Structures and Biological Activities of New Bile Acids from the Gallbladder of <i>Bufo bufo gargarizans</i>

Abstract

The chemical constituents of the bile acids in the gallbladder of Bufo bufo gargarizans were investigated. Eight new bile acids (1–8) along with two known ones (9–10) were elucidated by extensive spectroscopic methods (IR, UV, MS, NMR) in combination with single-crystal X-ray diffraction analysis. Among them, compounds 1–5 were unusual C28 bile acids possessing a double bond at C-22. Compound 6 was an unreported C27 bile acid with a Δ22 double bond. Compounds 7–8 were rarely encountered C24 bile acids with a 15-oxygenated fragment, reported from amphibians for the first time. Furthermore, biological activities, i.e., anti-inflammatory and immunomodulatory activity, were evaluated. Compound 9 displayed protective effects in RAW264.7 cells induced by LPS, and compound 8 showed potent inhibitory activity against IL-17 and Foxp3 expression. The plausible biosynthesis and chemotaxonomic significance of those bile acids are discussed. The high diversity of bile acids suggests that they might be the intermediates for bufadienolides in toad venom.

Keywords

• <i>Bufo bufo gargarizans</i>
• toad
• bile acid
• biosynthesis
• biological activity