Carvacrol alleviates CUMS-induced depressive-like behaviors and cognitive impairment by reducing oxidative stress and neuroinflammation in mice.

The present study aimed to evaluate the protective potential of carvacrol against depressive-like behavior and cognitive impairment prompted by chronic unpredictable mild stress (CUMS) in mice. The animals were divided into six groups: Control (non-stressed), CARV (carvacrol at 50 mg/kg, p.o.), FLU (fluoxetine at 10 mg/kg, p.o.), CUMS (stressed), CUMS + CARV and CUMS + FLU, and the groups with CUMS were subjected to different stressors for 28 days. After treatment, mice underwent behavioral testing (open field, forced swimming, sucrose preference, social interaction, novel object recognition and Y-maze) and brain areas were removed for oxidative stress (MDA, nitrite/nitrate and GSH levels) and cytokine (IL-1ß and TNF-α) content assays. The results revealed that CARV administration reversed depressive-like behavior and significantly ameliorated the cognitive deficit induced by CUMS, as well as was able to attenuate oxidative stress (decreased MDA and nitrite/nitrate levels and increased GSH levels). In addition, a significant reduction in hippocampal IL-1ß and TNF-α levels was observed, demonstrating a potential anti-neuroinflammatory activity. Taken together, the antioxidant and anti-inflammatory activities observed in this study indicate that CARV is a promising drug for antidepressant treatment.

Cyclooxygenase-2 inhibitors alleviated depressive and anxious-like behaviors in mice exposed to lipopolysaccharide: Involvement of oxidative stress and neuroinflammation.

Depression and anxiety disorders have their pathophysiologies linked to inflammation and oxidative stress. In this context, celecoxib (CLX) and etoricoxib (ETR) inhibit cyclooxygenase 2 (COX-2), an enzyme expressed by cells involved in the inflammatory process and found in the brain. Studies have been using CLX as a possible drug in the treatment of depression, although its mechanisms at the central nervous system level are not fully elucidated. In this study, the effects of CLX and ETR on behavioral, oxidative, and inflammatory changes induced by systemic exposure to Escherichia coli lipopolysaccharide (LPS) were evaluated in adult male swiss mice. For ten days, the animals received intraperitoneal injections of LPS at 0.5 mg/kg. From the sixth to the tenth day, one hour after LPS exposure, they were treated orally with CLX (15 mg/kg), ETR (10 mg/kg), or fluoxetine (FLU) (20 mg/kg). Twenty-four hours after the last oral administration, the animals underwent evaluation of locomotor activity (open field test), predictive tests for depressive-like behavior (forced swim and tail suspension tests), and anxiolytic-like effect (elevated plus maze and hole board tests). Subsequently, the hippocampus, prefrontal cortex and striatum were dissected for the measurement of oxidative and nitrosative parameters (malondialdehyde, nitrite, and glutathione) and quantification of pro-inflammatory cytokines (IL-1ß and IL-6). LPS induced depressive and anxious-like behavior, and treatment with CLX or ETR was able to reverse most of the behavioral changes. It was evidenced that nitrosative stress and the degree of lipid peroxidation induced by LPS were reduced in different brain areas after treatment with the drugs, as well as the endogenous defense system against free radicals was strengthened. CLX and ETR also significantly reduced LPS-induced cytokine levels. These data are expected to expand information on the role of inflammation in depression and anxiety and provide insights into possible mechanisms of COX-2 inhibitors in psychiatric disorders with a neurobiological basis in inflammation and oxidative stress.

Is Riparin III a promising drug in the treatment for depression?

Stress is crucially related to the pathophysiology of mood disorders, including depression. Since the effectiveness and number of the current pharmacological options still presents significant limitations, research on new substances is paramount. In rodents, several findings have indicated that corticosterone administration induces the manifestation of behavioral and neurochemical aspects of depression. Recently, riparin III has shown antidepressant-like properties in trials performed on animal models. Thus, our goal was to investigate the effects of riparin III on behavioral tests, monoamines levels, oxidative stress and cytokines levels in chronic corticosterone-induced model of depression. To do this, female swiss mice were treated with subcutaneous administration of corticosterone for 22 days. In addition, for the last 10 days, riparin III or fluvoxamine were also administered per os in specific test groups. Control groups received subcutaneous saline injections or distilled water per os. At the end of the timeline, the animals were killed and their hippocampi, prefrontal cortex, and striatum dissected for neurochemical analysis. Brain changes following corticosterone administration were confirmed, and riparin III could reversed the most abnormal behavioral and neurochemical corticosterone-induced alterations. These results suggest the potential antioxidant, anti-inflammatory and antidepressant effects of riparin III after a chronic stress exposure.

