The Garlic Compound Z-Ajoene, S-Thiolates Cox2 And Stat3 And Dampens The Inflammatory Response In Raw264.7 Macrophages
MOLECULAR NUTRITION & FOOD RESEARCH(2021)
摘要
Scope Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent to control inflammation-associated pathologies. To investigate the underlying mechanisms, an in vitro inflammatory model is established using RAW264.7 murine macrophages exposed to low-doses of lipopolysaccharide (LPS) in the presence of garlic compounds allicin and Z-ajoene (ZA), mimicking regular garlic consumption.Methods and Results Both allicin and Z-ajoene dampen both transcript and protein expression of the pro-inflammatory cytokines IL1 beta, IL6, and IL12 beta, and upregulate the expression of the anti-inflammatory cytokine IL10. Protein arrays of selected secreted inflammatory mediators confirm that Z-ajoene has a pronounced down-regulatory effect on LPS-induced inflammatory cytokines and chemokines. Many of these proteins are known targets of the transcription factor signal transducer and activator of transcription 3 (STAT3); and indeed, Z-ajoene or its analogue dansyl-ajoene is found to decrease phosphorylation and nuclear translocation of STAT3, and to covalently modify the protein by S-thiolation at Cys108, Cys367, and Cys687. Z-Ajoene dose-dependently and non-competitively inhibit the activity of cyclooxygenase 2 (COX2), possibly attributed to S-thiolation at Cys9 and Cys299.Conclusion The characterization of Z-ajoene's activity of targeting and covalently modifying STAT3 and COX2, both important regulators of inflammation, may contribute to the health benefits of regular dietary garlic consumption.
更多查看译文
关键词
ajoene, anti‐, inflammatory, COX2, garlic, NSAID, nutraceutical, STAT3
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要