Do Ji-Hye, Hong Jung Yeon, Jang Ji-Hye, Jeong Kyu-Tae, Kim Seung Hyun, Lee Hye-Ja
Division of Allergy and Chronic Respiratory Diseases, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong 28159, Republic of Korea.
Infectious Disease Inspection Division, Seoul Regional Office, Animal and Plant Quarantine Agency, Cheongju 07670, Republic of Korea.
Nutrients. 2025 Jun 16;17(12):2015. doi: 10.3390/nu17122015.
Asthma, a chronic airway inflammatory disease characterized by bronchial narrowing and caused by an inflammatory response, results in airway obstruction and hyperresponsiveness. Stachydrine (STA), an abundant metabolite found in plants and humans, is recognized for its bioactivity in treating fibrosis, cancer, and inflammation. However, its effects on asthma have not been fully elucidated. We aimed to investigate the ameliorating effects of STA on chronic airway inflammation caused by (house dust mite, HDM). : We used a murine model of HDM-induced airway inflammation to assess the change in metabolite profile by chronic airway inflammation. The mice were challenged with HDM (35 challenges in total) for up to 12 weeks. Serum metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. : HDM exposure increased airway hypersensitivity, immune cell infiltration, cytokine production, goblet cell hyperplasia, collagen deposition, and alpha smooth muscle actin and fibronectin expression. Serum metabolite analysis revealed that STA levels were lower in the mice with HDM-induced chronic inflammation than in the controls. In vitro analyses demonstrated that HDM sensitization increased cytokine production (interleukin [IL]-6 and IL-8) and extracellular signal-regulated kinase (ERK) activity. However, STA treatment reduced HDM-induced IL-6 and IL-8 production and ERK activity. Co-treatment with a mitogen-activated protein kinase (MAPK) inhibitor and STA resulted in a more pronounced reduction in cytokine production and MAPK activity. : These findings suggest that STA, particularly when used in combination with a MAPK inhibitor, effectively suppresses airway inflammation through ERK pathway inhibition, making it a potential therapeutic agent for asthma treatment.
哮喘是一种慢性气道炎症性疾病，其特征为支气管狭窄，由炎症反应引起，会导致气道阻塞和高反应性。水苏碱（STA）是一种在植物和人体中大量存在的代谢产物，因其在治疗纤维化、癌症和炎症方面的生物活性而受到认可。然而，其对哮喘的影响尚未完全阐明。我们旨在研究STA对由屋尘螨（HDM）引起的慢性气道炎症的改善作用。方法：我们使用HDM诱导的气道炎症小鼠模型，通过慢性气道炎症评估代谢物谱的变化。小鼠接受HDM攻击（共35次攻击），持续12周。使用毛细管电泳飞行时间质谱分析血清代谢物。结果：HDM暴露增加了气道高反应性、免疫细胞浸润、细胞因子产生、杯状细胞增生、胶原蛋白沉积以及α平滑肌肌动蛋白和纤连蛋白表达。血清代谢物分析显示，HDM诱导的慢性炎症小鼠的STA水平低于对照组。体外分析表明，HDM致敏增加了细胞因子产生（白细胞介素[IL]-6和IL-8）和细胞外信号调节激酶（ERK）活性。然而，STA处理降低了HDM诱导的IL-6和IL-8产生以及ERK活性。与丝裂原活化蛋白激酶（MAPK）抑制剂和STA联合处理导致细胞因子产生和MAPK活性更显著降低。结论：这些发现表明，STA，特别是与MAPK抑制剂联合使用时，通过抑制ERK途径有效抑制气道炎症，使其成为哮喘治疗的潜在治疗剂。
