Zhao Dong, Gu Ming-Yao, Xu Jiu Liang, Zhang Li Jun, Ryu Shi Yong, Yang Hyun Ok
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 25457, Republic of Korea.
Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
Biomol Ther (Seoul). 2019 Jan 1;27(1):92-100. doi: 10.4062/biomolther.2018.104.
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.
生姜是全球消费的食用香料之一，不仅作为食品补充剂而闻名，还被认为作为草药具有多种显著的药理活性。在本研究中，一种生姜成分12-脱氢姜二酮（DHGD）被证明在抑制脂多糖（LPS）诱导的白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、前列腺素（PG）E₂、一氧化氮（NO）、诱导型NO合酶（iNOS）和环氧化酶（COX）-2方面具有与阳性对照6-姜酚相当的抗炎活性，且在培养的小胶质细胞中不干扰COX-1。随后的机制研究表明，12-DHGD可能通过抑制LPS激活的Akt/IKK/NF-κB途径来抑制神经炎症。此外，12-DHGD显著促进了NF-E2相关因子（Nrf）-2和血红素加氧酶（HO）-1的激活，并且我们通过使用HO-1抑制剂原卟啉锌（Znpp）证明了HO-1参与了NO和TNF-α等促炎介质的产生。这些结果表明，12-DHGD可能通过抑制Akt/IKK/IκB/NF-κB途径和促进Nrf-2/HO-1途径来预防神经炎症。
