Palicourea rigida Kunth (Rubiaceae), also called "bate-caixa" or "douradão", has been used as antihypertensive, antiulcerogenic, anti-inflammatory and analgesic by traditional communities. Pharmacological potential of the ethanol extract from P. rigida (EEPR) and two quercetin derivatives were investigated. Using the high performance liquid chromatography (HPLC) assay, EEPR was analyzed. Phenolic contents (total phenolic and flavonoids) were quantified by spectrophotometric methods. 2,2-diphenyl-1-pycrilhydrazil (DPPH), iron reducing power and β-carotene/linoleic acid bleaching tests were applied to estimate the antoxidant capacity of EEPR. Nociception (acetic acidinduced writhing, formalin and hot plate) and inflammation (carrageenan-induced paw edema and pleurisy) assays were performed. Molecular docking was used to measure the interactions' profiles of ligands (rutin and quercetin) and cyclooxigenases (COX-1 and COX-2). HPLC analysis identified rutin and quercetin derivatives. Expressive levels of total phenolic and flavonoids and a promising antioxidant effect were measured. EEPR, rutin and quercetin reduced the abdominal contortions. EEPR was effective against both phases of formalin, while rutin and quercetin inhibited the second phase. The latency time on hot plate significantly increased after treatment with EEPR. Inflammatory parameters (paw edema, exudate volume and leukocyte infiltrate) were diminished by EEPR, rutin and quercetin. The molecular docking showed that rutin and quercetin are capable of complexing with COX-1 and COX-2 favorably through physical-chemical interactions. The results suggest that EEPR showed a relevant pharmacological potential, which may be related to action of rutin and quercetin derivatives.Key words: Palicourea rigida, rutin, quercetin, antioxidant, antinociception, inflammation.
INTRODUCTIONIn the body, the imbalance between oxidant/antioxidant in favor of the oxidation promotes the oxidative stress that causes proteins, lipids and DNA damages, as well as induces a variety of cellular responses through the generation of reactive oxygen species (ROS) that may be originated from cellular metabolism or environmental sources (Nita and Grzybowski, 2016). ROS have become a concern among researchers because they have been associated with a significant number of diseases involving inflammatory and painful processes that affect humans and animals. In inflammation, for example, ROS cause vascular damage which allows the permeability of macromolecules and inflammatory cells from the blood to tissue (Mittal et al., 2014). This permeability is controlled by vasoactive and chemotactic mediators, which make the inflammatory process active, including the pain (Silva, 2015). Among the mediators that regulate the events of inflammation, vasoactive amines, lipid-derived eicosanoids, cytokines, chemokines and adhesion molecules have been highlighted (Silva, 2015). On the other hand, the inflammatory pain has been treated with non-steroidal anti-inflammatory agents, but present high prevalenc...