Among these preparations, S-allyl cysteine (SAC), one of the major organic garlic compounds that had been known to possess a powerful anti-oxidant property, can be candidate for potential formula compared with other organosulfur compounds, including diallyl bisulfide, diallyl trisulfide (DAT3S), or diallyl-tetrasulfide (DAT4S).[9, 10] Studies in mouse and rodent models have shown that SAC can be rapidly absorbed in the GI tract and has very low acute/subacute toxicity (LD50 value > 54.7 mM/kg oral; > 20 mM/kg intraperitoneal), which is 30-fold less toxic than other typical garlic compounds, such as allicin Selleck Ruxolitinib and diallyl disulfide.[11, 12] Moreover, SAC is two hydrophilic cysteine-containing compounds
naturally formed in CDK inhibitor garlic. It has been shown to exert anti-inflammatory and anti-oxidative effects in various models, but never been tried against GI inflammation. Recently, phytoceuticals or phytochemicals were proven to possess the ability to orchestrate gastric inflammation more globally through histone deacetylator (HDAC) inhibitory activity, as well as potentiate the host defensive phase enzyme induction like heme oxygenase-1 (HO-1) through nuclear factor erythroid-derived 2-related factor (Nrf2) transcriptional activation, a transcription factor that in humans
is encoded by the NFE2L2 gene, of which Nrf2 anti-oxidant response pathway is “the primary cellular defense” against the cytotoxic effects of oxidative stress, in our study provoked by indomethacin. The object of our study was either to document the preventive efficacy of selleckchem SAC against indomethacin-induced gastric damage or to identify the underlying molecular mechanisms on how SAC could impose protection. An animal model of indomethacin-induced gastric damage model was established, and tumor necrosis
factor-α (TNF-α)-stimulated cell models were used for current experiment. All chemical reagents were obtained from Sigma (St. Louis, MO, USA). Synthetic SAC was provided by Pharmaking Co., Ltd (Seongnam, Korea). Rebamipide was provided by Otsuka Pharmaceutical Co., Ltd (Tokushima, Japan). PD98095 and SB202190 were provided from Calbiochem (Billerica, MA, USA). Western blotting detection reagents were obtained from Amersham Biotechnology (Bucks, UK). Antibodies for COX-2, β-actin, inducible nitric oxide synthase (iNOS), α-tubulin, superoxide dismutase-1 (SOD-1), glutathione peroxidase-2 (GPX-2), glutathione-S-transferase-π (GST-π), Nrf2, γ-Glutamylcysteine Synthetase (γ-GCS), NAD(P)H:quinone oxidoreductase-1 (NQO-1), phospho-extracellular-signal-regulated kinase (pERK), and ERK were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Antibodies for calcium-dependent phospholipase A2 (cPLA2), phosphor-IκBα, IκBα, p65, p50, phospho-p38, and p38 were purchased from Cell Signaling Technology (Denver, MA, USA). Antibody for heme oxygenase 1 (HO-1) was from R&D Systems, Inc. (Minneapolis, MN, USA).