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在卵清蛋白诱导的变应性哮喘小鼠模型中,通过调节 NF-κB 信号通路,评估粗茎鳞毛蕨的体内和体外抗变态反应和抗炎作用。

In vivo and in vitro anti‑allergic and anti‑inflammatory effects of Dryopteris crassirhizoma through the modulation of the NF‑ĸB signaling pathway in an ovalbumin‑induced allergic asthma mouse model.

机构信息

Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea.

Faculty of Biology and Environmental Science, University of Science and Education, The University of Danang, Danang 555940, Vietnam.

出版信息

Mol Med Rep. 2020 Nov;22(5):3597-3606. doi: 10.3892/mmr.2020.11460. Epub 2020 Aug 25.

DOI:10.3892/mmr.2020.11460
PMID:33000211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7533436/
Abstract

Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, anti‑influenza virus, anti‑tumor, anti‑reverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)‑induced allergic asthma mouse model and phorbol myristate acetate (PMA)‑ and A23187‑stimulated HMC‑1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL‑10 and interferon (IFN)‑γ) and decreased the levels Th2 cytokines (IL‑4, IL‑5 and IL‑13) and proinflammatory cytokines (IL‑6 and TNF‑α). Furthermore, DC treatment inhibited the activation of NF‑κB signaling (NF‑κB, p‑NF‑κB, IκB and p‑IκB), both in BALF and lung homogenates. Serum levels of total IgE and OVA‑specific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the anti‑inflammatory effect of OVA‑specific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL‑6 and TNF‑α, and the activation of NF‑κB signaling (NF‑κB and p‑NF‑κB), in PMA and calcium ionophore A23187‑stimulated HMC‑1 cells. In summary, the current study demonstrated that DC acts a potent anti‑allergic and anti‑inflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187‑stimulated HMC‑1 cells via NF‑κB signaling in an OVA‑induced allergic asthma model.

摘要

贯众(DC)具有广泛的药理作用,包括抗菌、抗流感病毒、抗肿瘤、抗逆转录酶和抗氧化作用。然而,DC 对过敏性炎症反应的抑制作用尚不清楚;因此,本研究采用实验性卵清蛋白(OVA)诱导的过敏性哮喘小鼠模型和佛波醇肉豆蔻酸酯(PMA)和 A23187 刺激的肥大细胞系 HMC-1 细胞来揭示 DC 调节气道炎症的作用及其可能的机制。通过在第 1 天和第 14 天将 OVA 乳化在铝中使 BALB/c 小鼠致敏,引发过敏性哮喘。此后,在第 15 天至第 26 天,用 DC 或地塞米松(Dex)经口处理小鼠,然后在第 27、28 和 29 天用 OVA 进行攻毒。组织学分析的结果表明,DC 给药减少了支气管肺泡灌洗液(BALF)中炎症细胞的数量,并抑制了肺组织中的嗜酸性粒细胞浸润、黏液产生和胶原沉积。DC 治疗增加了 Th1 细胞因子(IL-10 和干扰素(IFN)-γ)的水平,并降低了 Th2 细胞因子(IL-4、IL-5 和 IL-13)和促炎细胞因子(IL-6 和 TNF-α)的水平。此外,DC 治疗抑制了 NF-κB 信号通路(NF-κB、p-NF-κB、IκB 和 p-IκB)的活化,无论是在 BALF 还是肺匀浆中。与 OVA 处理相比,DC 处理后血清总 IgE、OVA 特异性 IgE 和 IgG1 水平显著降低。然而,OVA 特异性 IgG2a 的抗炎作用在 DC 处理后更高。此外,DC 治疗减弱了 PMA 和钙离子载体 A23187 刺激的 HMC-1 细胞中促炎细胞因子(包括 IL-6 和 TNF-α)的产生和 NF-κB 信号通路(NF-κB 和 p-NF-κB)的激活。综上所述,本研究表明,DC 通过调节 Th1 和 Th2 反应,并通过 NF-κB 信号通路在 OVA 诱导的过敏性哮喘模型中降低 PMA 和 A23187 刺激的 HMC-1 细胞中的过敏性炎症反应,发挥强大的抗过敏和抗炎作用。

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