Antinociceptive Properties of Bergenin

Bergenin (<b>1</b>) is a <i>C</i>-glucoside of 4-<i>O</i>-methylgallic acid with known antiarthritic activity attributed to modulation of cytokine production. The present study was undertaken to evaluate whether <b>1</b> has antinociceptive properties in models of inflammatory pain and to investigate its possible mechanisms of action. Pretreatment with <b>1</b> (12.5–100 mg/kg, ip) produced a dose-related inhibition of acetic acid-induced writhing in mice. Furthermore, treatment with <b>1</b> (50 and 100 mg/kg) inhibited both the early and late phases in a formalin test. In addition, <b>1</b> (50 and 100 mg/kg, ip) inhibited mechanical hyperalgesia, edema, and paw production of hyperalgesic cytokines (TNF-α and IL-1β) induced by complete Freund’s adjuvant. However, the local production of IL-10, an anti-inflammatory cytokine, was not altered by <b>1</b> (100 mg/kg, ip). Treatment with <b>1</b> produced a similar profile of antinociception in wild-type and IL-10-deficient mice. Mice treated with <b>1</b> did not show any motor performance alterations or apparent systemic toxicity. The results presented herein demonstrate that bergenin has consistent antinociceptive and anti-inflammatory properties, acting by the inhibition of IL-1β and TNF-α production, and suggest its potential for the control of inflammatory pain

Effect of ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on vascular permeability using the Evans blue test.

<p>VH is the vehicle group (negative control). The ethanol extract of <i>M</i>. <i>tenuiflora</i> bark was tested at the 100 mg/kg (s.c.) dose. The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of the ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on Cg-induced TNF-α (A) and IL-10 (B) production in the peritoneal exudate.

<p>VH is the vehicle group (negative control). The ethanol extract of <i>M</i>. <i>tenuiflora</i> bark was tested at a dose of 100 mg/kg (s.c.). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of pretreatment of the mice with the hexane (H), DCM (D), ETOAc (E) and BuOH (B) (100 mg/kg) soluble fractions of the <i>M</i>. <i>tenuiflora</i> extract on acetic acid (0.6%)-induced writhing.

<p>VH is the vehicle group (negative control). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on the inhibition of Cg-induced hyperalgesia.

<p>VH is the vehicle group (negative control). The ethanol extract of <i>M</i>. <i>tenuiflora</i> bark was tested at a dose of 100 mg/kg (s.c.). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of the hexane (H) (200 mg/kg) and EtOAc (E) (50 mg/kg) <i>M</i>. <i>tenuiflora</i> bark extract fractions on neutrophil migration to the peritoneal cavity of mice after Cg administration.

<p>VH is the vehicle group (negative control). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effects of ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on the response to nociception induced by intraplantar formalin injection in mice during the neurogenic phase (3A) and inflammatory phase (3B).

<p>Morphine (M, 5 mg/kg, s.c.) and indomethacin (I, 10 mg/kg, i.p.) were the positive control group. VH is the vehicle group (negative control). The ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark was tested at doses of 50, 100 or 200 mg/kg (s.c.). The results are presented as the mean ± S.D. (n = 8) of the number of flinches in the injected paw for a period of 30 min. Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group. # <i>P</i> > 0.05 compared to the indomethacin or morphine—positive control groups.</p

Effect of ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on neutrophil migration into the peritoneal cavity of mice pretreated subcutaneously 30 min prior to Cg injection (500 μg/cavity) to induce peritonitis.

<p>VH is the vehicle group (negative control). The ethanol extract of <i>M</i>. <i>tenuiflora</i> bark was tested at doses of 50, 100 or 200 mg/kg (s.c.). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of the hexane (H), DCM (D), EtOAc (E) and BuOH (B) (100 mg/kg) soluble fractions of <i>M</i>. <i>tenuiflora</i> bark in the Evans blue (A) and Von Frey tests (B).

<p>VH is the vehicle group (negative control). The results are presented as the mean ± S.D. (n = 8). Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p

Effect of the ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark on ICAM-1 expression in the mesentery of mice.

<p>VH is the vehicle group (negative control). The ethanolic extract of <i>M</i>. <i>tenuiflora</i> bark was tested at the dose of 100 mg/kg (s.c.). The results are presented as the mean ± S.D. (n = 8). The optical density of the bands for ICAM-1 was normalized to α-tubulin expression. Statistical significance was calculated by ANOVA followed by Bonferroni's test. *<i>P</i> < 0.05 compared to the vehicle-negative control treated group.</p