Avaliação das atividades antinociceptiva, anti-inflamatória, antioxidante e antitumoral da associação de β-cariofileno e ácido docosahexanóico em modelos experimentais

Abstract

Introduction: Inflammation is a complex biological response, caused by trauma, infections, immunological reactions or the presence of a foreign body, which involves the immune, autonomic, vascular and somatosensory systems and courses with the synthesis of inflammatory mediators and induction of pain by activating nociceptors. Natural products have been evaluated in this context as a therapeutic alternative in the fight against various inflammatory and infectious diseases and neoplasms. Among them, the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as Docosahexaenoic acid (DHA) stand out. Objective: To evaluate the antinociceptive, anti-inflammatory, antioxidate and antitumor activities of the BCP-DHA association in experimental models. Materials and methods: For that, the antinociceptive effects were evaluated in animal models through the tests of abdominal writhing induced by acetic acid (AC), paw edema induced by intraplantar injection of formalin (F) and Von Frey hypernociception (VF). To determine the anti inflammatory effects, monocytes isolated from peripheral blood of participating adult males were infected with methicillin-resistant Staphylococcus aureus and incubated with treatment for subsequent cytokine measurement and gene expression analysis. The antioxidant capacity was evaluated by the DPPH method. The cytotoxicity assay was carried out to determine the cell viability of malignant (A549) and normal (BEAS-2B) lung strains against treatment with BCP-DHA, and then adhesion and cell migration tests were performed, as well as analysis of gene expression with the doses of the associations determined in the previous test. Statistical analysis was performed using the GraphPad Prisma 6.0 software, considering p<0.05. Results: Antinociceptive effects were observed in the three tests performed (AC, F, VF) when comparing the control (saline) and BCP-DHA treated groups, obtaining statistical significance (p < 0.05). There was a significant reduction in the levels of GM-CSF, TNFα, IL-1β, IL-6 and IL 12, as well as an increase in IL-10 in the groups submitted to treatment with the BCP DHA association, as well as negative regulation of the expression of genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3 and TYK2) in all groups that received treatment, regardless of the presence of infection. In the DPPH test, only BCP showed significant scavenging of free radicals, with EC 50 = 2.82 ± 0.06 M. There was significant cytotoxic activity of the 2 combinations of BCP-DHA tested on A549 tumor cell line, as well as important inhibition of cell adhesion and migration processes. There was an underexpression of genes involved in the cell cycle, DNA repair, nucleotide excision, mismatched bases and post replication, maintenance of telomeres, oncogenes and tumor suppressors, suggesting an important effect on the cell cycle of tumor cells. Therefore, our results strongly infer that the association of BCP-DHA appears as a possible new therapeutic alternative with analgesic, anti inflammatory, pro-apoptotic and antiproliferative effects.