The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa

Abstract

The antinociceptive and anti-inflammatory activity of caulerpin was investigated. This bisindole alkaloid was isolated from the lipoid extract of Caulerpa racemosa and its structure was identified by spectroscopic methods, including IR and NMR techniques. The pharmacological assays used were the writhing and the hot plate tests, the formalin-induced pain, the capsaicin-induced ear edema and the carrageenan-induced peritonitis. Caulerpin was given orally at a concentration of 100 micromol/kg. In the abdominal constriction test caulerpin showed reduction in the acetic acid-induced nociception at 0.0945 micromol (0.0103-1.0984) and for dypirone it was 0.0426 micromol (0.0092-0.1972). In the hot plate test in vivo the inhibition of nociception by caulerpin (100 micromol/kg, p.o.) was also favorable. This result suggests that this compound exhibits a central activity, without changing the motor activity (seen in the rotarod test). Caulerpin (100 micromol/kg, p.o.) reduced the formalin effects in both phases by 35.4% and 45.6%, respectively. The possible anti-inflammatory activity observed in the second phase in the formalin test of caulerpin (100 micromol/kg, p.o.) was confirmed on the capsaicin-induced ear edema model, where an inhibition of 55.8% was presented. Indeed, it was also observed in the carrageenan-induced peritonitis that caulerpin (100 micromol/kg, p.o.) exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 48.3%. Pharmacological studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive and anti-inflammatory actions and also to identify other active principles present in Caulerpa racemosa.

Keywords: Caulerpa racemosa; anti-inflammatory; antinociceptive; caulerpin.

Figure 1.

Structure of caulerpin (1).

Figure 2.

The antinociceptive effect of caulerpin. Dose–response curves of the caulerpin and dypirone (100, 10, 1, 0.1 and 0.01 μmol/kg, p.o.) on the acetic acid-induced writhing model in mice. Each column represents the mean of six animals. Data are expressed as percentage of inhibition of number writhings.

Figure 3.

The antinociceptive effect of caulerpin on the formalin test. Caulerpin (100 μmol/kg, p.o.) and indomethacin (100 μmol/kg, p.o.), were assayed in the early-phase (0–5 min, panel A) or late-phase (15–30 min, panel B) of the formalin-induced nociception in mice. Each point represents the mean ± S.E.M. of six animals. Statistical differences between the treated and the control groups were evaluated by ANOVA and Dunnett tests and the asterisks denote the significance levels in comparison with control groups, *P < 0.05,**P < 0.01.

Figure 4.

The anti-inflammatory effect of caulerpin. Caulerpin (100 μmol/kg, p.o.) and indomethacin (100 μmol/kg, p.o.) were evaluated on the capsaicin-induced ear edema model. Each column represents the mean ± SEM of five animals. The asterisks denote the significance levels in comparison with control groups, *P < 0.05, **P < 0.01.

Figure 5.

The effect of caulerpin on cell migration. Culerpin (100 μmol/kg, p.o.) and indomethacin (100 μmol/kg, p.o.) were evaluated by the carrageenan-induced peritoneal inflammation test. Each point represents the mean ± S.E.M. of six animals. Statistical differences between the treated and the control groups were evaluated by ANOVA and Dunnett tests and the asterisks denote the significance levels in comparison with control groups, *P < 0.05, **P < 0.01.