Vinpocetine inhibits overt pain-like behavior.

<p>Panel A: mice were treated with vinpocetine (1, 3, 10, and 30 mg/kg, p.o.) or vehicle (saline) 1 h before acetic acid i.p. injection (0.6% v/v, diluted in saline). Panels B-C: mice were treated with vinpocetine (30 mg/kg, p.o.) or vehicle (saline) 1 h before i.p. injection of phenyl-p-benzoquinone (PBQ, 1890 μg/kg in DMSO 2%, v/v, diluted in saline, panel B), or i.pl. injection of formalin (25 μL of 1.5% formalin, v/v in saline, panel C). The cumulative number of writhing was evaluated over 20 min (Panels A-B) and total number of paw flinches (Panel C) were evaluated over 30 min. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared with the saline group; #<i>P</i> < 0.05 compared to the vehicle group; and ^<i>f</i><i>P</i> < 0.05 compared to the vehicle group and the 1 mg/kg vinpocetine dose. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Vinpocetine inhibits carrageenan-induced decrease in antioxidant capacity.

<p>Mice were treated with vinpocetine (30 mg/kg, p.o.) or vehicle 1 h before carrageenan (100μg, 25 μL) i.pl. injection. Paw skin (Panels A and B) and spinal cord (Panels D and E) samples were collected 3 h after carrageenan injection for measurement of ABTS (Panels A and C) and FRAP (Panels B and D) assays. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared with saline group; and ^#<i>P</i> < 0.05 compared with vehicle group. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Vinpocetine inhibits carrageenan-induced NF-κB activation.

<p>Mice were treated with vinpocetine (30 mg/kg, p.o.) or vehicle 1 h before carrageenan i.pl. injection. Paw skin (Panel A) and spinal cord (Panel B) samples were collected 3 h after stimulus injection in lysis buffer, and the NF-κB activation was measured by ELISA, as a ratio of total NF-κB/phosphorylated NF-κB. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared with saline group; and ^#<i>P</i>< 0.05 compared with vehicle group. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Vinpocetine inhibits carrageenan-induced hyperalgesia and myeloperoxidase (MPO) activity.

<p>Mice were treated with vinpocetine (3, 10 or 30 mg/kg, p.o.) or vehicle (saline) 1 h before carrageenan (100 μg, 25 μL) i.pl. injection. Mechanical (Panel A) and thermal (Panel B) hyperalgesia were assessed at indicated time points after carrageenan administration using the electronic von Frey and hot plate tests, respectively. Myeloperoxidase (MPO) activity was determined in samples collected 9 h after carrageenan injection. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared to saline group; ^#<i>P</i> < 0.05 compared with vehicle group; ^<i>f</i><i>P</i> < 0.05 compared with the dose of 3 mg/kg of vinpocetine; and ^<i>ff</i><i>P</i> < 0.05 compared with the doses of 10 and 30 mg/kg of vinpocetine. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Vinpocetine inhibits carrageenan-induced IL-1β and TNF-α production.

<p>Mice were treated with vinpocetine (30 mg/kg, p.o.) or vehicle 1 h before carrageenan i.pl. injection. Paw skin (Panels A and B) and spinal cord (Panels C and D) samples were collected for the determination of IL-1β (Panels A and C) and TNF-α (Panels B and D) production by ELISA, respectively. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared with saline group; and ^#<i>P</i> < 0.05 compared with vehicle group. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Vinpocetine inhibits carrageenan-induced depletion of reduced glutathione (GSH) levels and decreased nitroblue tetrazolium reduction (NBT) activity.

<p>Mice were treated with vinpocetine (30 mg/kg, p.o.) or vehicle 1 h before carrageenan i.pl. injection. Paw skin (Panels A and B) and spinal cord (Panels C and D) samples were collected 3 h after stimulus injection for the determination of GSH levels and NBT reduction. Results are presented as means ± SEM of 6 mice per group per experiment, and are representative of 2 separate experiments. *<i>P</i> < 0.05 compared with saline group; and ^#<i>P</i> < 0.05 compared with vehicle group. One-way ANOVA followed by Tukey’s <i>t</i> test.</p

Quercetin reduces in a dose-dependent manner intense acute swimming-induced muscle mechanical hyperalgesia and did not affect glucose levels, time spent in swimming behavior or immobility behavior during the intense acute swimming session.

