Biotransformation of asiatic acid by Cunninghamella echinulata and Circinella muscae to discover anti-neuroinflammatory derivatives

In this study, the biotransformation of asiatic acid by Cunninghamella echinulata CGMCC 3.970 and Circinella muscae CGMCC 3.2695 was investigated. Scaled-up biotransformation reactions yielded eight metabolites. Their structures were established based on extensive NMR and HR-ESI-MS data analyses and four of them are new compounds. C. echinulata could catalyze the regioselecitve hydroxylation, carbonylation and lactonization to yield five metabolites. C. muscae could selectively catalyze hydroxylation, acetylation and glycosylation to yield four products. Furthermore, all the identified metabolites were evaluated for their anti-neuroinflammatory activities in LPS-induced BV-2 cells. Most metabolites displayed pronounced inhibitory effect on nitric oxide (NO) production. The results suggested that biotransformed derivatives of asiatic acid might be served as potential neuroinflammatory inhibitors.