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Abstract Title:

The Garlic Compound Z-Ajoene, S-Thiolates COX2 and STAT3 and Dampens the Inflammatory Response in RAW264.7 Macrophages.

Abstract Source:

Mol Nutr Food Res. 2021 02 ;65(3):e2000854. Epub 2020 Dec 18. PMID: 33274836

Abstract Author(s):

Jessica K Hitchcock, Nonkululeko Mkwanazi, Christopher Barnett, Lisa M Graham, Arieh A Katz, Roger Hunter, Georgia Schäfer, Catherine H Kaschula

Article Affiliation:

Jessica K Hitchcock

Abstract:

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 IL1β, IL6, and IL12β, 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.

Study Type : In Vitro Study

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