Diallyl sulfide as a potential dietary agent to reduce TNF‐α‐ and histamine‐induced proinflammatory responses in A7r5 cells

• Published in: Molecular nutrition & food research 2014-05, Vol.58 (5), p.1069-1078
• Main Authors: Ho, Cheng‐Ying, Weng, Chia‐Jui, Jhang, Jhih‐Jia, Cheng, Yu‐Ting, Huang, Shang‐Ming, Yen, Gow‐Chin
• Format: Article
• Language: English
• Subjects: Allyl Compounds - pharmacology; Animals; antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Cell Line; Diallyl sulfide; dissociation; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; garlic; Garlic - chemistry; Histamine; Histamine - adverse effects; Inflammation; Inflammation - drug therapy; Inflammation - prevention & control; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - metabolism; Myocytes, Smooth Muscle; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Nrf2; oxidative stress; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Phytochemicals - pharmacology; Rats; reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; smooth muscle; Sulfides - pharmacology; TNF Receptor-Associated Death Domain Protein - metabolism; TNF Receptor-Associated Factor 2 - metabolism; TNF-α; Transcription Factor AP-1 - metabolism; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201300617

SCOPE: Oxidative stress‐aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor‐alpha (TNF‐α)‐ or histamine‐induced inflammation in rat aortic smooth muscle A7r5 cells. METHODS AND RESULTS: A7r5 cells were coincubated with DAS before exposure to TNF‐α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF‐α‐induced A7r5 cells by attenuating the TNF‐α receptor complex through the dissociation of the TNF receptor‐associated death domain and TNF receptor‐associated factor 2. Moreover, DAS inhibited histamine‐induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor‐erythroid 2‐related factor 2‐related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin‐1β and TNF‐α through the inhibition of ROS‐induced PI3K/Akt and the downstream NF‐κB and activator protein‐1. CONCLUSION: Our results demonstrate that DAS is a potential phytochemical to inhibit TNF‐α‐ and histamine‐induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress‐induced inflammation of the airway.