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辣木异硫氰酸酯的α-环糊精复合物通过抑制Akt和p38来抑制脂多糖诱导的RAW 264.7巨噬细胞炎症。

The α-cyclodextrin complex of the Moringa isothiocyanate suppresses lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells through Akt and p38 inhibition.

作者信息

Giacoppo Sabrina, Rajan Thangavelu Soundara, Iori Renato, Rollin Patrick, Bramanti Placido, Mazzon Emanuela

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy.

Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria, Centro di ricerca Agricoltura e Ambiente (CREA-AA), Via di Corticella 133, 40128, Bologna, Italy.

出版信息

Inflamm Res. 2017 Jun;66(6):487-503. doi: 10.1007/s00011-017-1033-7. Epub 2017 Mar 13.

Abstract

In the last decades, a growing need to discover new compounds for the prevention and treatment of inflammatory diseases has led researchers to consider drugs derived from natural products as a valid option in the treatment of inflammation-associated disorders. The purpose of the present study was to investigate the anti-inflammatory effects of a new formulation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate as a complex with alpha-cyclodextrin (moringin + α-CD) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, a common model used for inflammation studies. In buffered/aqueous solution, the moringin + α-CD complex has enhanced the water solubility and stability of this isothiocyanate by forming a stable inclusion system. Our results showed that moringin + α-CD inhibits the production of inflammatory mediators in LPS-stimulated macrophages by down-regulation of pro-inflammatory cytokines (TNF-α and IL-1β), by preventing IκB-α phosphorylation, translocation of the nuclear factor-κB (NF-κB), and also via the suppression of Akt and p38 phosphorylation. In addition, as a consequence of upstream inhibition of the inflammatory pathway following treatment with moringin + α-CD, the modulation of the oxidative stress (results focused on the expression of iNOS and nitrotyrosine) and apoptotic pathway (Bax and Bcl-2) was demonstrated. Therefore, moringin + α-CD appears to be a new relevant helpful tool to use in clinical practice for inflammation-associated disorders.

摘要

在过去几十年中,发现用于预防和治疗炎症性疾病的新化合物的需求日益增长,这促使研究人员将天然产物衍生的药物视为治疗炎症相关疾病的有效选择。本研究的目的是研究辣木衍生的4-(α-L-鼠李糖吡喃糖氧基)苄基异硫氰酸酯与α-环糊精形成的复合物(辣木素+α-CD)对脂多糖(LPS)刺激的RAW 264.7巨噬细胞的抗炎作用,RAW 264.7巨噬细胞是炎症研究中常用的模型。在缓冲/水溶液中,辣木素+α-CD复合物通过形成稳定的包合物体系提高了这种异硫氰酸酯的水溶性和稳定性。我们的结果表明,辣木素+α-CD通过下调促炎细胞因子(TNF-α和IL-1β)、阻止IκB-α磷酸化、核因子-κB(NF-κB)的转位以及抑制Akt和p38磷酸化,抑制LPS刺激的巨噬细胞中炎症介质的产生。此外,在用辣木素+α-CD处理后,炎症途径的上游抑制导致氧化应激(结果集中在iNOS和硝基酪氨酸的表达)和凋亡途径(Bax和Bcl-2)的调节得到证实。因此,辣木素+α-CD似乎是临床实践中用于治疗炎症相关疾病的一种新的有用工具。

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