Biotransformation of oleanonic acid by circinella muscae to produce novel 11,12-epoxy-13,28-lactonized derivatives and their anti-neuroinflammatory activity

Biotransformation of oleanonic acid by Circinella muscae CGMCC 3.2695 yielded two novel 11, 12-epoxidized and 13, 28-lactonized metabolites (compounds 5 and 6) alongside four previously identified compounds. Structural elucidation was conducted through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. The fungus C. muscae demonstrates catalytic capability in mediating the structural transformation of oleanonic acid, facilitating the generation of both 11α, 12α- and 11β, 12β-trimeric oxygen-containing cyclic structures, in addition to producing 13β, 28β-lactone derivatives. Furthermore, the potential anti-neuroinflammatory activity of metabolites was investigated by assessing their ability to inhibit nitric oxide (NO) production in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). Compounds 1, 2, and 6 exhibited significant inhibitory effects, with IC50 values of 25.70, 34.64, and 5.25, respectively. These results suggested that biotransformation derivatives of oleanonic acid might be served as potential neuroinflammatory inhibitors.