Abstract
Supercritical carbon dioxide extracts rich in piperine (SFE) (300 bar; 40 °C) solubilize black pepper (Piper nigrum) bioactive phytochemicals with antitumor effect. The aim of this study was to evaluate pro-oxidant status induced by SFE and its effect against Ehrlich ascites carcinoma in Balb-c mouse. Balb/c mice bearing-Ehrlich ascites carcinoma cells (EAC) (male; 22±2 g) received intraperitoneally SFE (100 mg/kg/d; 9 days) or saline. EAC inhibition/survival, antioxidant enzymes activity and GSH content were evaluated. USCF Chimera 1.11.2 /Autodock Vina 1.1.2 default parameters prepared/docked Glutathione Peroxidase (PDB 2OBI; 1.55 A) and piperine (PubChem CID 638024). SFE inhibit EAC (60%), increasing mice survival (46%) and enhancing activity of superoxide dismutase (4 fold), catalase (56 fold) and glutathione reductase (88%) meanwhile decreased glutatione peroxidase/GPx activity (75%) with GSH depletion (84%). Piperine-GPx poses showed H bonds and hydrophobic interactions near catalytic residues (Cys/Gln/Trp). Therefore, antitumor activity of SFE enhanced EAC pro-oxidative status related with antioxidant enzymes response insufficient to overcome induced oxidative stress. And protein docking suggest the GPx-Piperine interactions could contributed to inhibition of GPx.
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