stem bark ethanolic extract obtained by sequential pressurized liquid extraction: Chromatographic characterization and profiling of cytotoxic, antitumoral and immunopharmacological properties.

This study aims to characterize the cytotoxic, antitumoral and immunopharmacological profile of the ethanolic extract of (EEHB) stem bark. Chromatographic analysis revealed the major EEHB composition in dimethyl isoplumerideo acid, 13-deoxyplumerido, isoplumeride, and plumeride. Cytotoxicity was performed on MCF-7 and MCF-10A cell lines using MTT assay. The antitumor activity was assessed using sarcoma 180 tumor cells subcutaneously implanted in mice. After seven days, hematological and biochemical analysis, and pathological evaluation of tumors and visceral organs were carried out. The IC value was 28.49 ± 2.05 μg/mL on MCF7 cells, but over 320 μg/mL on MCF-10A cells. Molecular docking was predicted using the caspase 3 molecular target with plumeride and isoplumeride ligands. Both compounds were also analyzed by PreADMET. The tumor growth inhibition was comparable to 5-FU. EEHB reduced the proliferative index (Ki67 immunoexpression) but increased the expression of apoptotic markers in a sarcoma 180 model. The ligands showed interaction with Caspase 3 with a binding energy between -7.2 and -6.6 kcal/mol for isoplumeride and -7.8 to -7.0 kcal/mol for plumeride. Hydrogen interactions were present between the ligands and caspase 3. Both phytochemicals showed low or no permeability in blood-brain barrier and medium permeability in Caco-2 cells and only isoplumeride showed mutagenic potential and carcinogenic. EEHB presented no toxicological effect either on the hematological parameters or average weight and histological features of liver, kidneys, and spleen. Our data suggest that EEHB has antitumor activity in S-180 tumor-bearing mice by blocking cell cycle and increasing apoptosis.