Avaliação das atividades anti-inflamatória, antinociceptiva, cicatrizante, sedativa e do potencialtoxicológico do extrato etanólico, frações e subfrações do caule/casca de ctenodon martii benth

Abstract

The study of medicinal plants establishes interdependence between chemistry and medicine, driving the development of new drugs. This field of research is particularly relevant in countries with high biodiversity, such as Brazil, which has scarce scientific studies proving the efficacy and safety of these natural resources. In this context, the plant Ctenodon martii, collected in the Contendas do Sincorá National Forest, in Bahia, showed in “in vivo” studies antinociceptive and anti-inflammatory action, which reinforces its relevance as an object of scientific investigation. Continuing these discoveries, the present study sought to evaluate the anti-inflammatory, antinociceptive, sedative, healing activities and the toxicological potential of the ethanolic extract, as well as of fractions and subfractions of dichloromethane obtained from the stem/bark of C. martii, expanding the understanding of its bioactive properties. The ethanolic extract of the plant stem/bark was partitioned, yielding a dichloromethane fraction, which, using silica chromatography, yielded subfractions D1, D2, D3, D4, and D5. Subsequently, subfraction D2 was subjected to a new subfractionation, using Sephadex column chromatography, yielding D2SS.1, D2SS.2, and D2SS.3. Phytochemical and chromatographic profiles of the fractionated compounds were evaluated by GC-MS. The results obtained had their variations tested for normal distribution and homogeneous variance; values were considered significant when compared at p < 0.05. For bioassays with subfractions and sub-subfractions at a dose of 25 mg/kg, male Balb/c mice were used. The antinociceptive activities compared to the vehicle control group were observed in D2, D3, D4, D5, D2SS1, D2SS.2 and D2SS.3 in the abdominal writhing test with acetic acid; In formalin in the 1st phase by D2, D3, D2SS.2 and D2SS.3, and in the 2nd phase D2, D3, D4, D2SS.2 and D2SS.3; In the Von Frey test there was hypernociception in D2, D3, D2SS.1, D2SS.2 and D2SS.3. Regarding the anti-inflammatory activity compared to the vehicle control, no paw edema was observed in D2, D3, D2SS.2 and D2SS.3; neutrophil recruitment in D2, D3, D4, D2SS.1, D2SS.2 and D2SS.3; nitric oxide production and no vascular extravasation in D2, D3 and D4. D2 and D3 subfractions reduced the production of cytokines TNF-α and IL-1α detected by ELISA and expression of TNF-α, IL-6 and IL-17 determined by qPCR. When evaluating chronic inflammation, Wistar rats were tested with ethanolic extract and compared to vehicle control, there was a reduction in the formation of granulomas and exudate at doses of 25 and 50 mg/kg; excisional wound area decreased at doses of 25 and 12.5 mg/kg, supporting histological findings. In the elevated plus maze test, there were no sedative effects or locomotor deficit. The toxicological potential by DL50, accompanied by hematological and biochemical assays, did not indicate toxicity and lethality. These results reveal that Ctenodon martii is a promising source for the isolation of new bioactive compounds and therapeutic agents, with potential for phytotherapeutic use.