Anti-neuroinflammatory Effects of 12-Dehydrogingerdione in LPS-Activated Microglia through Inhibiting Akt/IKK/NF-κB Pathway and Activating Nrf-2/HO-1 Pathway
| Autor: | Ming-Yao Gu, Jiu Liang Xu, Hyun Ok Yang, Dong Zhao, Li Jun Zhang, Shi Yong Ryu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
12-Dehydrogingerdione Prostaglandin IκB kinase Pharmacology Ginger Biochemistry Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Protein kinase B Signaling pathway Interleukin NF-κB Heme oxygenase 030104 developmental biology chemistry Neuro-inflammation 030220 oncology & carcinogenesis Molecular Medicine Tumor necrosis factor alpha Original Article Microglial cells |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 2005-4483 1976-9148 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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