<p>Mice received vehicle (2% DMSO in saline) or quercetin (1–30 mg/kg, i.p.) 30 min before plus reinforcements 12 h after the intense acute swimming session. The intensity of muscle mechanical hyperalgesia was evaluated 6–48 h after the intense acute swimming session (Panel A). Glucose plasmatic levels were determined immediately after and 24 h (peak of the hyperalgesia) after the swimming session (Panel B). Time spent in swimming behavior (Panel C) and immobility behavior (Panel D) were measured during the period of 2 h of the intense acute swimming session in quercetin (30 mg/kg, i.p., 30 min before) and vehicle treated groups. Results are presented as intensity of hyperalgesia (Δ reaction, in grams), glucose (mg/dL of plasma), time spent in swimming behavior and immobility behavior in minutes (Panels A-D) (<i>n</i> = 6 mice per group per experiment, representative of two independent experiments). *P<0.05 compared with naïve and sham groups, #P<0.05 compared with vehicle group, **P<0.05 compared with vehicle and 1 mg/kg groups, ##P<0.05 compared with vehicle, 1 and 3 mg/kg groups, ***P<0.05 compared with vehicle, 1, 3 and 10 mg/kg groups (Two-way ANOVA followed by Tukey’s <i>post hoc</i>).</p

Quercetin reduces intense acute swimming-induced increases in plasmatic concentrations of CK and MyoD mRNA expression in the soleus muscle.

<p>Mice were treated with vehicle or quercetin (30 mg/kg, i.p.) 30 min before plus reinforcements 12 h after the intense acute swimming session. At 2 or 24 h after the intense acute swimming session, blood samples were collected for determination of plasmatic levels of CK (Panel A). Samples of the soleus muscle were collected 24 h after the intense acute swimming session for evaluation of MyoD mRNA expression (Panel B). Results are presented as creatine kinase (total) (U/L of plasma) and MyoD mRNA expression (normalized to Gapdh) (<i>n</i> = 6 mice per group per experiment, representative of two independent experiments). *P<0.05 compared to the naïve and sham groups, #P<0.05 compared with vehicle group (One-way ANOVA followed by Tukey’s <i>post hoc</i>).</p

Quercetin reduces intense acute swimming-induced TNF-α, IL-1β and IL-10 production in the soleus muscle, but not in the gastrocnemius muscle.

<p>Mice were treated with vehicle or quercetin (30 mg/kg, i.p.) 30 min before intense acute swimming session. The TNF-α, IL-1β and IL-10 concentration in the soleus (Panel A) and gastrocnemius (Panel B) muscles were quantified immediately after the end of intense acute swimming session by ELISA. Results are presented as picograms (pg) per 100 mg of soleus and gastrocnemius muscles samples (<i>n</i> = 6 mice per group per experiment, representative of two independent experiments). *P<0.05 compared to the naïve and sham groups, #P<0.05 compared with vehicle group (One-way ANOVA followed by Tukey’s <i>post hoc</i>).</p

Quercetin inhibits NFκB activation and induces Nrf2 and HO-1 mRNA expression in the soleus muscle after intense acute swimming.

<p>Mice were treated with vehicle or quercetin (30 mg/kg, i.p.) 30 min before plus reinforcements 12 h after the intense acute swimming session. NFκB activation (total NFκB/phosphorylated NFκB ratio, Panel A), and Nrf2 (Panel B) and HO-1 (Panel C) mRNA expression in the soleus muscle were assessed 24 h after the intense acute swimming session. Results are presented as NFκB activation (total-p65/phosphotrilated-p65 ratio)/mg of soleus muscle, and Nrf2 and HO-1 mRNA expression (normalized to Gapdh) (<i>n</i> = 6 mice per group per experiment, representative of two independent experiments). *P<0.05 compared to the vehicle treated group (One-way ANOVA followed by Tukey’s <i>post hoc</i>).</p