Caracterização química, estudo farmacológico e toxicológico de Siparuna guianensis Aublet. (Siparunaceae)

Abstract

The species Siparuna guianensis Aublet. (Siparunaceae), known as negramina, capitú, folha-santa e limão-bravo, is widely distributed around the national territory. Species have traditionally been used to combat the symptoms of some pathologies fever, inflammation, headaches and body aches, and other disorders. The present study aimed to evaluate the antioxidant, antinociceptive and anti-inflammatory activities and acute oral toxicity profile of the dichloromethane partition (PDCM), as well as to determine the chemical profile of PDCM and its fractions. For this, the dry leaves were subjected to methanol extraction by static maceration. The methanolic extract was subject to liquidliquid partition, firstly with hexane, followed by dichloromethane, to obtain the dichloromethane partition (PDCM). Then, PDCM was fractionated, and 14 fractions (FD1 – FD14) were collected. The PDCM and fractions chemical profiles was performed using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), which allowed the identification of terpenes and flavonoids. According to the in vitro tests, PDCM was effective in reducing the DPPH radical (IC50 25 μg/mL); the value of 0.34 mg/mg of PDCM in ascorbic acid equivalents was determined using the fosfomolybdenium assay; the sample at 7.5 mg was able to inhibit lipid peroxidation with no statistical difference compared to the reference substance (BHT) at the same concentration in the TBA assay. Besides, the in vivo anti-inflammatory activity was investigated in mice by the cróton oil-induced ear edema and by the model of peritonitis induced by LPS. PDCM was capable to reduce the ear edema at 100 and 300 mg/kg by 54% and 52%, respectively. Also, PDCM inhibited the leucocyte migration by 53% at 100 mg/kg. The acute toxicological evaluation, during 14 days, suggested that the oral administration of this sample is safe. PDCM also showed antinociceptive action in two of the three models used. The number of writhing was reduced by 67%, 71% and 83% at 100, 200 and 300 mg/kg, respectively, in acetic acid-induced writhing test. The neurogenic and inflammatory antinociceptive activity was also observed by the formalin test. All doses (100, 200 and 300 mg/kg) were effective, reducing by 56%, 54% e 48% the licking time during the neurogenic inflammation, respectively. All doses (100, 200 and 300 mg/kg) were also effective in the second phase, however in a less significant manner, reducing the licking time by 29%, 38%, and 44%, respectively. Due to the behavioral nature of the antinociceptive assays, the open field test was carried out to ensure that the sample has no interference on animal locomotion. The results indicated that PDCM from S. guianensis is endowed with antioxidant, antinociceptive and antiinflammatory potential, probably related to the terpenes and flavonoids presented in this species.