Microbial glycosylation of tanshinone IIA by Cunninghamella elegans AS 3.2028

Tanshinone IIA (TIIA) is a natural product with significant anti-atherogenic activities. However, poor water-solubility and low bioavailability hinder its further exploitation as a drug candidate. In this study, microbial transformation of TIIA by Cunninghamella elegans AS 3.2028 was conducted to obtain two new glycosylated derivatives. Their structures were identified as hydroquinone TIIA 11-O-beta-D-glucopyranoside (1) and hydroquinone TIIA 12-O-beta-D-glucopyranoside (2) based on extensive NMR and MS spectral analyses. The solubility of 1 in 50% MeOH-H2O solution was approximately 50-fold that of TIIA, and 1 showed remarkably improved oral absorption in mice. Furthermore, 1 and 2 exhibited similar Nrf2 activation activity to TIIA.