Taurocholic Acid and Glycocholic Acid Inhibit Inflammation and Activate Farnesoid X Receptor Expression in LPS-Stimulated Zebrafish and Macrophages

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-02, Vol.28 (5), p.2005
• Main Authors: Ge, Xutao, Huang, Shaoze, Ren, Can, Zhao, Lu
• Format: Article
• Language: English
• Subjects: Acids; Animal genetic engineering; Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Bacterial infections; Bile; Bile acids; Bile Acids and Salts - pharmacology; Biomarkers; Calculus bovis; Chemokines; Chromatography; Cytokine storm; Cytokines; Cytokines - metabolism; farnesoid X receptor; glycocholic acid; Glycocholic Acid - pharmacology; Health aspects; Immune response; Immune system; Immunomodulation; In vivo methods and tests; Infections; Inflammation; Lead compounds; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophages; Mass spectrometry; Mass spectroscopy; Mice; mRNA; Natural products; Scientific imaging; Severe acute respiratory syndrome coronavirus 2; Taurocholic Acid; Tumor necrosis factor-TNF; Zebrafish; Zebrafish - metabolism
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28052005

A hyperactive immune response can be observed in patients with bacterial or viral infection, which may lead to the overproduction of proinflammatory cytokines, or "cytokine storm", and a poor clinical outcome. Extensive research efforts have been devoted to the discovery of effective immune modulators, yet the therapeutic options are still very limited. Here, we focused on the clinically indicated anti-inflammatory natural product and its related patent drug Babaodan to investigate the major active molecules in the medicinal mixture. Combined with high-resolution mass spectrometry, transgenic zebrafish-based phenotypic screening, and mouse macrophage models, taurochiolic acid (TCA) and glycoholic acid (GCA) were identified as two naturally derived anti-inflammatory agents with high efficacy and safety. Both bile acids significantly inhibited the lipopolysaccharide-induced macrophage recruitment and the secretion of proinflammatory cytokines/chemokines in in vivo and in vitro models. Further studies identified strongly increased expression of the farnesoid X receptor at both the mRNA and protein levels upon the administration of TCA or GCA, which may be essential for mediating the anti-inflammatory effects of the two bile acids. In conclusion, we identified TCA and GCA as two major anti-inflammatory compounds in and Babaodan, which could be important quality markers for the future development of , as well as promising lead compounds in the treatment of overactive immune responses.