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Taurocholic Acid and Glycocholic Acid Inhibit Inflammation and Activate Farnesoid X Receptor Expression in LPS-Stimulated Zebrafish and Macrophages
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Taurocholic Acid and Glycocholic Acid Inhibit Inflammation and Activate Farnesoid X Receptor Expression in LPS-Stimulated Zebrafish and Macrophages
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Journal Article
Taurocholic Acid and Glycocholic Acid Inhibit Inflammation and Activate Farnesoid X Receptor Expression in LPS-Stimulated Zebrafish and Macrophages
2023
Overview
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 Calculus bovis 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 Calculus bovis and Babaodan, which could be important quality markers for the future development of Calculus bovis, as well as promising lead compounds in the treatment of overactive immune responses.
Publisher
MDPI AG,MDPI
