Biomol Ther.  2019 Jan;27(1):92-100. 10.4062/biomolther.2018.104.

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 D
• Gu MY
• Xu JL
• Zhang LJ
• Ryu SY
• Yang HO

• KMID: 2432072
• DOI: http://doi.org/10.4062/biomolther.2018.104

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.

Keyword

Ginger; 12-Dehydrogingerdione; Neuro-inflammation; Microglial cells; Signaling pathway

MeSH Terms

Dietary Supplements
Ginger
Heme Oxygenase (Decyclizing)
Interleukins
Microglia*
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Spices
Tumor Necrosis Factor-alpha
Zinc
Heme Oxygenase (Decyclizing)
Interleukins
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Tumor Necrosis Factor-alpha
Zinc