Bai Haoyun, Xue Zhuoyin, Zhang Wen, Feng Chaohua, Zhou Zhenqi, Hu Shiling, Zhang Yongjing, Qin Qiaohong, Wu Yuanyuan, Sun Xiuzhen, Zhou Yuhan, Wang Nan
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
Biofactors. 2023 Jan;49(1):140-152. doi: 10.1002/biof.1879. Epub 2022 Jul 21.
Asthma is a heterogeneous disease related to numerous inflammatory cells, among which mast cells play an important role in the early stages of asthma. Therefore, treatment of asthma targeting mast cells is of great research value. α-Asarone is an important anti-inflammatory component of the traditional Chinese medicine Acorus calamus L, which has a variety of medicinal values. To investigate whether α-asarone can alleviate asthma symptoms and its mechanism. In this study, we investigated the effect of α-asarone on mast cell activation in vivo and in vitro. The release of chemokines or cytokines, AHR (airway hyperresponsiveness), and mast cell activation were examined in a mast cell-dependent asthma model. Western blot was performed to determine the underlying pathway. α-Asarone inhibited the degranulation of LAD2 (laboratory allergic disease 2) cells and decreased IL-8, MCP-1, histamine, and TNF-α in vitro. α-Asarone reduced paw swelling and leakage of Evans blue, as well as serum histamine, CCL2, and TNF-α in vivo. In the asthma model, α-asarone showed an inhibitory effect on AHR, inflammation, mast cells activation, infiltration of inflammatory cells, and the release of IL-5 and IL-13 in lung tissue. α-Asarone decreased the levels of phosphorylated JAK2, phosphorylated ERK, and phosphorylated STAT3 induced by C48/80. Our findings suggest that α-asarone alleviates allergic asthma by inhibiting mast cell activation through the ERK/JAK2-STAT3 pathway.
哮喘是一种与多种炎症细胞相关的异质性疾病,其中肥大细胞在哮喘的早期阶段起重要作用。因此,针对肥大细胞的哮喘治疗具有很大的研究价值。α-细辛脑是中药石菖蒲的一种重要抗炎成分,具有多种药用价值。为了研究α-细辛脑是否能缓解哮喘症状及其作用机制。在本研究中,我们研究了α-细辛脑在体内和体外对肥大细胞活化的影响。在肥大细胞依赖性哮喘模型中检测趋化因子或细胞因子的释放、气道高反应性(AHR)和肥大细胞活化情况。采用蛋白质免疫印迹法确定其潜在途径。α-细辛脑在体外抑制了LAD2(实验室变应性疾病2)细胞的脱颗粒,并降低了IL-8、MCP-1、组胺和TNF-α的水平。α-细辛脑在体内减轻了爪肿胀和伊文思蓝渗漏,以及血清组胺、CCL2和TNF-α的水平。在哮喘模型中,α-细辛脑对AHR、炎症、肥大细胞活化、炎症细胞浸润以及肺组织中IL-5和IL-13的释放均有抑制作用。α-细辛脑降低了C48/80诱导的磷酸化JAK2、磷酸化ERK和磷酸化STAT3的水平。我们的研究结果表明,α-细辛脑通过ERK/JAK2-STAT3途径抑制肥大细胞活化来减轻过敏性哮喘。