Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheong-ju si, Chungcheongbuk-do, 28116, South Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheong-ju si, Chungcheongbuk-do, 28116, South Korea; Department of Biomolecular Science, University of Science & Technology (UST), Daejeon 341113, South Korea.
Phytomedicine. 2021 Jan;80:153392. doi: 10.1016/j.phymed.2020.153392. Epub 2020 Oct 20.
BACKGROUND: Acacetin 7-O-β-D-glucoside (tilianin) is a major constituent of Agastache rugosa, a traditional medicine that has long been used for the treatment of gastrointestinal disorders. Tilianin has a wide variety of pharmacological properties such as cardioprotective, neuroprotective, and anti-atherogenic activities. We recently discovered that tilianin has the ability to suppress MUC5AC expression in vitro. In addition, we have established an in vivo model of allergic asthma using house dust mite (HDM) that can be applied to tilianin. PURPOSE: We investigated the effects of tilianin on airway inflammation in a HDM-induced asthma mouse model and associated mechanisms. METHODS: Tilianin was treated in splenocytes cultured in Th0 condition and HDM-stimulated bone marrow-derived dendritic cells (BMDCs), and their mRNA expression and cytokines production were determined by quantitative real-time PCR and ELISA. To evaluate the effects of tilianin in an allergic asthma model, mice were sensitized and challenged with HDM. Tilianin was administered prior to challenge by oral gavage and airway hyper-reactivity (AHR) to methacholine, inflammatory cell infiltration, cytokine levels, and airway remodeling were assessed. RESULTS: Tilianin inhibited the production of Th2-related cytokines in splenocytes, which play pivotal roles in allergic airway inflammation. When treated in HDM-stimulated BMDCs, tilianin decreased Th2-skewing cytokine IL-33 and transcription factor IRF4. On the contrary, tilianin increased Th1-skewing regulators, IL-12 and IRF1. In an HDM-induced asthmatic mouse model, tilianin attenuated AHR and airway inflammation. Tilianin suppressed the expression of Th2-related cytokines, IL-13 and IL-33 in lung tissues. As seen in HDM-stimulated BMDCs, tilianin also downregulated the expression of the transcription factor IRF4 but not IRF1. CONCLUSION: Taken together, these results suggest that tilianin attenuates HDM-induced allergic airway inflammation by inhibiting Th2-mediated inflammation through the selective inhibition of the IRF4-IL-33 axis in dendritic cells.
背景：阿克替宁可 7-O-β-D-葡萄糖苷（川陈皮素）是一种传统药物Agastache rugosa 的主要成分，长期以来一直用于治疗胃肠道疾病。川陈皮素具有广泛的药理作用，如心脏保护、神经保护和抗动脉粥样硬化作用。我们最近发现，川陈皮素有抑制体外 MUC5AC 表达的能力。此外，我们已经建立了一种可以应用于川陈皮素的尘螨（HDM）诱导的过敏性哮喘体内模型。 目的：我们研究了川陈皮素对 HDM 诱导的哮喘小鼠模型中气道炎症的影响及其相关机制。 方法：川陈皮素在 Th0 条件下培养的脾细胞和 HDM 刺激的骨髓来源树突状细胞（BMDC）中进行处理，通过定量实时 PCR 和 ELISA 测定其 mRNA 表达和细胞因子产生。为了评估川陈皮素在过敏性哮喘模型中的作用，用 HDM 对小鼠进行致敏和激发。在激发前通过口服灌胃给予川陈皮素，并评估气道高反应性（AHR）、炎性细胞浸润、细胞因子水平和气道重塑。 结果：川陈皮素抑制了在过敏性气道炎症中起关键作用的脾细胞中 Th2 相关细胞因子的产生。当在 HDM 刺激的 BMDC 中处理时，川陈皮素降低了 Th2 偏向细胞因子 IL-33 和转录因子 IRF4。相反，川陈皮素增加了 Th1 偏向调节剂 IL-12 和 IRF1。在 HDM 诱导的哮喘小鼠模型中，川陈皮素减轻了 AHR 和气道炎症。川陈皮素抑制了肺组织中 Th2 相关细胞因子 IL-13 和 IL-33 的表达。与 HDM 刺激的 BMDC 一样，川陈皮素也下调了转录因子 IRF4 的表达，但不影响 IRF1。 结论：综上所述，这些结果表明，川陈皮素通过选择性抑制树突状细胞中的 IRF4-IL-33 轴，抑制 Th2 介导的炎症，从而减轻 HDM 诱导的过敏性气道炎症。
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