Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Anti-neuroinflammatory Effects of 12-Dehydrogingerdione in LPS-Activated Microglia through Inhibiting Akt/IKK/NF-κB Pathway and Activating Nrf-2/HO-1 Pathway

  • Zhao, Dong (Natural Products Research Center, Korea Institute of Science and Technology) ;
  • Gu, Ming-Yao (Natural Products Research Center, Korea Institute of Science and Technology) ;
  • Xu, Jiu Liang (Natural Products Research Center, Korea Institute of Science and Technology) ;
  • Zhang, Li Jun (Natural Products Research Center, Korea Institute of Science and Technology) ;
  • Ryu, Shi Yong (Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology) ;
  • Yang, Hyun Ok (Natural Products Research Center, Korea Institute of Science and Technology)
  • Received : 2018.06.04
  • Accepted : 2018.08.31
  • Published : 2019.01.01
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Abstract

Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.

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References

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