Comparison of anti‐inflammatory activities of ruscogenin,a major steroidal sapogenin from Radix Ophiopogon japonicus,and Its succinylated derivative,RUS‐2HS

Ruscogenin (RUS), first isolated from Ruscus aculeatus, is also a major steroidal sapogenin of the traditional Chinese herb Radix Ophiopogon japonicus. It has robust anti‐inflammatory activities. In previous studies, a ruscogenin affinity column, derived from succinylated ruscogenin (RUS‐2HS), was used to purify an antibody of ruscogenin. A ruscogenin affinity column can also be used to explore its protein targets. However, until now there have been no related pharmacological reports about ruscogenin derivatives. Whether the activity groups of ruscogenin have been blocked during the derivation process remains unknown. The present study was performed to compare the anti‐inflammatory activities in vitro of RUS‐2HS and ruscogenin. Both compounds reduced tumor necrosis factor‐α (TNF‐α)‐induced adhesion of human pro‐myelocytic leukemia cells (HL‐60) to endothelial ECV304 cells with IC₅₀ values of 6.90 nM and 7.45 nM, respectively. They were also inhibited overexpression of ICAM‐1 in ECV304 cells at the mRNA level as evaluated by real‐time PCR and at the protein level evaluated by flow cytometry with similar potency. Such data demonstrate that the functional groups of ruscogenin were not blocked by derivation, suggesting further use of the ruscogenin affinity column for target investigation. Meanwhile, RUS‐2HS was found to have remarkable anti‐inflammatory activity for the first time, indicating it would be a new lead compound with improved bioavailability. Drug Dev Res 69: 196–202, 2008. © 2008 Wiley‐Liss, Inc.