1. In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.
- Author
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Lima TC, Lucarini R, Volpe AC, de Andrade CQJ, Souza AMP, Pauletti PM, Januário AH, Símaro GV, Bastos JK, Cunha WR, Borges A, da Silva Laurentiz R, Conforti VA, Parreira RLT, Borges CHG, Caramori GF, Andriani KF, and E Silva MLA
- Subjects
- 4-Butyrolactone administration & dosage, 4-Butyrolactone chemical synthesis, 4-Butyrolactone chemistry, 4-Butyrolactone pharmacology, Animals, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Benzodioxoles administration & dosage, Benzodioxoles chemical synthesis, Benzodioxoles chemistry, Catalytic Domain, Computer Simulation, Cyclooxygenase 2 chemistry, Cyclooxygenase 2 Inhibitors administration & dosage, Cyclooxygenase 2 Inhibitors chemical synthesis, Cyclooxygenase 2 Inhibitors chemistry, Cyclooxygenase 2 Inhibitors pharmacology, Cyproheptadine pharmacology, Dextrans pharmacology, Dinoprostone pharmacology, Dioxoles administration & dosage, Dioxoles chemical synthesis, Dioxoles chemistry, Edema chemically induced, Furans administration & dosage, Furans chemical synthesis, Furans chemistry, Indomethacin pharmacology, Ligands, Lignans administration & dosage, Lignans chemical synthesis, Lignans chemistry, Lignans isolation & purification, Male, Mice, Molecular Docking Simulation, Polysorbates pharmacology, Rats, Wistar, Rutaceae chemistry, 4-Butyrolactone analogs & derivatives, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Benzodioxoles pharmacology, Dioxoles pharmacology, Furans pharmacology, Lignans pharmacology
- Abstract
(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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