Antinociceptive effect of neo-clerodane diterpenes obtained from Baccharis flabellata
| Autor: | Maria Filomena Garro, A. O. M. María, Rodrigo D. Tosso, José Roberto Cury Saad, Matías Funes, Ricardo D. Enriz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
FURAN NEOCLERODANE Male Phytochemicals Argentina DIENE-ACID CLERODANE DIMER 01 natural sciences Diterpenes Clerodane 03 medical and health sciences Mice Drug Discovery Animals AGONISTS OF KAPPA RECEPTORS Pharmacology Analgesics Plants Medicinal Traditional medicine biology Molecular Structure 010405 organic chemistry Baccharis Plant Extracts Philosophy Ciencias Químicas General Medicine Plant Components Aerial biology.organism_classification 0104 chemical sciences Molecular Docking Simulation 030104 developmental biology Química Orgánica Clerodane Diterpenes BACCHARIS FLABELLATA Female Seasons CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | Fitoterapia. 130 |
| ISSN: | 1873-6971 |
| Popis: | We report here for the first time antinociceptive effects of extracts from Baccharis flabellata. Two extracts in this analysis, one obtained in summer and the other during winter time. Our results indicate that both extract show strong antinociceptive effects, being the extracts obtained during the summer significantly more active. Our results suggest that this activity is mainly due to the presence of the diene-acid clerodane ent-15,16-epoxy-19-hydroxy-1,3,13(16),14-clerodatetraen-18-oic acid (DAC) and its dimer called DACD. Employing naloxone as an antagonist of opioid receptors, we demonstrated that both compounds act on opioid receptors, being the antinociceptive effect of DACD stronger than DAC. Thus, the antinociceptive activity of DACD was almost two times stronger than DAC (44.8 over 24.6 s in the hot-plate test) after one hour of treatments. In order to better understand the mechanism of action at molecular level of these compounds, we conducted a molecular modeling study analyzing the molecular interactions of DAC and DACD complexes with the κ-ORs. Our results suggest interactions for both DAC and DACD with Gln115, Val118, Tyr119, Asn122 and Tyr313 stabilizing their complexes; however, these interactions are significantly stronger for DACD with respect to DAC. This finding could explain why DACD have a higher affinity for the κ-ORs. These results are in agreement with the obtained antinociceptive effect. In addition, our results indicate that these neoclerodanes would have a mechanism of action similar to that of salvinorin A; such information can be very useful for the design of new inhibitors of κ-ORs. Fil: Funes, Matías Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina Fil: Garro, Maria Filomena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina Fil: Maria, Alejandra O.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina Fil: Saad, José Roberto. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina |
| Databáze: | OpenAIRE |
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