Biological properties of aqueous extract and pyranocoumarins obtained from the bark of Brosimum alicastrum tree.

Brosimum alicastrum is a tree used in Mexican traditional medicine for the treatment of several diseases, including uterine cancer. In this study, the cytotoxic activity of aqueous extract of B. alicastrum bark and isolated compounds xanthyletin (1), luvangetin (2), and 8-hydroxyxanthyletin (3) on three human cancer cell lines was determined. Moreover, the biological effects of 8-hydroxyxanthyletin (3) were investigated. The aqueous extract was prepared according to the ethnomedical information reported from the bark. The compounds were purified using chromatographic methods and their structures were elucidated by spectroscopic techniques. The antiproliferative effect of aqueous extract and isolates was determined in three human tumor cell lines: HeLa, A2780, and MSTO-211H, and evaluated by trypan blue exclusion assay. The cell cycle and the mitochondrial transmembrane potential (ΔΨ) were measured by flow cytometry, while Reactive Oxygen Species (ROS) levels were determined using 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe. The effect on the relaxation activity, mediated by topoisomerase I and II, was evaluated by electrophoresis, and docking studies were performed using Autodock 4.2 to analyze the interactions. Aqueous extract of B. alicastrum bark showed significant antiproliferative effect on the evaluated cancer cell lines (IC50 = 1.6, 8.5, and 21.4 μg/ml). Four coumarins were identified in the extract and three of them were also evaluated. A2780 cell line exhibited higher sensitivity against pyranocoumarins with IC50 values ranging from 32 to 47 μmol/l. 8-hydroxyxanthyletin (3) exerts an interesting effect on human topoisomerases I and II, by inhibiting the enzymes at concentrations comparable to those obtained in antiproliferative assay. Moreover, 8-hydroxyxanthyletin (3) arrests the cell cycle at G0/G1 phase and induces in A2780 cells a concentration-dependent increase in ROS levels. The results of molecular docking suggest the participation of the hydroxyl group in the interaction between 8-hydroxyxanthyletin (3) and topoisomerase I and II. This is the first report that demonstrates the cytotoxic activity of the aqueous extract of B. alicastrum bark, and determines the main metabolites. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Lina Barragán-Mendoza, Dalia M Sotelo-García, Lisa Dalla Via, Hortensia Parra-Delgado. Biological properties of aqueous extract and pyranocoumarins obtained from the bark of Brosimum alicastrum tree. Journal of ethnopharmacology. 2022 May 23;290:115128

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PMID: 35196529

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