Fig 2: Pristimerin prevents the paclitaxel-induced increase in MAGL activity in the paw skin of female BALB/c mice. (A) Relative fluorescence units (360/460 nm) over time as a product of MAGL-specific signal per mg of the paw skin samples from vehicle-, paclitaxel plus vehicle- and paclitaxel plus pristimerin-treated mice at day 7 post-first injection (dpi) of paclitaxel. Each symbol represents the mean ± SEM of values obtained from 3 experiments from samples pooled from 4 animals. *p < 0.05, **p < 0.01 compared to mice treated with vehicle only (two-way repeated measures ANOVA followed by Tukey’s multiple comparisons test). (B) Area under the curve of relative fluorescence of MAGL-specific signal per mg of the paw skin samples from vehicle-, paclitaxel plus vehicle- and paclitaxel plus pristimerin-treated mice at day 7 dpi of paclitaxel. Each symbol represents the mean ± SEM of values obtained from 3 experiments from samples pooled from 4 animals. **p < 0.01 compared to mice treated with vehicle only and ##p < 0.01 compared to mice treated with paclitaxel + vehicle (one-way ANOVA followed by Tukey’s multiple comparisons test).

Fig 3: Inhibitory effects of various concentrations of betulinic acid, cucurbitacin B, euphol, pristimerin and JZL195 on human recombinant MAGL after 10 min of incubation. Each point represents the mean ± SEM of values obtained from 3 to 5 experiments.

Fig 4: Inhibitory effects of 1 µM betulinic acid, cucurbitacin B, euphol, pristimerin and JZL195 on human recombinant MAGL activity over time. Each point represents the mean ± SEM of values obtained from 3 experiments. *p < 0.05, **p < 0.01 compared to drug vehicle at the same time after treatment (two-way repeated measures ANOVA followed by Dunnett’s multiple comparisons test).