Characterization of the Antinociceptive Activity from Stevia serrata Cav

Abstract

Background: Stevia serrata Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action.

Methods: EO was tested in chemical (capsaicin- and glutamate-induced licking response) or thermal (hot plate) models of nociception at 10, 30 or 100 mg/kg doses. The mechanism of action was evaluated using two receptor antagonists (naloxone, atropine) and an enzyme inhibitor (L-NAME). The anti-hyperalgesic effect was evaluated using carrageenan-induced nociception and evaluated in the hot plate.

Results: All three doses of EO reduced licking response induced by glutamate, and higher doses reduced capsaicin-induced licking. EO also increased area under the curve, similar to the morphine-treated group. The antinociceptive effect induced by EO was reversed by pretreatment of mice with naloxone (1 mg/kg, ip), atropine (1 mg/kg, ip) or L-NAME (3 mg/kg, ip). EO also demonstrated an anti-hyperalgesic effect. The 100 mg/kg dose increased the latency time, even at 1 h after oral administration and this effect has been maintained until the 96th hour, post-administration.

Conclusions: Our data suggest that essential oil of S. serrata presents an antinociceptive effect mediated, at least in part, through activation of opioid, cholinergic and nitrergic pathways.

Keywords: Stevia serrata; antinociception; essential oil; inflammation; pain.

Figure 1

Effect of essential oil of Stevia serrata in the capsaicin- and glutamate-induced licking response. The animals have been orally pretreated with the vehicle or essential oil (10, 30, 100 mg/kg) 1 h before the injection of capsaicin (1.6 μg/paw) or glutamate (3.7 ng/paw). Results are expressed as mean ± S.D. (n = 6). Data have been analyzed by ANOVA, followed by Bonferroni post-test, * p < 0.05 has been considered as significant when compared to the vehicle-treated groups.

Figure 2

Effects of essential oil of Stevia serrata and different antagonists in the thermal nociception model (hot plate). The mice were pretreated orally with the vehicle, essential oil (10, 30, 100 mg/kg) or morphine (2.5 mg/kg) and nociceptive effect was evaluated in the hot plate model (A). The animals have been pretreated with naloxone (1 mg/kg, i.p.), atropine (1 mg/kg, i.p.) or L-NAME (3 mg/kg, i.p.) 15 min before oral administration of EO (100 mg/kg) or vehicle (B). Results are expressed as mean ± S.D. (n = 6) of area under the curve calculated by GraphPad Prism Software 5.0. Data have been analyzed by ANOVA, followed by Bonferroni post-test. * p < 0.05 has been considered as significant when compared to the vehicle-treated group and ^# p < 0.05 when comparing with S. serrata-treated group.

Figure 3

Effects of different antagonists on the antinociceptive activity of the essential oil of Stevia serrata in the formalin-induced licking response. Mice received intraperitoneal injection of naloxone (1 mg/kg), atropine (1 mg/kg) or L-NAME (3 mg/kg) 15 min prior to oral administration with the vehicle or essential oil (100 mg/kg). After 60 min, mice received an intraplantar injection of formalin (20 µL, 2.5%). Results are expressed as mean ± S.D. (n = 6). Data have been analyzed by ANOVA, followed by Bonferroni post-test. * p < 0.05 has been considered as significant when compared to the vehicle-treated groups and ^# p < 0.05 when comparing with S. serrata-treated group.

Figure 4

Effect of essential oil of Stevia serrata in the hyperalgesic effect induced by carrageenan. The animals have been pretreated orally with the vehicle or essential oil (10, 30, 100 mg/kg) 1 h before intraplantar injection of carrageenan (1%/paw). Hyperalgesia has been evaluated in the hot plate model. Results are expressed as mean ± S.D. (n = 6). Data have been analyzed by ANOVA, followed by Bonferroni post-test, * p < 0.05 has been considered as significant when compared to the vehicle-treated groups.