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  • Guo, Hui-HuiChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)

Alleviation of allergic asthma by rosmarinic acid via gut-lung axis

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Elsevier,2024
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-531641
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-531641URI
  • https://doi.org/10.1016/j.phymed.2024.155470DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 (5HT) 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-NF kappa B mediated pulmonary inflammation and oxidative stress. Conclusions: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiotaderived 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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  • Han, Yan-XingChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)
  • Rong, Xiao-JuanXinjiang Inst Mat Med, Urumqi, Peoples R China. (author)
  • Shen, ZhenChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)
  • Shen, Hao-RanChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)
  • Kong, Ling-FeiState Key Lab Coal Resources & Safe Min, Beijing, Peoples R China.;China Univ Min & Technol, Sch Chem & Environm Engn, Beijing, Peoples R China. (author)
  • Guo, Yun-DanChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)
  • Li, Ji-ZhouRIKEN, iTHEMS, Wako, Saitama, Japan. (author)
  • Xu, Bo,1980-Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)boaxu109 (author)
  • Gao, Tian-LeChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China. (author)
  • Wang, Lu-LuChinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China. (author)
  • Tie, CaiState Key Lab Coal Resources & Safe Min, Beijing, Peoples R China.;China Univ Min & Technol, Sch Chem & Environm Engn, Beijing, Peoples R China. (author)
  • Jiang, Jian-DongChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China.;Chinese Acad Med Sci, Inst Med Biotechnol, Beijing, Peoples R China. (author)
  • Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China.Xinjiang Inst Mat Med, Urumqi, Peoples R China. (creator_code:org_t)

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  • In:Phytomedicine: Elsevier1260944-71131618-095X

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