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S ‐allyl cysteine alleviates nonsteroidal anti‐inflammatory drug‐induced gastric mucosal damages by increasing cyclooxygenase‐2 inhibition, heme oxygenase‐1 induction, and histone deacetylation inhibition
Author(s) -
Park JongMin,
Han YoungMin,
Kangwan Napapan,
Lee SooYeon,
Jung MiKyoung,
Kim EunHee,
Hahm KiBaik
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12730
Subject(s) - medicine , cyclooxygenase , pharmacology , ibuprofen , inflammation , myeloperoxidase , heme oxygenase , tumor necrosis factor alpha , immunology , biochemistry , enzyme , heme , chemistry
Background and Aim Nonsteroidal anti‐inflammatory drugs ( NSAID s), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, are associated with gastric mucosal damages including ulcer directly or indirectly. This study was aimed to document the preventive effects of an organosulfur constituent of garlic, S ‐allyl cysteine ( SAC ), against NSAID s‐induced gastric damages, as well the elucidation of its pharmacological actions, such as anti‐inflammatory, anti‐oxidative, and cytoprotective actions. Methods Different doses of SAC were administrated intragastrically before the indomethacin administration. After killing, in addition to gross and pathological evaluations of ulcer, the expressions of inflammatory mediators, including cyclooxygenase‐2, prostaglandin E 2 , IL ‐1β, tumor necrosis factor‐α, IL ‐6, and anti‐oxidant capacity, were analyzed by W estern blot analysis or ELISA , respectively. Transferase deoxytidyl uridine end labeling assay, periodic acid and S chiff staining, F 4/80 staining, and CD 31 staining were compared among doses of SAC . Detailed documentation of in vitro biological actions of SAC , including NF ‐κ B , histone deacetylator inhibition, phase 2 enzyme, and MAPK s, was performed. Results SAC was very effective in preventing indomethacin‐induced gastric damages in a low dose through significant decreases in macrophage infiltration as well as restorative action. Indomethacin‐induced expressions of inflammatory mediators were all significantly attenuated with SAC in accordance with histone deacetylator inhibition. In addition, SAC significantly increased the total anti‐oxidant concentration and mucus secretion, and allows for a significant induction of HO ‐1. However, these preventive effects of SAC were dependent on dosage of SAC ; higher dose above 10 μM paradoxically aggravated NSAID ‐induced inflammation. Conclusion Synthetic SAC can be promising therapeutics agent to provide potent anti‐inflammatory, anti‐oxidative, and mucosa protective effects against NSAID ‐induced damages.