Cleydson Breno Rodrigues Dos Santos1, Ryan da Silva Ramos2, Brenda Lorena Sánchez Ortiz3, Gabriel Monteiro da Silva4, Silvana Giuliatti4, José Luis Balderas-Lopez5, Andrés Navarrete5, José Carlos Tavares Carvalho6. 1. Laboratório de Pesquisa em Fármacos, Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil; Laboratório de Modelagem e Química Computacional (LMQC), Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil. 2. Laboratório de Modelagem e Química Computacional (LMQC), Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil. 3. Laboratório de Pesquisa em Fármacos, Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil; Programa de Pós-Graduação em Inovação Farmacêutica, Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil. 4. Grupo de Bioinformatica, Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP/RP), Avenida Bandeirantes 3900, Monte Alegre, Ribeirao Preto, Sao Paulo CEP 14049-900, Brazil. 5. Laboratorio de Farmacología de Productos Naturales, Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico. 6. Laboratório de Pesquisa em Fármacos, Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil; Programa de Pós-Graduação em Inovação Farmacêutica, Departamento de Ciências Biológicas e Saúde, Universidade Federal do Amapá (UNIFAP), Rodovia Juscelino Kubitschek, S/N, Campus Marco Zero, Macapá, AP CEP 68903-419, Brazil. Electronic address: farmacos@unifap.br.
Abstract
ETHNOBOTANICAL RELEVANCE: The oil obtained from the fruits of Pterodon emarginatus Vog. (OPe) is used orally and topically, in traditional medicine for some purposes, such as acute and chronic inflammatory states as rheumatoid arthritis. MATERIALS AND METHODS: In this work, the anti-inflammatory activity of the OPe was demonstrated based on several animal models and presented an in silico study based on the 6α,7β-dihydroxy-vouacapan-17β-oic acid (DHVA) majority compound of the OPe to evaluate the interaction this compound, with cyclooxygenase-2 (COX-2) in 4COX (Mus musculus) and 5KIR (Homo sapiens) and molecular dynamics simulation. RESULTS: The OPe (498 mg/kg, p.o) significantly inhibited (p < 0.05, Student t-test) the primary and secondary reactions of arthritis by Freund's Complete Adjuvant (FCA) and in dermatitis induced by croton oil in mice, OPe inhibited peak of edema. In vascular permeability test in rats, the treatment with OPe was able to block the response to PGE2, serotonin, and bradykinin (p < 0.05, Student t-test). In the writhing test in mice, the OPe at doses of 498 and 980 mg/kg (p.o) produced inhibition of 73% and 92%, respectively, and was not significantly effective in the hot plate test. In the evaluation of the potency in relation to gastric injury (gastric ulcer induced by stress) and combined assay in the assessment of anti-inflammatory potency and gastric damage, it was observed that indomethacin (10 mg/kg, p.o.) inhibited carrageenan edema by 51% and produced a higher number of gastric lesions when compared to the group treated with OPe, where only areas of hyperemia were observed, without the occurrence of ulcerative lesion, and which inhibited the edema by 47%. In the in silico study, it was found that the DHVA is capable of binding to two organisms (4COX - Mus musculus and 5KIR - Homo sapiens), however, with higher binding affinity to the organism Homo sapiens. CONCLUSIONS: As expected, all tested ligands were capable of forming hydrogen interactions with residues at their respective binding sites, but the DHVA ligand was capable of creating slightly more hydrogen bonds when docked to either 4COX or 5KIR than the other tested ligands, thus demonstrating the participation of this compound in the anti-inflammatory and antialgic responses observed in the in vivo assays as a COX-2 inhibitor. Therefore, the results obtained support the traditional use of OPe for inflammatory and gastric problems.
