Effects of S-allylcysteine on Nitric Oxide Production and Antioxidant Enzyme Activities in Hyperlipidemic Model Rats / 医药导报

Objective To investigate the effects of S-allylcysteine ( SAC ) , on nitric oxide ( NO ) production and antioxidant enzyme activities in hyperlipidemic rats. Methods Male Wistar rats were randomly divided into seven groups. Five groups including normal control group ( normal diet) , model control group ( high-fat diet, HFD) and SAC low,medium,high treated group (high-fat diet +25,50,100 mg·kg-1 SAC) were sacrificed after 4 weeks dosing,while the other two groups including L-arginine group (normal diet+ 20 mg·kg-1 L-arginine) and SAC+L-arginine group (50 mg·kg-1 SAC+20 mg·kg-1 L-arginine) were sacrificed at 4 h after dosing. The serum, livers and kidneys were collected. The levels of NO, the activities of nitric oxide synthase ( NOS ) , antioxidant enzymes in vivo and L-arginine contents in serum were determined. Results Comparing with model control group, the activities of total NOS in serum and liver were significantly reduced in SAC-treated groups (P<0. 05). The level of L-arginine in SAC-treated groups was (8. 25 ± 1. 15), (7. 76 ± 1. 24) and (7. 22 ± 1. 64)μg·mL-1 , respectively. Compared with model control group, the level of L-arginine were significantly reduced in SAC-treated groups (P<0. 05). Comparing with L-arginine group, the activities of total NOS (T-NOS) and iNOS were reduced in SAC+L-arginine group. SAC treatment (100 mg·kg-1) significantly increased the activities of superoxide dismutase (SOD) (P<0. 01) and the level of glutathione (GSH) (P<0.01), and decreased the level of malondialdehyde (MDA) in serum and liver of hyperlipidemic rats. Conclusion These data suggest that SAC inhibits the NO production by reducing iNOS activity, arginine concentration and exhibited antioxidant activity, which may play a pharmacologically important role in protection from oxidative injury and pathogenesis of atherosclerosis.

The Effect of Garlic Derivatives (S-Allylmercaptocysteine, Diallyl Disulfide, and S-Allylcysteine) on Gentamicin Induced Ototoxicity: An Experimental Study

OBJECTIVES: Gentamicin is a potent aminoglycoside antibiotic. Ototoxicity and nephrotoxicity are the main side effects which restrict the use of gentamicin. Garlic with its intrinsic antioxidant activity may prove beneficial in prevention from ototoxicity. S-allylmercaptocysteine (SAMC), diallyl disulfide (DD), and S-allylcysteine (SAC) are three active compounds found in garlic. In this study, we investigated the effect of SAMC, DD, and SAC on the ototoxicity induced by gentamicin in rats, by using brainstem evoked response audiometry (BERA). METHODS: Thirty male Wistar rats with intact Preyer’s reflex initially weighing 220–260 g were randomly assigned to either the gentamicin injection with SAMC treatment group (Genta-w SAMC), DD treatment group (Genta-w DD), SAC treatment group (Genta-w SAC), gentamicin injection without any active compounds (AC) treatment groups (Genta-w/o AC), or control group (n=6 rats each group). Gentamicin was given 120-mg/kg body weight, intraperitoneally once daily for 25 days to subjects in all groups except the control group. SAMC 100-mg/kg, and DD 50-mg/kg body weight were given intragastrically, and SAC 250-mg/kg body weight was given intraperitoneally once daily to subjects in Genta-w SAMC, and Genta-w DD, and Genta-w SAC groups, respectively during the study. After 25 days hearing thresholds were evaluated by using BERA test. RESULTS: The mean amplitude of auditory thresholds (sensation level [SL]) measured by using BERA for the Genta-w SAMC, Genta-w DD, Genta-w SAC, Genta-w/o AC, and control groups were 22±8, 25±5, 30±9, 54±11, and 10±7 dB SL, respectively (mean±SD). The differences between every active compound group (Genta-w SAMC, Genta-w DD, and Genta-w SAC) and Genta-w/o AC were statistically significant (P<0.016). CONCLUSION: SAMC, DD, and SAC are derivative of garlic seems to attenuate aminoglycoside-induced hearing loss. The effect of SAMC and DD seems to be more prominent than that of SAC.

Aged garlic extract and S-allylcysteine prevent apoptotic cell death in a chemical hypoxia model

BACKGROUND: Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells. RESULTS: We found that CoCl2 induced the stabilization of HIF-1α and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1α stabilization, activity not previously reported for AGE and SAC. CONCLUSIONS: Obtained results show that AGE and SAC decreased apoptotic CoCl2-induced cell death. This protection occurs by affecting the activity of HIF-1α and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

PURPOSE: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. MATERIALS AND METHODS: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). RESULTS: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. CONCLUSION: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.