Anti-neuroinflammatory Effects of 12-Dehydrogingerdione in LPS-Activated Microglia through Inhibiting Akt/IKK/NF-κB Pathway and Activating Nrf-2/HO-1 Pathway.
10.4062/biomolther.2018.104
- Author:
Dong ZHAO
1
;
Ming Yao GU
;
Jiu Liang XU
;
Li Jun ZHANG
;
Shi Yong RYU
;
Hyun Ok YANG
Author Information
1. Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 25457, Republic of Korea. hoyang@kist.re.kr
- Publication Type:Original Article
- Keywords:
Ginger;
12-Dehydrogingerdione;
Neuro-inflammation;
Microglial cells;
Signaling pathway
- MeSH:
Dietary Supplements;
Ginger;
Heme Oxygenase (Decyclizing);
Interleukins;
Microglia*;
Nitric Oxide;
Nitric Oxide Synthase;
Prostaglandin-Endoperoxide Synthases;
Spices;
Tumor Necrosis Factor-alpha;
Zinc
- From:Biomolecules & Therapeutics
2019;27(1):92-100
- CountryRepublic of Korea
- Language:English
-
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)-α, prostaglandin (PG) E₂, 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-κB 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-α by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting Akt/IKK/IκB/NF-κB pathway and promoting Nrf-2/HO-1 pathway.