Efeitos da Arrabidaea chica (Humb. & Bonpl.) Verlot em osteoartrite.

Abstract

Osteoarthritis (OA) is a disease of great socioeconomic impact, multifactorial and complex, characterized by bone remodeling, synovial inflammation and loss of cartilage, and whose pain is among the main symptoms. It can lead to the individual's disability and functional impairment, and has treatment considered challenging. In this context, the search for alternative therapies for OA is essential, among the possible sources of treatment we highlight medicinal plants. Arrabidaea chica (Humb. & Bonpl.) Verlot is a plant known more popularly as pariri or crajiru, and is present in the National List of Medicinal Plants of Interest to SUS (RENISUS) due to its use in traditional and popular medicine, especially for to treat skin conditions, but also by anti-inflammatory, healing, anti-hypertensive, hepatoprotective, antiparasitic, anti-tumor actions, among others. Thus, highlighting its great pharmacological potential and interest for new scientific investigations. Thus, the objective of this research was to evaluate the anti-inflammatory, anti-nociceptive and regenerative action of A. chica in the control of OA, in addition to its chemical composition. For this, the plant material (leaves of A. chica) was collected, dried at 40 ºC, pulverized, and then soaked in 70% ethyl alcohol under maceration, being subsequently filtered and concentrated in a rotary evaporator at 40 ° C, obtaining it if and the hydroethanolic extract, part of this extract was also subjected to liquid-liquid partition, to obtain the fractions (hexane, butanolic and ethyl acetate) of A. chica. Subsequently, the extract and the fractions obtained were subjected to in vitro analysis, in an inhibition test for cyclooxygenase 1 (COX – 2) and 2 (COX – 2). The extract and fractions also had their effect observed in in vivo studies, in which Rattus norvegicus rats underwent experimental OA induction in the knee, with sodium monoiodoacetate (MIA) - (2 mg / kg), and were treated with hydroethanolic extract of A. chica at doses of 50, 150 and 450 mg / kg, and with hexane, ethyl acetate and butanolic fractions of A. chica, at a dose of 5 mg / kg, administered orally / daily, during 26 days. The animals were clinically evaluated every 7 days, through the activity tests: motor (Rotarod), disability / weight distribution in the paws (Weight Bearing), mechanical hyperalgesia (Randall-Selitto) and mechanical allodynia (Von Frey). On the 29th day, the animals were euthanized and the organs (liver, spleen and kidney) and knees were collected for later histopathological analysis. Chemical analyzes were also carried out by HPLC-MS and CG-MS, to identify the compounds present in the extract and in the hexane fraction of A. chica, these were subjected to in silico testing of molecular docking, targeting COX-2, the in order to guide the choice of the most promising compounds for the treatment of OA. The results obtained showed that the extract and fractions of A. chica inhibit COX – 1 and 2, with the hexane fraction showing the best results, being able to inhibit COX 2 by more than 90%, already at the dose of 10µg / mL and with greater affinity for COX-2 than for COX-1. The extract and fractions of A. chica, also induced significant improvements in the parameters of disability, motor activity, hyperalgesia and allodynia resulting from OA. The extract and fractions also produced improvements in the radiological condition of the knees, however in the histopathological evaluations these improvements were only significant in the treatments with the hexane fractions and ethyl acetate, which obtained, respectively, average scores of 2.9 (± 1.8) and 3.7 (± 1.6), being significantly smaller than the saline group (CTL-), with a mean of 6.0 (± 0.5). It should also be noted that the fractions had excellent results in very low doses, of 5mg / kg. Histopathological analyzes of the liver, spleen and kidney also show that the administered doses of the extract and fractions do not produce toxicity to the animals. As for the chemical composition of the extract, 22 compounds were identified, among which 12 are reported for the first time in this species, most of the identified compounds are important flavonoids, which have great anti-inflammatory potential highlighted in the literature. In silico analyzes suggested the existence of very favorable interactions between some of these flavonoids and the COX – 2 enzyme, mainly for amentoflavone (–9.21 kcal/mol free binding energy), quercetin-O-gallate (free energy of binding of –8.86 kcal / mol) and crisoeriol-O-glucoside (free binding energy of –8.45 kcal/mol). In the hexanic fraction, 20 compounds were identified, being these fatty acids, terpenes and phytosterols, among which we highlight phytol with a major component, which has significant records of analgesic and anti-inflammatory activity. From the molecular docking of these 20 compounds with COX-2, very favorable interactions have also been suggested, between alpha-tocopherol (Vitamin E), scalene and beta-sitosterol, with free binding energies of -10.4, -10.4 and -9.8 kcal / mol, respectively. From these data, it is concluded that the extract and fractions of A. chica have analgesic and anti-inflammatory properties and can be useful for the treatment of OA, and that the activities shown here may be linked to flavonoids, terpenes and phytosterols, which has the potential to intervene in the arachidonic acid pathway, reducing the inflammatory process.