迷迭香酸
哮喘
肠道菌群
药理学
医学
特应性皮炎
TLR4型
人口
免疫学
生物
炎症
生物化学
抗氧化剂
环境卫生
作者
Huihui� Guo,Yanxing Han,Xianglu Rong,Shen Zhang,Haoran Shen,Lingfei Kong,Yanping Guo,Jizhou Li,Binghe Xu,Tianle Gao,Lulu Wang,Tao Cai,Jian‐Dong Jiang
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-04-01
卷期号:126: 155470-155470
标识
DOI:10.1016/j.phymed.2024.155470
摘要
Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
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