Anti-inflammatory flavonoids from root bark of Broussonetia papyrifera in LPS-stimulated RAW264.7 cells

Broussonetia papyrifera has been used as a diuretic, tonic and suppressor of edema. Bioactivity-guided fractionation and metabolite investigation of root bark extracts of this plant resulted in the isolation and identification of six 1,3-diphenylpropanes (1, 2, 8, 10, 17, 20), flavanone (3), two chalcones (4, 5), five flavans (6, 11, 14-16), dihydroflavonol (7) and five flavonols (9, 12, 13, 18, 19), including five new compounds (5, 7, 8, 19, 20) that inhibit NO production in LPS-induced RAW264.7 cells. The structures of compounds 1-20 were elucidated on the basis of spectroscopic data (1D and 2D NMR, MS, MS/MS, and HRMS). In particular, compounds 3, 5, 7, 12, and 20 exhibited significant inhibitory effects on the NO, iNOS, and pro-inflammatory cytokine (TNF-alpha and IL-6) production. Therefore, this study suggests that the flavonoid-rich products of B. papyrifera, including the new compounds, could be valuable candidates for the development of pharmaceuticals or functional foods in the prevention and treatment of anti-inflammatory disease.