Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/MAPK and NFκB Translocation

  • Xian, Zhou (NICM Health Research Institute, Western Sydney University) ;
  • Ahmad, Al-Khazaleh (NICM Health Research Institute, Western Sydney University) ;
  • Sualiha, Afzal (School of Medicine, Western Sydney University) ;
  • Ming-Hui (Tim), Kao (School of Medicine, Western Sydney University) ;
  • Gerald, Munch (School of Medicine, Western Sydney University) ;
  • Hans, Wohlmuth (NICM Health Research Institute, Western Sydney University) ;
  • David, Leach (Integria Healthcare) ;
  • Mitchell, Low (NICM Health Research Institute, Western Sydney University) ;
  • Chun Guang, Li (NICM Health Research Institute, Western Sydney University)
  • Received : 2022.03.15
  • Accepted : 2022.08.18
  • Published : 2023.01.01
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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-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-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.

Keywords

Acknowledgement

This study was supported by the Linkage Project from the Australian Research Council (ARC) grant (LP160101594). As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals and industry. Sponsors and donors also provide untied funding for work to advance the vision and mission of the Institute.

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