Biomolecules & Therapeutics  
Anti-neuroinflammatory Effects of 12-Dehydrogingerdione in LPS-Activated Microglia through Inhibiting Akt/IKK/NF-κB Pathway and Activating Nrf-2/HO-1 Pathway
Dong Zhao1,2, Ming-Yao Gu1, Jiu Liang Xu1, Li Jun Zhang1,2, Shi Yong Ryu3 and Hyun Ok Yang1,2,*
1Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 25457,
2Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792,
3Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon 34113, Republic of Korea
E-mail: hoyang@kist.re.kr
Tel: +82-33 650 3501, Fax: +82-33 650 3529
Received: June 4, 2018; Revised: August 24, 2018; Accepted: August 31, 2018; Published online: October 26, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Ginger, one of worldwide consumed dietary spice, in fact, it is not only famous as food supplements, and 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-induce dinterleukin (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.
Keywords: Ginger, 12-Dehydrogingerdione, Neuro-inflammation, Microglial cells, Signaling pathway


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