Pharmacological mechanism underlying the antinociceptive activity of vanillic acid.

Vanillic acid is found at high concentrations in many plants used in traditional medicine. It has been associated with a variety of pharmacologic activities such as carcinogenesis inhibition, apoptosis and inflammation; however, it has become most popular for its pleasant creamy odor. Since there are few reports concerning the antinociceptive activity of this phenolic compound, the aim of this work was to study this activity in in vivo animal models. Vanillic acid was administered by the intraperitoneal route producing a dose-dependent inhibition of the acetic acid-induced writhing response (ED50: 9.3mg/kg). The antinociceptive activity was inhibited by the pretreatment with ondansetron and yohimbine, indicating that the serotoninergic and adrenergic systems could participate in the mechanism underlying the analgesic activity of vanillic acid. This compound was also demonstrated to interact with ASICs (Acid-sensing Ion Channels) as well as with TPRV1, TRPA1, and TRPM8 receptors in vivo. Furthermore, vanillic acid did not interfere with the locomotor function or motor coordination. The plasmatic phenolic content, analyzed by HPLC, showed that its t1/2 and AUC were 0.123h and 1.38µg·h/mL; respectively. In conclusion, vanillic acid might represent a potential therapeutic option for the treatment of pain.

Antinociceptive activity of aqueous extract and isolated compounds of Lithrea molleoides.

ETHNOPHARMACOLOGICAL RELEVANCE: Lithrea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant commonly used in traditional medicine in South America. AIM OF THE STUDY: In the present study, the in vivo antinociceptive effect of L. molleoides' aqueous extract and its isolated compounds has been investigated. MATERIALS AND METHODS: Antinociceptive activity was evaluated through writhing, formalin and hot plate tests in mice. The phytochemical analysis was performed. RESULTS: The extract produced significant inhibition on nociception induced by acetic acid (ED50: 8.7 mg/kg, i.p.) and formalin (ED50: 7.7 mg/kg, i.p.) administered intraperitoneally and also orally. Yohimbine diminished the activity of the extract in the acetic acid test meanwhile haloperidol enhanced its effect. Two majority compounds, shikimic and vanillic acid were active in chemical nociceptive models used in this work, producing the highest inhibition of the writhing response at a dose of 30 mg/kg i.p. (55.4% and 57.1%, respectively) meanwhile at 100 mg/kg p.o. produced a slight response (23.3% and 23.9%, respectively). CONCLUSIONS: These results suggest that L. molleoides' aqueous extract produced antinociception possibly related to the presence of shikimic and vanillic acid. The adrenergic and dopaminergic systems seem to be involved in the mechanism of antinociception of the extract.