Triterpenoids from the roots of Sanguisorba officinalis and their Nrf2 stimulation activity

Thirteen undescribed ursane-type triterpenoids, named as sangosides A-M (1-13), including two nor-ursanes, one split ring-ursane and ten ursanes, along with thirty-six known triterpenoids (14-49) were isolated and identified from the roots of Sanguisorba officinalis (Rosaceae). Their structures and absolute configurations were elucidated through spectroscopic data, single-crystal X-ray crystallography and electronic circular dichroism analysis. Their Nrf2 activation activity was evaluated in 293 T cells in vitro. Compounds 2, 5-7, 9-13, 19, 25, 26, 28-39, 41 and 46 showed significant Nrf2 agonistic effects compared with the control group at 25 μM, their cytotoxicity and dose-effect relationship were further studied in a dose-dependent manner. Their structure-activity relationships analysis suggested that the pentacyclic triterpenoids (10, 11, 30-34 and 41) contains two pairs of double bonds on the C & E rings and the ursane-type triterpenoids (25 and 26) with a carbonyl to C-2 and a hydroxyl group at C-3 all showed a considerably Nrf2 activation activity. These results suggested that S. officinalis was worthy of further investigation to find small molecule Nrf2 activators and facilitate their utilization as natural antioxidants.