Vasicine derivatives as potent MAPK inhibitors for psoriasis treatment.

Psoriasis is a common polygenic hereditary skin disease and difficult to cure. Vasicine is an active alkaloid from Chinese herbal medicine Justicia adhatoda L. In present work, we have prepared a series of vasicine derivatives, and anti-inflammatory activities in vitro and in vivo have been evaluated. The in vitro results revealed that derivatives showed good anti-inflammatory activity of inhibiting NO generation. In vivo studies indicated that 4r could alleviate imiquimod induced skin inflammation, reduce the thickness of the epidermis and pathological lesions. Mechanism research showed that 4r could attenuate psoriasis-like skin inflammation via inhibiting MAPK signaling pathway activation, and alleviate LPS-induced inflammation in HaCat cells. Molecular docking study demonstrated that 4r could effectively bind to the active pocket of target MAPK protein 4U3Y and 5J5T. Therefore, vasicine derivatives may be considered as potent MAPK inhibitors for psoriasis treatment.