mg/ml) on cell death induced by these compounds was examined. 6-OHDA is a potent neurotoxin and induces cell death associated with reactive oxygen species (ROS) generation [20], whereas MPP+ is an inducer of Parkinsonism and inhibitor of mitochondrial respiration chain [34] and ACNU is an alkylating anticancer drug used for the therapy of brain cancer [35]
These results indicated that among three test compounds examined, the protective effect of AGE on cell death was only observed in the case of 6-OHDA that produced ROS
Summary
Garlic (Allium sativum L.) has been used for the prevention and treatment of a variety of diseases including heart disease and cancer [1]. AGE has been shown to possess superior antioxidant properties compared to the raw garlic, which may be important for its pharmacological effects [11]. Aged Garlic Extract Reduces ROS Production and Cell Death Induced by 6-Hydroxydopamine through. 6-Hydroxydopamine (6-OHDA) is one of potent neurotoxins and induces cell death associated with ROS generation [20]. When cells undergo certain adverse conditions such as oxidative stress, Nrf is liberated from Keap, and allowed to translocate into the nucleus and bind to ARE [28,29]. We examined the protective effect of AGE on the cell death induced by 6-OHDA and its ability to activate antioxidant systems in cultured SHSY5Y cells. Our results indicated that AGE effectively inhibited the cell death induced by ROS through capturing ROS directly and inducting antioxidant gene expression via the Nrf2-ARE pathway. AGE may be useful for the prevention and treatment of diseases associated with ROS
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