Pharmacological screening of species from the Lippia genus, content in terpenes and phenylpropanoids, and their vasorelaxing effects on human umbilical artery.

BACKGROUND: Naturally occurring bioactive compounds have a plethora of biological effects. OBJECTIVE: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA). METHODS: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 µg/mL and µM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol). Discussion/Results: The reduction corresponded to approximately 100%, except for limonene (80±1.2 %). When evaluating the concentration of the natural product that promotes 50 % relaxation of the HUA contracted by KCL, EC50 values were: 424.3 µg/mL (EOLa); 468.7±6.7 µg/mL (EOLo); 264.2 ± 8.2 µM (citral); 677.8±5.4 µM (limonene); 186.3±6.4 µM (peryl alcohol); 986.4±7.9 µM (eugenol); and 279.1±4.4 µM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency). CONCLUSION: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Pharmacological screening of the phenolic compound caffeic acid using rat aorta, uterus and ileum smooth muscle.

Caffeic acid is a phenolic compound widely found in commonly consumed foods such as pears, apples and coffee, and is pharmacologically known for its antioxidant, anti-inflammatory and anti-asthmatic properties. However, its relaxant activity in the aorta, uterus and ileum smooth muscle has not been investigated. This study aimed to comparatively evaluate the effect of caffeic acid on smooth muscle from different organs (aorta, uterus and ileum), and the contractions of this different organ were induced by different agonists. The organ bath technique was used, where the organs were placed in different cuvettes with 10 mL of Tyrode solution for 1 h to stabilize, then, myometrial, intestinal strip and aortic ring contractions were evoked using different contractile agonists (KCl 60 mM, PHE 0.1 µM, OT 10-2 IU/mL, CCh 10-6 M and BaCl2 0.1-30 mM); increasing concentrations of caffeic acid (0.03-7 mM) were administered in the experimental preparations. In the presence of KCl (60 mM), caffeic acid caused relaxations with the following EC50 values: 2.7 ± 0.26 mM/mL (aorta), 5.7 ± 0.71 mM/mL (uterus) and 2.1 ± 0.39 mM/mL (ileum). When in the presence of different agonists, PHE (0.1 µM) for the aorta, OT (10-2 IU/mL) for the uterus and CCh (10-6 M) for the ileum, caffeic acid caused relaxations with EC50 values of: 2.7 ± 0.31 mM/mL; 2.2 ± 0.34 mM/mL and 2.0 ± 0.28 mM/mL, respectively. The inhibitory effect of caffeic acid on serotonergic (aorta and uterus) and muscarinic receptors (uterus and ileum), as well as its possible involvement with L-type Ca2+ channels, was also observed. This study reports the pharmacological characterization of caffeic acid on smooth muscle from different organs, for which caffeic acid was more potent in the ileum. A diverse understanding of its performance as a possible therapeutic product is attributed to its relaxant effect.

Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.