KM Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, the Republic of Korea.
KM Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, the Republic of Korea.
Biomed Pharmacother. 2024 Apr;173:116319. doi: 10.1016/j.biopha.2024.116319. Epub 2024 Feb 28.
Effects of Dictamnus dasycarpus Turcz. on allergic asthma and their underlying mechanisms remain unclarified. Thus, we investigated the effects of D. dasycarpus Turcz. water extract (DDW) on mucus hypersecretion in mice with ovalbumin (OVA)-induced asthma and human bronchial epithelial cells.
BALB/c mice were used to establish an OVA-induced allergic asthma model. Mice were grouped into the OVA sensitization/challenge, 100 and 300 mg/kg DDW treatment, and dexamethasone groups. In mice, cell counts in bronchoalveolar lavage fluid (BALF), serum and BALF analyses, and histopathological lung tissue analyses were performed. Furthermore, we confirmed the basic mechanism in interleukin (IL)-4/IL-13-treated human bronchial epithelial cells through western blotting.
In OVA-induced asthma mice, DDW treatment reduced inflammatory cell number and airway hyperresponsiveness and ameliorated histological changes (immune cell infiltration, mucus secretion, and collagen deposition) in lung tissues and serum total immunoglobulin E levels. DDW treatment lowered BALF IL-4, IL-5, and IL-13 levels; reduced levels of inflammatory mediators, such as thymus- and activation-regulated chemokine, macrophage-derived chemokine, and interferon gamma-induced protein; decreased mucin 5AC (MUC5AC) production; decreased signal transducer and activator of transcription (STAT) 6 and STAT3 expression; and restored forkhead box protein A2 (FOXA2) expression. In IL-4/IL-13-treated human bronchial epithelial cells, DDW treatment inhibited MUC5AC production, suppressed STAT6 and STAT3 expression (related to mucus hypersecretion), and increased FOXA2 expression.
DDW treatment modulates MUC5AC expression and mucus hypersecretion by downregulating STAT6 and STAT3 expression and upregulating FOXA2 expression. These findings provide a novel approach to manage mucus hypersecretion in asthma using DDW.
白鲜皮（Dictamnus dasycarpus Turcz.）对过敏性哮喘的影响及其潜在机制尚不清楚。因此，我们研究了白鲜皮水提取物（DDW）对卵清蛋白（OVA）诱导的哮喘小鼠和人支气管上皮细胞中黏液过度分泌的影响。
使用 BALB/c 小鼠建立 OVA 诱导的过敏性哮喘模型。将小鼠分为 OVA 致敏/激发、100 和 300mg/kg DDW 治疗和地塞米松组。在小鼠中，进行支气管肺泡灌洗液（BALF）、血清和 BALF 分析以及肺组织病理学分析。此外，我们通过 Western blot 确认了白细胞介素（IL）-4/IL-13 处理的人支气管上皮细胞中的基本机制。
在 OVA 诱导的哮喘小鼠中，DDW 治疗降低了炎症细胞数量和气道高反应性，并改善了肺组织和血清总免疫球蛋白 E 水平的组织学变化（免疫细胞浸润、黏液分泌和胶原沉积）。DDW 治疗降低了 BALF 中的 IL-4、IL-5 和 IL-13 水平；降低了炎症介质水平，如胸腺激活调节趋化因子、巨噬细胞衍生趋化因子和干扰素γ诱导蛋白；减少黏蛋白 5AC（MUC5AC）的产生；降低信号转导和转录激活因子（STAT）6 和 STAT3 的表达；并恢复叉头框蛋白 A2（FOXA2）的表达。在 IL-4/IL-13 处理的人支气管上皮细胞中，DDW 治疗抑制 MUC5AC 的产生，抑制 STAT6 和 STAT3 的表达（与黏液过度分泌有关），并增加 FOXA2 的表达。
DDW 通过下调 STAT6 和 STAT3 的表达以及上调 FOXA2 的表达来调节 MUC5AC 的表达和黏液过度分泌。这些发现为使用 DDW 治疗哮喘中的黏液过度分泌提供了一种新方法。
