title: In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.
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.
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Thaís C
authors.initials: TC
authors.lastname: Lima
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lucarini
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Angelica C
authors.initials: AC
authors.lastname: Volpe
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Carolina Q J
authors.initials: CQJ
authors.lastname: de Andrade
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Alice M P
authors.initials: AMP
authors.lastname: Souza
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Pauletti
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Ana H
authors.initials: AH
authors.lastname: Januário
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Símaro
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café S/N, Ribeirão Preto - SP 14040-903, Brazil.
authors.forename: Jairo K
authors.initials: JK
authors.lastname: Bastos
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Cunha
authors.affiliation: Faculdade de Engenharia de Ilha Solteira, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Av Brasil 56, Ilha Solteira - SP 15385-000, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Borges
authors.affiliation: Faculdade de Engenharia de Ilha Solteira, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Av Brasil 56, Ilha Solteira - SP 15385-000, Brazil.
authors.forename: Rosangela
authors.initials: R
authors.lastname: da Silva Laurentiz
authors.affiliation: Programa de Pós-Graduação em Ciência Animal, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Valéria A
authors.initials: VA
authors.lastname: Conforti
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Renato L T
authors.initials: RLT
authors.lastname: Parreira
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil.
authors.forename: Carly H G
authors.initials: CHG
authors.lastname: Borges
authors.affiliation: Departamento de Quı́mica, Universidade Federal de Santa Catarina, Campus Universitário Trindade, CP 476, Florianópolis - SC 88040-900, Brazil.
authors.forename: Giovanni F
authors.initials: GF
authors.lastname: Caramori
authors.affiliation: Departamento de Quı́mica, Universidade Federal de Santa Catarina, Campus Universitário Trindade, CP 476, Florianópolis - SC 88040-900, Brazil.
authors.forename: Karla F
authors.initials: KF
authors.lastname: Andriani
authors.affiliation: Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira 201, Franca - SP 14404-600, Brazil. Electronic address: marcio.silva@unifran.edu.br.
authors.forename: Márcio L A
authors.initials: MLA
authors.lastname: E Silva
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D003198:Computer Simulation; D051546:Cyclooxygenase 2 / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004149:Dioxoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced; D005663:Furans / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008024:Ligands; D017705:Lignans / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D011136:Polysorbates / Q000494:pharmacology; D017208:Rats, Wistar; D027821:Rutaceae / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052117:Benzodioxoles; D052246:Cyclooxygenase 2 Inhibitors; D003911:Dextrans; D004149:Dioxoles; D005663:Furans; D008024:Ligands; D017705:Lignans; D011136:Polysorbates; C487944:o-benzyl cubebin; C475934:hinokinin; D003533:Cyproheptadine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C433065:cubebin; D015232:Dinoprostone; D015107:4-Butyrolactone; D007213:Indomethacin
keywords: (−)-Cubebin; (−)-Hinokinin; (−)-O-benzylcubebin; Anti-inflammatory activity; Piper cubeba