生物学中的钙
鱼腥草
信号转导
细胞内
肌醇
受体
哮喘
钙信号传导
药理学
医学
免疫学
细胞生物学
化学
生物
内科学
萃取(化学)
色谱法
作者
Alexis Shiying Huang,Benjamin Chun‐Kit Tong,Harry Chun-Hin Hung,Aston Jiaxi Wu,Olivia Ka-Yi Ho,Anna Hau-Yee Kong,MP Leung,Jing‐Xuan Bai,Xiu‐Qiong Fu,Zhi‐Ling Yu,Min Li,Ting Fan Leung,Judith C.W. Mak,George Pak-Heng Leung,King‐Ho Cheung
标识
DOI:10.1016/j.biopha.2023.114935
摘要
Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca2+) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca2+ signaling is a potential therapeutic strategy for asthma. Houttuynia cordata is a traditional Chinese herb that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that H. cordata might modulate intracellular Ca2+ signaling and could help relieve asthmatic airway remodeling. We found that the mRNA and protein levels of inositol trisphosphate receptors (IP3Rs) were elevated in interleukin-stimulated primary human bronchial smooth muscle cells and a house dust mite-sensitized model of asthma. The upregulation of IP3R expression enhanced intracellular Ca2+ release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with H. cordata essential oil rectified the disruption of Ca2+ signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in H. cordata essential oil because we found similar IP3R suppression in response to the commercially available derivative sodium houttuyfonate. An in silico analysis showed that houttuynin, which downregulates IP3R expression, binds to the IP3 binding domain of IP3R and may mediate a direct inhibitory effect. In summary, our findings suggest that H. cordata is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca2+ signaling.
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