Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Research and Business Foundation, Sungkyunkwan University, Suwon 16419, Republic of Korea.
J Ethnopharmacol. 2019 Mar 1;231:1-9. doi: 10.1016/j.jep.2018.11.013. Epub 2018 Nov 8.
Mycetia cauliflora Reinw. (Rubiaceae) has been used as a traditional remedy to ameliorate clinical signs of inflammatory diseases, including pain, inflammation, ulcers, and wounds. Among the Mycetia subfamilies, the molecular and cellular mechanisms of Mycetia longifolia (Rubiaceae) have been studied. However, those of Mycetia cauliflora are not clearly understood. Comprehensive investigation of this plant is necessary to evaluate its potential for ethnopharmacological use.
and methods: The activities of Mycetia cauliflora methanol extract (Mc-ME) on the secretion of inflammatory mediators, the mRNA expression of proinflammatory cytokines, and identification of its molecular targets were elucidated using lipopolysaccharide (LPS)-induced macrophage-like cells. Moreover, the suppressive actions of Mc-ME were examined in an LPS-induced peritonitis mouse model.
At nontoxic concentrations, Mc-ME downregulated the release of nitric oxide (NO), the mRNA expression of inducible nitric oxide synthase (iNOS), and the mRNA expression of interleukin (IL)-1β from LPS-activated RAW264.7 cells. This extract also inhibited the nuclear translocation of p65 and p50 and the phosphorylation of IκBα, IKK, and AKT. Western blot analysis and in vitro kinase assays confirmed that phosphoinositide-dependent kinase-1 (PDK1) is the direct immunopharmacological target of Mc-ME effect. In addition, Mc-ME significantly reduced inflammatory signs in an animal model of acute peritonitis. These effects were associated with decreased NO production and decreased AKT phosphorylation.
Our results suggest that Mc-ME displays anti-inflammatory actions in LPS-treated macrophage-like cells and in an animal model of acute inflammatory disease. These actions are preferentially managed by targeting PDK1 in the nuclear factor (NF)-κB signaling pathway.
Mycetia cauliflora Reinw.（茜草科）已被用作传统疗法，以改善炎症性疾病的临床症状，包括疼痛、炎症、溃疡和伤口。在 Mycetia 亚科中，已经研究了 Mycetia longifolia（茜草科）的分子和细胞机制。然而，Mycetia cauliflora 的机制尚不清楚。全面研究这种植物对于评估其在民族药理学中的应用潜力是必要的。
使用脂多糖（LPS）诱导的巨噬样细胞，阐明了 Mycetia cauliflora 甲醇提取物（Mc-ME）对炎症介质分泌、促炎细胞因子 mRNA 表达以及鉴定其分子靶标的活性。此外，还在 LPS 诱导的腹膜炎小鼠模型中检查了 Mc-ME 的抑制作用。
在非毒性浓度下，Mc-ME 下调了 LPS 激活的 RAW264.7 细胞中一氧化氮（NO）的释放、诱导型一氧化氮合酶（iNOS）的 mRNA 表达和白细胞介素（IL）-1β的 mRNA 表达。该提取物还抑制了 p65 和 p50 的核易位以及 IκBα、IKK 和 AKT 的磷酸化。Western blot 分析和体外激酶测定证实，磷酸肌醇依赖性激酶-1（PDK1）是 Mc-ME 作用的直接免疫药理学靶标。此外，Mc-ME 可显著减轻急性腹膜炎动物模型中的炎症迹象。这些作用与 NO 产生减少和 AKT 磷酸化减少有关。
我们的结果表明，Mc-ME 在 LPS 处理的巨噬样细胞和急性炎症性疾病动物模型中表现出抗炎作用。这些作用主要通过靶向核因子（NF）-κB 信号通路中的 PDK1 来调节。