ETHNOBOTANICAL RELEVANCE: The oil obtained from the fruits of Pterodon emarginatus Vog. (OPe) is used orally and topically, in traditional medicine for some purposes, such as acute and chronic inflammatory states as rheumatoid arthritis. MATERIALS AND METHODS: In this work, the anti-inflammatory activity of the OPe was demonstrated based on several animal models and presented an in silico study based on the 6α,7β-dihydroxy-vouacapan-17β-oic acid (DHVA) majority compound of the OPe to evaluate the interaction this compound, with cyclooxygenase-2 (COX-2) in 4COX (Mus musculus) and 5KIR (Homo sapiens) and molecular dynamics simulation. RESULTS: The OPe (498 mg/kg, p.o) significantly inhibited (p < 0.05, Student t-test) the primary and secondary reactions of arthritis by Freund's Complete Adjuvant (FCA) and in dermatitis induced by croton oil in mice, OPe inhibited peak of edema. In vascular permeability test in rats, the treatment with OPe was able to block the response to PGE2, serotonin, and bradykinin (p < 0.05, Student t-test). In the writhing test in mice, the OPe at doses of 498 and 980 mg/kg (p.o) produced inhibition of 73% and 92%, respectively, and was not significantly effective in the hot plate test. In the evaluation of the potency in relation to gastric injury (gastric ulcer induced by stress) and combined assay in the assessment of anti-inflammatory potency and gastric damage, it was observed that indomethacin (10 mg/kg, p.o.) inhibited carrageenan edema by 51% and produced a higher number of gastric lesions when compared to the group treated with OPe, where only areas of hyperemia were observed, without the occurrence of ulcerative lesion, and which inhibited the edema by 47%. In the in silico study, it was found that the DHVA is capable of binding to two organisms (4COX - Mus musculus and 5KIR - Homo sapiens), however, with higher binding affinity to the organism Homo sapiens. CONCLUSIONS: As expected, all tested ligands were capable of forming hydrogen interactions with residues at their respective binding sites, but the DHVA ligand was capable of creating slightly more hydrogen bonds when docked to either 4COX or 5KIR than the other tested ligands, thus demonstrating the participation of this compound in the anti-inflammatory and antialgic responses observed in the in vivo assays as a COX-2 inhibitor. Therefore, the results obtained support the traditional use of OPe for inflammatory and gastric problems.
Authors: Josiane V Cruz; Rodolfo B Serafim; Gabriel M da Silva; Silvana Giuliatti; Joaquín M C Rosa; Moysés F Araújo Neto; Franco H A Leite; Carlton A Taft; Carlos H T P da Silva; Cleydson B R Santos Journal: J Mol Model Date: 2018-08-07 Impact factor: 1.810
Authors: Ryan da Silva Ramos; Josivan da Silva Costa; Rai Campos Silva; Glauber Vilhena da Costa; Alex Bruno Lobato Rodrigues; Érica de Menezes Rabelo; Raimundo Nonato Picanço Souto; Carlton Anthony Taft; Carlos Henrique Tomich de Paula da Silva; Joaquín Maria Campos Rosa; Cleydson Breno Rodrigues Dos Santos; Williams Jorge da Cruz Macêdo Journal: Pharmaceuticals (Basel) Date: 2019-01-25
Authors: Janaina de Alcantara Lemos; Anna Eliza M F M Oliveira; Raquel Silva Araujo; Danyelle M Townsend; Lucas Antonio Miranda Ferreira; Andre Luis Branco de Barros Journal: Biomed Pharmacother Date: 2021-09-07 Impact factor: 6.529
Authors: Josivan da Silva Costa; Ryan da Silva Ramos; Karina da Silva Lopes Costa; Davi do Socorro Barros Brasil; Carlos Henrique Tomich de Paula da Silva; Elenilze Figueiredo Batista Ferreira; Rosivaldo Dos Santos Borges; Joaquín María Campos; Williams Jorge da Cruz Macêdo; Cleydson Breno Rodrigues Dos Santos Journal: Molecules Date: 2018-10-29 Impact factor: 4.411
Authors: Mayara Amoras Teles Fujishima; Nayara Dos Santos Raulino da Silva; Ryan da Silva Ramos; Elenilze Figueiredo Batista Ferreira; Kelton Luís Belém Dos Santos; Carlos Henrique Tomich de Paula da Silva; Jocivania Oliveira da Silva; Joaquín Maria Campos Rosa; Cleydson Breno Rodrigues Dos Santos Journal: Pharmaceuticals (Basel) Date: 2018-07-20