Daphnodorin C isolated from the stems of Daphne kiusiana Miquel attenuates airway inflammation in a mouse model of chronic obstructive pulmonary disease
Daphnodorin C isolated from the stems of Daphne kiusiana Miquel attenuates airway inflammation in a mouse model of chronic obstructive pulmonary disease
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DOI：
10.1016/j.phymed.2021.153848
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发表时间：
2022-01-20
期刊：
影响因子：
7.9
通讯作者：
Lee, Su Ui
中科院分区：
文献类型：
--
作者：
Lee, Jae-Won;Kim, Mun-Ock;Lee, Su Ui
背景：由于长期或大剂量使用慢性阻塞性肺病药物会对慢性阻塞性肺病患者造成不良反应，因此需要更有效、更安全的方法来管理慢性阻塞性肺病症状。毛瑞香 (Daphne kiusiana Miquel) 是一种药用植物，但其抗 COPD 功效研究甚少。 目的：我们研究了从毛瑞香 (Daphne kiusiana Miquel) 中分离出的活性化合物的抗 COPD 活性和分子作用机制，以寻找治疗 COPD 的候选药物。 方法：我们从毛瑞香 (Daphne kiusiana Miquel) 的乙酸乙酯 (EtOAc) 馏分中分离出 7 种化合物 (1-7)，并确定这 7 种化合物可有效控制 PMA 刺激的肺上皮细胞（在体外）和/或使用暴露于香烟烟雾和脂多糖的动物体内的慢性阻塞性肺病模型小鼠。结果：我们表明来自 D. kiusiana 的乙酸乙酯（EtOAc）级分。抑制 PMA 刺激的人肺上皮细胞（体外）和 COPD 模型小鼠（体内）的炎症反应。 EtOAc 组分可有效抑制各种炎症反应，如粘液分泌、ROS 产生、支气管炎症细胞募集以及促炎细胞因子的释放。此外，我们从 EtOAc 馏分中分离出三种具有抗炎功效的化合物，其中瑞香 C 最为有效。最后，我们在体外和体内证明瑞香苷 C 通过抑制 NF-κ B 和特定 MAPK 信号通路（JNK 和 p38）来负调节炎症基因表达。结论：这些结果表明瑞香苷 C 可能是治疗慢性阻塞性肺病症状的一种有前途的治疗替代品。
Background: Since long-term or high-dose use of COPD medication causes adverse effects in patients with COPD, more effective and safer ways to manage COPD symptoms are required. Daphne kiusiana Miquel is a medicinal plant, but its anti-COPD efficacy was little studied.Purpose: We investigated the anti-COPD activity and molecular mechanism of action of active compounds isolated from D. kiusiana to find drug candidates for COPD.Methods: We isolated seven compounds (1-7) in an ethyl acetate (EtOAc) fraction from D. kiusiana, and determined that seven compounds effectively control the inflammatory responsiveness in both PMA-stimulated lung epithelial cells (in vitro) and/or in COPD model mice using cigarette smoke-and lipopolysaccharides-exposed animals in vivo.Results: We show that the ethyl acetate (EtOAc) fraction from D. kiusiana. suppresses inflammatory response in both PMA-stimulated human lung epithelial cells (in vitro) and COPD model mice (in vivo). The EtOAc fraction effectively suppresses various inflammatory responses, such as mucus secretion, ROS production, bronchial recruitment of inflammatory cells, and release of proinflammatory cytokines. Additionally, we isolated three compounds with anti-inflammatory efficacy from the EtOAc fraction, out of which daphnodorin C was the most effective. Finally, we demonstrated that daphnodorin C negatively regulates inflammatory gene expression by suppressing NF-kappa B and specific MAPK signaling pathways (JNK and p38) in vitro and in vivo.Conclusions: These results suggest that daphnodorin C could be a promising therapeutic alternative for managing COPD symptoms.