Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone-induced chronic depression model. Swiss female mice, 22-25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+ vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one-way anova, followed by Newman-Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders.
Ethnopharmacological Relevance: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice. Materials & Methods: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action. Results: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects. Conclusion: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.
Major Depressant Disorder is one of the most common neuropsychiatric disorders and affects 17-20% of the world population. Despite scientific efforts, its treatment still presents itself with a limited efficacy and a delayed start-up effect. In this context, natural products are a potential source of new drugs. Riparin I (Rip I), one alcamide isolated from Aniba Riparia, has presented promising results. In pre-clinic trials, it has unchained predictive effects of antidepressant and anxiolytic activities in acute behavioral models of depression and anxiety. Objectives: Facing that, the goal of the trial was to investigate the activity of Riparin I in mice exposed to the model of chronic depression induced by corticosterone (Cort). Methods: Swiss female mice, weighting 22-25g, were divided as the following: control group (vehicle-saline, 1% de tween80, 1% de DMSO, s.c., for 14 and 21 consecutive days), stressed group (CORT, 20mg/kg, s.c, for 14 or 21 days), group treated with RipI (50 mg/kg, orally, for 8 days), group treated with fluvoxamine (Flu 50 mg/kg, orally, for 8 days). Treatments started on the 14th day of corticosterone-induced stress until the 21st day. Behavior models analyzed were as follows: tail suspension (TS) and forced swim test (FS). The corticosterone treated group presented a greater immobility time (IT) than the control group (SC: Cont.: 45 7.30; CONT.: 108.9 3.5; p < 0.01). Meanwhile, the groups treated with RipI (50) and Flu(50) presented a smaller IT than the CORT group (SC: CONT.: 108.93.5; RipI: 49.576.6; Flu: 4213.3; p<0.01). Depressant behavior was unchanged by corticosterone administration and reverted using RipI and Flu. Conclusions: These results allow us to suggest a possible antidepressant effect of RipI in the corticosterone-induced animal depression model.
Exposure to stress in mice and psychosocial stress in humans can alter cognitive functions such as learning and memory, and also be associated with the physiopathology of mood disorders and anxiety. Anxiolytic agents and sedatives nowadays prescribed for the treatment of such illnesses do not cause improvement in cognitive function, and even worsening it, as the benzodiazepines do. In previous studies, Riparins I and III (RipI and RipIII), isolated from Aniba riparia, showed themselves to be affective in animal models predictive of anxiolytic and antidepressant activities, not causing change in hippocratic models. Objectives: Therefore, considering the potential of natural products to the isolation of new drugs, the goal of the present work was to investigate the aspects of RipI and RipIII in the post-stress memory dysfunction caused by repeated injections of corticosterone (CORT). Methods: For that, were used Swiss female mice, weight between 22-25g, divided according to the following experimental groups: Control group (vehiclesaline, 1% de tween80, 1% de DMSO, s.c., for 14 and 21 consecutive days), Stressed group (CORT, 20mg/kg, s.c, for 14 or 21 days), Group treated with RipI or III (50 mg/kg, orally for 8 days), Group treated with fluvoxamine (Flu 50 mg/kg, orally, for 8 days). Treatments occurred beginning the 14th day of corticosterone-induced stress and remained simultaneously with it. Depression was induced with several injections of CORT (20mg/kg, s.c.) beyond the period of 14 days. Behavior models analyzed were open field test and passive avoidance test. Administration of Rips recovered the recent memory of animals to the same level as the control group's (Cont: 249.724.87; Cort: 79.00 45.68; RipI: 3000 ; RipIII: 293.66.429; Flu: 300.0 0 ; p < 0.001). Conclusions: The findings indicate that the repeated administration of RipI and RipIII recovered the memory loss induced by stress and corticosterone in mice.
Introduction:Depression affects approximately 17% of people in the world resulting in enormous personal suffering and economic burden. Despite the advances of antidepressants, the development of new drugs with better efficacy with reduced latency and therapeutic effect of relapses and fewer side effects is needed. Therefore, the search for new drugs based on natural products has grown. The substance named Riparin III (Rip III) has been isolated from an alcamide of the Aniba riparia showing antidepressant effects in preclinical models. Objectives: The aim of this study was to investigate the activity of Rip III in mice submitted to a model of depression induced by corticosterone administration. (CORT). Methods: Swiss female mice were used weighing between 25-30g, divided according to the following experimental groups: controls (vehicle -saline, 1% Tween80, 1% DMSO , sc , for 14 and 21 days in a row), Group with Stress (CORT, 20mg/kg sc for 14 or 21 days), a group treated with RipIII (50 mg/kg, ov for 7 days) group treated with fluvoxamine (Flu) (50 mg / kg, ov for 7 days). Treatments were performed after the 14 th day of corticosterone-induced stress. Depression was induced by repeated injections of CORT (20 mg kg, sc) over 14 days. Behavioral models were evaluated: Forced Swim (FS) and Tail Suspension (TS). The group treated with CORT showed a higher time of immobility (TI) in FS and TS tests compared to controls (TS: Cont.: 45 7.30; CONT.: 108.9 3.5; p < 0.01). While the groups treated with RipIII (50) and Flu (50), presented a smaller TI compared to CORT (TS: CORT.: 108.93.5; RipIII: 33.57 5.97; Flu: 4213.3; p< 0.01). Conclusions:The depressive behavior was triggered by the administration of CORT and reversed by treatment with RipIII and Flu. The results suggest that Rip III triggers a possible antidepressant effect that deserves further investigation.
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