Antinociceptive Activity and Redox Profile of the Monoterpenes (+)-Camphene, p-Cymene, and Geranyl Acetate in Experimental Models

Abstract

Objective. To evaluate antinocicpetive and redox properties of the monoterpenes (+)-camphene, p-cymene, and geranyl acetate in in vivo and in vitro experimental models. Methods. Evaluation of the in vitro antioxidant activity of (+)-camphene, p-cymene, and geranyl acetate using different free radical-generating systems and evaluation of antinociceptive actions by acetic acid-induced writhing and formalin-induced nociception tests in mice. Results. p-Cymene has the strongest antinociceptive effect, but (+)-camphene and geranyl acetate also present significant activity at high doses (200 mg/kg). (+)-Camphene had the strongest antioxidant effect in vitro at TBARS and TRAP/TAR assays and also had the highest scavenging activities against different free radicals, such as hydroxyl and superoxide radicals. Sodium nitroprussiate-derived NO production was enhanced by (+)-camphene. Geranyl acetate and p-cymene also presented some antioxidant effects, but with a varying profile according the free radical-generating system studied. Conclusion. (+)-Camphene, p-cymene, and geranyl acetate may present pharmacological properties related to inflammation and pain-related processes, being potentially useful for development of new therapeutic strategies, with limited possibilities for p-cymene and geranyl acetate.

Figure 1

Chemical structure of (+)-camphene, p-cymene, and geranyl acetate.

Figure 2

Time (s) on the rotarod observed in mice after i.p. treatments. The Statistical differences versus vehicle-treated mice group were calculated using ANOVA, followed by Tukey's test (n = 8, per group), *P < 0.001.

Figure 3

In vitro evaluation of the redox profile of (+)-camphene. (a) TBARS in vitro assay for lipid peroxidation assessment. (b) TRAP and (c) TAR values. (d) Hydroxyl radical-scavenging activity assay. (e) Nitric oxide (NO) scavenging assay. (f) Superoxide dismutase-like (SOD-like) activity. (g) Catalase-like (CAT-like) activity. Vehicle was DMSO 0.1% in all tests; in NO-scavenging activity, SOD-like and CAT-like activity tests, control is DMSO 0.1% alone. Bars represent mean ± SEM values. *P < 0.05, **P < 0.001, ***P < 0.0001 (1-way ANOVA followed by Tukey's post-hoc test).

Figure 4

In vitro evaluation of the redox profile of geranyl acetate. (a) TBARS in vitro assay for lipid peroxidation assessment. (b) TRAP and (c) TAR values. (d) Hydroxyl radical-scavenging activity assay. (e) Nitric oxide (NO) scavenging assay. (f) Superoxide dismutase-like (SOD-like) activity. (g) Catalase-like (CAT-like) activity. Vehicle was DMSO 0.5% in all tests; in NO-scavenging activity, SOD-like, and CAT-like activity tests, control is DMSO 0.5% alone. Bars represent mean ± SEM values. *P < 0.05, **P < 0.001, ***P < 0.0001 (1-way ANOVA followed by Tukey's post-hoc test).

Figure 5

In vitro evaluation of the redox profile of p-cymene. (a) TBARS in vitro assay for lipid peroxidation assessment. (b) TRAP and (c) TAR values. (d) Hydroxyl radical-scavenging activity assay. (e) Nitric oxide (NO) scavenging assay. (f) Superoxide dismutase-like (SOD-like) activity. (g) Catalase-like (CAT-like) activity. Vehicle was DMSO 0.1% in all tests; in NO-scavenging activity, SOD-like and CAT-like activity tests, control is DMSO 0.1% alone. Bars represent mean ± SEM values. *P < 0.05, **P < 0.001, ***P < 0.0001 (1-way ANOVA followed by Tukey's post-hoc test).