Antinociceptive and anti-inflammatory activities of Copaifera pubiflora Benth oleoresin and its major metabolite ent-hardwickiic acid. (10th May 2021)

• Record Type: Journal Article
• Authors: Símaro, Guilherme Venâncio; Lemos, Marivane; Mangabeira da Silva, Jonas Joaquim; Ribeiro, Victor Pena; Arruda, Caroline; Schneider, Ayda Henriques; Wagner de Souza Wanderley, Carlos; Carneiro, Luiza Junqueira; Mariano, Roberta Lopes; Ambrósio, Sérgio Ricardo; Faloni de Andrade, Sérgio; Banderó-Filho, Vilmar C.; Sasse, Astrid; Sheridan, Helen; Andrade e Silva, Márcio Luis; Bastos, Jairo Kenupp
• Is Part Of: Journal of ethnopharmacology. Volume 271(2021)
• Publication Date: 2021-05-10
• Subjects: Anti-inflammatory -- Analgesic -- Copaifera pubiflora -- Copaifera oleoresin -- ent-hardwickiic acid; CPO Copaifera pubiflora oleoresin -- HA ent-hardwickiic acid -- NF-κB nuclear factor kappa B -- IFN-γ interferon-γ -- TNF-α tumor necrosis factorα -- IL-6 interleukin 6 -- IL-10 interleukin 10 -- IL-8 interleukin 8 -- VCAM -1 Vascular cell adhesion protein 1 -- ICAM-1 Intercellular Adhesion Molecule 1 -- IC50 half-maximal inhibitory concentration -- DMSO Dimethyl Sulphoxide -- PMA phorbol-12-myristate-13-acetate -- PBS Phosphate-Buffered Saline -- ELISA enzyme-linked immunosorbent assay -- IL-12p40 interleukin 12p40 -- IL-17 interleukin 17 -- H2O2 hydrogen peroxide -- Nav1.7 voltage-gated sodium channel 1.7 -- LPS lipopolysaccharide -- NO nitric oxide -- EDTA Ethylenediaminetetraacetic acid -- i.p intraperitoneally -- i.p.l intraplantar -- i.a intra-articular -- DNA deoxyribonucleic acid -- HPLC high-performance liquid chromatography -- UV–Vis Ultraviolet and visible -- NMR nuclear magnetic resonance -- GC-MS gas chromatography coupled mass spectrometry -- LC-MS liquid chromatography coupled mass spectrometry; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.113883
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Copaifera species folkloric names are "copaíbas, copaibeiras, copaívas or oil stick", which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce. Aim of the study: To investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent -hardwickiic acid (HA). Material and methods: The phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF- γ, IL-1 β, IL-6, IL-10, and TNF- α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions. Results: In the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p < 0.05). This reduction indicates a decrease in NF- κ B activity. HA and CPO decreased INF- γ, IL-1 β, IL-6, IL-10, and TNF- α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p < 0.05). In experimental arthritis HA significantly decreased joint swelling (p < 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p < 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p < 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p < 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p < 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p < 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect. Conclusions: CPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF- κ B signaling pathway, resulting in anti-inflammatory and antinociceptive activities. Graphical abstract: Image 1