s-allylcysteine and Neurodegenerative-Diseases

The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). DATS and diallyl disulfide at 200 and 400 μM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases.

Topics: Allium; Allyl Compounds; Animals; Cell Line; Chemokine CCL2; Cysteine; Disulfides; Garlic; Inflammation; Interleukin-1beta; Lipopolysaccharides; Mice; Microglia; Neurodegenerative Diseases; NF-kappa B; Nitric Oxide; Plant Extracts; Sulfides; Sulfur Compounds; Tumor Necrosis Factor-alpha

The functional preservation of nerve endings since the early stages of toxicity in a given damaging insult-either acute or chronic-by means of antioxidant and neuroprotective agents is a primary need to design therapeutic strategies for neurodegenerative disorders, with particular emphasis on those diseases with excitotoxic and depleted energy metabolism components. S-allylcysteine (SAC), a well-known antioxidant agent, was tested as a post-treatment in different in vitro and in vivo neurotoxic models. Quinolinic acid (QUIN) was used as a typical excitotoxic/pro-oxidant inducer, 3-nitropropionic acid (3-NP) was employed as a mitochondrial function inhibitor, and their combination (QUIN + 3-NP) was also evaluated in in vitro studies. For in vitro purposes, increasing concentrations of SAC (10-100 microM) were added to isolated brain synaptosomes at different times (1, 3 and 6 h) after the incubation with toxins (100 microM QUIN, 1 mM 3-NP or the combination of QUIN (21 microM) + 3-NP (166 microM). Thirty minutes later, lipid peroxidation (LP) and mitochondrial dysfunction (MD) were evaluated. For in vivo studies, SAC (100 mg/kg, i.p.) was given to QUIN- or 3-NP-striatally lesioned rats for 7 consecutive days (starting 120 min post-lesion). LP and MD were evaluated 7 days post-lesion in isolated striatal synaptosomes. Circling behavior was also assessed. Our results describe a differential pattern of protection achieved by SAC, mostly expressed in the 3-NP toxic model, in which nerve ending protection was found within the first hours (1 and 3) after the toxic insult started, supporting the concept that the ongoing oxidative damage and energy depletion can be treated during the first stages of neurotoxic events.

Topics: Animals; Antioxidants; Brain; Corpus Striatum; Cysteine; Disease Models, Animal; Dyskinesia, Drug-Induced; Lipid Peroxidation; Male; Mitochondria; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Nitro Compounds; Oxidative Stress; Propionates; Quinolinic Acid; Rats; Rats, Wistar; Synaptosomes; Time Factors