Ten undescribed derivatives of lithocholic acid produced by biotransformation and their anti-neuroinflammatory...

Ten undescribed hydroxylated, acetylated, esterified and glycoside derivatives of lithocholic acid (LCA) were obtained through the biotransformation of Aspergillus minisclerotigenes, alongside four known compounds. Structural characterization employed integrated NMR spectroscopy, HR-ESI-MS, and X-ray crystallography. Biological evaluation identified compound 10 as a potent inhibitor of LPS-induced NO production in BV2 microglial cells (IC₅₀ = 4.67 μM) and dose-dependently suppressed mRNA expression of IL-1β, TNF-α, iNOS, and COX-2. Furthermore, compound 10 promoted M2-polarization of LPS-activated microglia to attenuate neuroinflammation. Subsequent analysis demonstrated its induction of inflammatory autophagy in BV2 cells. These results suggested that biotransformation was an efficient strategy for structural diversification of LCA and discovery of potent anti-inflammatory leads.