Article ; Online: Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.
Phytomedicine : international journal of phytotherapy and phytopharmacology
2024 Volume 126, Page(s) 155470
Abstract: Background: 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 ... ...
| Abstract | Background: 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. Purpose: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods: 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. Results: 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. Conclusions: 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. |
|---|---|
| MeSH term(s) | Humans ; Rosmarinic Acid ; Immunity, Innate ; RNA, Ribosomal, 16S/genetics ; Lipopolysaccharides ; Serotonin ; Lymphocytes ; Asthma/drug therapy ; Asthma/metabolism ; Lung/metabolism ; Fatty Acids, Volatile/metabolism |
| Chemical Substances | Rosmarinic Acid (MQE6XG29YI) ; RNA, Ribosomal, 16S ; Lipopolysaccharides ; Serotonin (333DO1RDJY) ; Fatty Acids, Volatile |
| Language | English |
| Publishing date | 2024-02-20 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 1205240-1 |
| ISSN | 1618-095X ; 0944-7113 |
| ISSN (online) | 1618-095X |
| ISSN | 0944-7113 |
| DOI | 10.1016/j.phymed.2024.155470 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 4115: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.