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通过靶向 NF-B 通路中的 PDK1 发挥抗炎作用。

Exerts Anti-Inflammatory Effects by Targeting PDK1 in the NF-B Pathway.

机构信息

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.

Department of Life Science, Kyonggi University, Suwon 16227, Korea.

出版信息

Am J Chin Med. 2020;48(2):429-444. doi: 10.1142/S0192415X20500226. Epub 2020 Mar 11.

Abstract

Pharmacological activities of some Leguminosae family members were reported. Pharmacological activities of , a Leguminosae family member have never been explored. Therefore, this study investigated anti-inflammatory effects of an methanol extract (Al-ME). In this study, anti-inflammatory effects of Al-ME were investigated in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastritis mice by MTT assay, nitric oxide (NO) production assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter assay, and Western blotting. High-performance liquid chromatography (HPLC) analysis identified ethnopharmacological compounds in Al-ME. Al-ME inhibited NO production without cytotoxicity in peritoneal macrophages and RAW264.7 cells stimulated with LPS or Pam3CSK4. Al-ME downregulated mRNA expression of inflammatory genes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and pro-inflammatory cytokines (tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and IL-6). Al-ME exerted anti-inflammatory activity in LPS-stimulated RAW264.7 cells by inhibiting nuclear factor-kappa B (NF-B) signaling pathway. HPLC analysis identified quercetin, luteolin, and kaempferol as major anti-inflammatory components in Al-ME. Al-ME ameliorated HCl/EtOH-induced gastritis symptoms in mice by suppressing iNOS and IL-6 mRNA expressions and IB phosphorylation. Therefore, these results suggest that Al-ME exhibited anti-inflammatory activity by targeting NF-B signaling pathway, implying that Al-ME could be potent anti-inflammatory medications to prevent and treat inflammatory diseases.

摘要

一些豆科家族成员的药理活性已被报道。豆科家族成员的药理活性从未被探索过。因此,本研究调查了一种甲醇提取物(Al-ME)的抗炎作用。在这项研究中,通过 MTT 测定法、一氧化氮(NO)产生测定法、半定量逆转录-聚合酶链反应(RT-PCR)、荧光素酶报告测定法和 Western blot 分析,研究了 Al-ME 在 LPS 刺激的 RAW264.7 细胞和 HCl/EtOH 诱导的胃炎小鼠中的抗炎作用。高效液相色谱(HPLC)分析鉴定了 Al-ME 中的民族药理学化合物。Al-ME 抑制了 LPS 或 Pam3CSK4 刺激的腹腔巨噬细胞和 RAW264.7 细胞中 NO 的产生,而没有细胞毒性。Al-ME 下调了炎症基因(诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2))和促炎细胞因子(肿瘤坏死因子-(TNF-),白细胞介素-1(IL-1)和 IL-6)的 mRNA 表达。Al-ME 通过抑制核因子-kappa B(NF-B)信号通路在 LPS 刺激的 RAW264.7 细胞中发挥抗炎作用。HPLC 分析鉴定出 Al-ME 中的主要抗炎成分是槲皮素、木犀草素和山奈酚。Al-ME 通过抑制 iNOS 和 IL-6 mRNA 表达和 IB 磷酸化,改善了 HCl/EtOH 诱导的胃炎小鼠的症状。因此,这些结果表明,Al-ME 通过靶向 NF-B 信号通路发挥抗炎作用,表明 Al-ME 可能是预防和治疗炎症性疾病的有效抗炎药物。

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