姜黄素衍生物 2,6-双（2-氟苯亚甲基）环己酮（MS65）通过抑制组胺诱导的人角质形成细胞（HaCaT）中的 NF-κB 和 MAPK 通路抑制白细胞介素-6 的产生。
Curcumin derivative, 2,6-bis(2-fluorobenzylidene)cyclohexanone (MS65) inhibits interleukin-6 production through suppression of NF-κB and MAPK pathways in histamine-induced human keratinocytes cell (HaCaT).
机构信息
Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
出版信息
BMC Complement Altern Med. 2018 Jul 16;18(1):217. doi: 10.1186/s12906-018-2223-8.
BACKGROUND
Histamine is a well-known mediator involved in skin allergic responses through up-regulation of pro-inflammatory cytokines. Antihistamines remain the mainstay of allergy treatment, but they were found limited in efficacy and associated with several common side effects. Therefore, alternative therapeutic preferences are derived from natural products in an effort to provide safe yet reliable anti-inflammatory agents. Curcumin and their derivatives are among compounds of interest in natural product research due to numerous pharmacological benefits including anti-inflammatory activities. Here, we investigate the effects of chemically synthesized curcumin derivative, 2,6-bis(2-fluorobenzylidene)cyclohexanone (MS65), in reducing cytokine production in histamine-induced HaCaT cells.
METHODS
Interleukin (IL)-6 cytokine production in histamine-induced HaCaT cells were measured using enzyme-linked immunosorbent assay (ELISA) and cytotoxicity effects were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-qPCR) was carried out to determine the inhibitory effects of MS65 on nuclear factor-kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways.
RESULTS
Histamine enhanced IL-6 production in HaCaT cells, with the highest production of IL-6 at 97.41 ± 2.33 pg/mL after 24 h of exposure. MS65 demonstrated a promising anti-inflammatory activity by inhibiting IL-6 production with half maximal inhibitory concentration (IC) value of 4.91 ± 2.50 μM and median lethal concentration (LC) value of 28.82 ± 7.56 μM. In gene expression level, we found that MS65 inhibits NF-κB and MAPK pathways through suppression of IKK/IκB/NFκB and c-Raf/MEK/ERK inflammatory cascades.
CONCLUSION
Taken together, our results suggest that MS65 could be used as a lead compound on developing new medicinal agent for the treatment of allergic skin diseases.
背景
组胺是一种众所周知的介质，通过上调促炎细胞因子参与皮肤过敏反应。抗组胺药仍然是过敏治疗的主要药物，但它们的疗效有限，且存在几种常见的副作用。因此，人们从天然产物中寻找替代治疗方法，以提供安全可靠的抗炎药物。姜黄素及其衍生物是天然产物研究中感兴趣的化合物之一，因为它们具有许多药理学益处，包括抗炎活性。在这里，我们研究了化学合成的姜黄素衍生物 2,6-双（2-氟苯亚甲基）环己酮（MS65）在减少组胺诱导的 HaCaT 细胞中细胞因子产生的作用。
方法
用酶联免疫吸附测定（ELISA）法测定组胺诱导的 HaCaT 细胞中白细胞介素（IL）-6 细胞因子的产生，用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法测定细胞毒性作用。实时聚合酶链反应（RT-qPCR）用于确定 MS65 对核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）途径的抑制作用。
结果
组胺增强 HaCaT 细胞中 IL-6 的产生，暴露 24 小时后 IL-6 的最高产量为 97.41±2.33pg/mL。MS65 通过抑制 IL-6 的产生显示出有希望的抗炎活性，其半最大抑制浓度（IC）值为 4.91±2.50μM，半数致死浓度（LC）值为 28.82±7.56μM。在基因表达水平上，我们发现 MS65 通过抑制 IKK/IκB/NFκB 和 c-Raf/MEK/ERK 炎症级联反应抑制 NF-κB 和 MAPK 途径。
结论
综上所述，我们的结果表明，MS65 可作为开发治疗过敏性皮肤病新药物的先导化合物。
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