6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/ MAPK and NFκB Translocation

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Abstract

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-ɣ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaol-curcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and inter-lukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

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Zhou, X., Al-Khazaleh, A., Afzal, S., Kao, M. H., Münch, G., Wohlmuth, H., … Li, C. G. (2023). 6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/ MAPK and NFκB Translocation. Biomolecules and Therapeutics, 31(1), 27–39. https://doi.org/10.4062/biomolther.2022.039

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