Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Molecular nutrition & food research, 2021-02, Vol.65 (3), p.e2000854-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Wiley Online Library

Beschreibungen/Notizen

• 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. The garlic compound Z‐ajoene is found in cooked or aged garlic preparations. It is a natural non‐steroidal anti‐inflammatory drug and potent thiophile, able to S‐thiolate cysteine sulfhydryl groups in two inflammatory proteins, namely signal transducer and activator of transcription 3 (STAT3) and cyclooxygenase 2 (COX 2), leading to downstream anti‐inflammatory effects.