Avaliação da atividade antinociceptiva do óleo essencial de Annona vepretorum Mart. (Annonaceae) e do complexo de inclusão do ocimeno com β-ciclodextrina em modelo experimental de dor oncológica

Abstract

Medicinal plants and their secondary metabolites represent an important source for the development of new, more effective, and safer therapeutic options for pain management, including pain associated with cancer. In this sense, the central objective of this study was to evaluate the antinociceptive activity of the essential oil of Annona vepretorum (Av-OE) and of the (E)-β-ocimene free and complexed in β-cyclodextrin (β-CD) in an experimental model of cancer pain. The first chapter of the work provides an overview of the chemistry of monoterpenes and drug delivery systems applied to monoterpenes with analgesic potential. The second chapter provides evidence that oral treatment with Av-OE (50 and 100 mg/kg) was able to attenuate the process of hyperalgesia and/or allodynia induced by the presence of tumor in the mice. In addition, it was observed that the animals treated with the dose of 100 mg/kg showed a reduction in edema/paw tumor on the 12th day of observation (0.37 ± 0.02 mL). The last chapter initially describes the process of obtaining and physicochemical characterization of the ocimene inclusion complex in β-CD (ocimene/β-CD), whose results suggested the adequate complexation. It was also demonstrated that there was a decrease in the cytotoxicity of ocimene/β-CD against tumor cell lines (CI50 > 5 μg/mL), non-tumor cell line (CI50 > 5 μg/mL) and Artemia salina larvae (CL50 > 1000 μg/mL) when compared to free ocimene. In contrast, ocimene/β-CD showed greater hemolytic potential in the presence of erythrocytes from Swiss mice (CH50 = 134.3 ± 3.61 μg/mL). A lethal dose 50% (LD50) value greater than 300 mg/kg was estimated when assessing the acute in vivo toxicity of free and complexed ocimene. The administration of free ocimene or ocimene/β-CD (25 and 50 mg/kg) orally in mice with a solid tumor of sarcoma 180 in the right hind paw was able to reduce cancer pain and tumor volume, with possible participation in the modulation of the inflammatory response, since there was a significant increase in the levels of the anti-inflammatory cytokine IL-10 in the serum of animals treated with ocimene (15.98 ± 4.04 pg/mL) when compared with the sham group (6.73 ± 0.43 pg/mL). The evaluation of hematological parameters suggested less toxicity of the ocimene when complexed. Thus, treatment with the essential oil of A. vepretorum or with the inclusion complex containing (E)-β-ocimene and β-CD has antinociceptive activity in mice with solid sarcoma tumor 180.