Flavanoids derivatives from the root bark of Broussonetia papyrifera as a tyrosinase inhibitor

Abstract Materials developed from Broussonetia papyrifera have been widely used in food and paper industries, but this root bark of the plant has been overlooked despiteits potentially economic values. Thus, the aim of the present study was to develop the root bark of B. papyrifera as a source of bioactive compounds. Chemical investigation of the bark of B. papyrifera led to the isolation of nine flavonoids derivatives ( 1 - 9 ) and two coumarins ( 10 - 11 ), which includes five new compounds ( 1–4 and 11 ). The structures of isolates were elucidated based on spectroscopic analyses. All the isolates were evaluated for their biological effects including tyrosinase inhibition, cytotoxicity, and anti-inflammatory activity. Compound 3 showed inhibition activity against tyrosinase with an IC 50 value of 9.29 μM (positive control, kojic acid: 30.56 μM). Molecular docking was used to support their inhibition activities which indicated that hydrogen bond formation played an important role in the ligand-enzyme complex. In addition, compound 4 exhibited cytotoxic activity against three cancer cell lines (NCI-H1975, HepG2, and MCF-7) and the structure-activity relationship of flavonoids ( 1 - 9 ) were established. Results from anti-inflammatory assay showed that compound 1 inhibited the production of IL-2 in Jurkat cells induced by phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA), with immunosuppressive activity. Overall, our study suggests that flavonoids from root bark of B. papyrifera can be used as a valuable source of bioactive compounds and support its use as a crop benefits to local economic.