Neuropharmacology Potential of the Hydroalcoholic Extract from the Leaves of Piper cernuum: Anxiolytic, Hypnotic, and Antidepressant-Like Effects.

Aim: The use of medicinal plants in the treatment of mental illnesses is a reality that accompanies the history of civilizations, and the Piper genus exhibits many species with pharmacologically proven central effects. Then, this study evaluated the neuropharmacological effects of the hydroalcoholic extract from Piper cernuum (HEPC) leaves to validate its uses in folk medicine. Materials and Methods: Primarily Swiss mice (female, 25-30 g) were pretreated with HEPC (50-150 mg/kg, p.o.), vehicle, or the positive control, and submitted to open-field test (OFT), inhibitory avoidance test (IAT), tail suspension test (TST), and forced swim test (FST). Also, mice were exposed to pentylenetetrazol- and strychnine-induced seizure assay, pentobarbital-induced hypnosis test, and elevated plus-maze (EPM). The GABA levels and MAO-A activity were measured in the animal's brain after 15 days of HEPC administration (150 mg/kg, p.o.). Results: Mice pretreated with HEPC (100 and 150 mg/kg) and exposed to pentobarbital presented decreased sleep latency and increased sleep duration (HEPC 150 mg/kg). In EPM, the HEPC (150 mg/kg) increased the frequency of entry and the time of exploration of mice in the open arms. The antidepressant-like properties of HEPC were demonstrated by the decrease in the mice's immobility time when tested in FST and TST. The extract did not show anticonvulsant activity, in addition to not improving the memory parameters of animals (IAT) or interfering with their locomotor activity (OFT). Besides, HEPC administration decreased the MAO-A activity and increased the GABA levels in the animal's brain. Conclusion: HEPC induces sedative-hypnotic, anxiolytic-, and antidepressant-like effects. These neuropharmacological effects of HEPC could be, at least in part, related to the modulation of the GABAergic system and/or MAO-A activity.

Baccharis dracunculifolia DC Hydroalcoholic Extract Improves Intestinal and Hippocampal Inflammation and Decreases Behavioral Changes of Colitis Mice.

The hydroalcoholic extract of B. dracunculifolia (HEBD) and its major compound p-coumaric acid were evaluated against the severity of intestinal inflammation and behavioral changes like depressive and anxious behavior in colitis mice. Colitis was induced in Swiss mice by oral dextran sulfate sodium (DSS) administration for five days. The mice received vehicle (10 ml/kg), HEBD (3, 30, or 300 mg/kg), or p-coumaric acid (15 mg/kg) orally, once a day for twelve days. Behavioral tests were performed on the 11th and 12th days after the beginning of the treatments. Moreover, the colon, cortex, and hippocampus were collected to analyze oxidative and inflammatory parameters. The treatment with HEBD (300 mg/Kg), but not p-coumaric acid, showed decreased disease activity index (DAI) values compared to the vehicle group and partially preserved the villi architecture and mucin levels. Furthermore, the HEBD increased the antioxidant defenses in the colon and hippocampus and reduced the myeloperoxidase activity and IL-6 levels in the colon from colitis mice. Colitis mice treated with HEBD did not show depressive-like behavior in the tail suspension test. HEBD reduced colon inflammation, while it maintains antioxidant defenses and mucin levels in this tissue. It may reduce neuropsychiatric comorbidities associated with colitis through its antioxidant effects.

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Abstract Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid.