Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice

Ethnopharmacological relevance: Tabernaemontana catharinensis (Apocynaceae) is a medicinal plant used for the treatment of painful and inflammatory disorders. Here, we investigated the antinociceptive potential of the ethyl acetate fraction (Eta) from T. catharinensis leaves and assessed its toxic effects in mice to validate its popular use. Materials and methods: Adult male Swiss mice (30-35 g) were used. The Eta antinociceptive effect (200-800 mg/kg, oral route (p.o.)) was evaluated in the acetic acid, formalin, capsaicin and tail-immersion tests. Adverse effects were analyzed using rotarod and open-field tests, body temperature, biochemical analysis and gastric lesions assessment. To evaluate the acute (OECD 423) or sub-acute (OECD 407) toxicity of the Eta, it was administered orally at a single (2000 mg/kg) or repeated doses (100-400 mg/kg/day for 28 days), respectively. Mortality, behavioral changes, biochemical and hematological parameters were evaluated. The Eta effect on cellular viability also was evaluated. Results: Eta (200-800 mg/kg) inhibited the nociception caused by acetic acid (93.9 +/- 1.5%), formalin (86.2 +/- 10.8%) or capsaicin (75.4 +/- 3.3%) without inducing gastric lesions. Moreover, Eta neither altered the body temperature, biochemical parameters, nor forced or spontaneous locomotor activity of mice. The acute administration of the Eta (2000 mg/kg) promoted a decrease in blood glucose levels and alanine aminotransferase activity. In the sub-acute toxicity study, Eta increased the aspartate aminotransferase activity (400 mg/kg) and platelet distribution width (200 mg/kg). Furthermore, Eta did not alter the cellular viability in cortical slices. Conclusions: Eta presents antinociceptive effects and mild toxicity in mice. These results support its traditional use as a potential analgesic. (C) 2016 Elsevier Ireland Ltd. All rights reserved.