The neuroprotective effect of Riparin IV on oxidative stress and neuroinflammation related to chronic stress-induced cognitive impairment.

BACKGROUND: Cognitive impairment is identified as one of the diagnostic criteria for major depressive disorder and can extensively affect the quality of life of patients. Based on these findings, this study aimed to investigate the possible effects of Riparin IV (Rip IV) on cognitive impairment induced by chronic administration of corticosterone in mice. METHODS: Female Swiss mice were divided into four groups: control (Control), corticosterone (Cort), Riparin IV (Cort + Rip IV), and Fluvoxamine (Cort + Flu). Three groups were administered corticosterone (20 mg/kg) subcutaneously during the 22-day study, while the control group received only vehicle. After the 14th day, the groups were administered medications: Riparin IV (Rip IV), fluvoxamine (Flu), or distilled water, by gavage, 1 h after the subcutaneous injections. After treatment, mice underwent behavioral testing, and brain areas were removed for oxidative stress and cytokine content assays. RESULTS: The results revealed that Cort-treated mice developed a cognitive impairment and exhibited a neuroinflammatory profile with an oxidative load and Th1/Th2 cytokine imbalance. Rip IV treatment significantly ameliorated the cognitive deficit induced by Cort and displayed a neuroprotective effect. CONCLUSION: The antidepressant-like ability of Rip IV treatment against chronic Cort-induced stress may be due to its potential to mitigate inflammatory damage and oxidative stress. The antioxidant and anti-inflammatory effect observed indicates Rip IV as a possible drug for antidepressant treatment of non-responsive patients with severe and cognitive symptoms.

Thymol reverses depression-like behaviour and upregulates hippocampal BDNF levels in chronic corticosterone-induced depression model in female mice.

OBJECTIVES: Based on this, the central therapeutic effects of thymol were verified in the neurotrophic pathway. METHODS: Female swiss mice were divided into four groups: control, corticosterone (Cort), thymol (Cort + thymol) and fluvoxamine (Cort + Flu). The administration of corticosterone was used to induce depressive symptoms for 23 days. After the treatment, the animals were exposed the behavioural tests, such as forced swimming test, tail suspension test, sucrose preference test, light/dark test, social interaction test, Y-maze test, plus-maze test and hole-board test. The hippocampus was also removed, and BDNF was measured by ELISA and Western blot. KEY FINDINGS: As a result, thymol and fluvoxamine were able to reverse the depressive symptoms, as well as to improve the anxious frame. The anhedonic and short-term memory was restored with the treatment. In the neurochemical tests, both thymol and fluvoxamine restored BDNF levels, improving the depressive condition. CONCLUSIONS: This work opens up new investigations aiming at the use of this molecule as a therapeutic alternative for treating depression disorders.

Reversal effect of Riparin IV in depression and anxiety caused by corticosterone chronic administration in mice.

Mental disorders have a multifactorial etiology and stress presents as one of the causal factors. In depression, it is suggested that high cortisol concentration contributes directly to the pathology of this disease. Based on that, the study aims to evaluate the potential antidepressant effect of Riparin IV (Rip IV) in mice submitted to chronic stress model by repeated corticosterone administration. Female Swiss mice were selected into four groups: control (Ctrl), corticosterone (Cort), Riparin IV (Cort + Rip IV) and fluvoxamine (Cort + Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20 mg/kg) during twenty-one days, while the control group received only vehicle. After the fourteenth day, groups were administrated tested drugs: Riparin IV, fluvoxamine or distilled water, by gavage, 1 h after subcutaneous injections. After the final treatment, animals were exposed to behavioral models such as forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM) and sucrose preference test (SPT). The hippocampus was also removed for the determination of BDNF levels. Corticosterone treatment altered all parameters in behavioral tests, leading to a depressive- and anxious-like behavior. Riparin IV and fluvoxamine exhibit antidepressant effect in FST, TST and SPT. In EPM and OFT, treatment displayed anxiolytic effect without alteration of locomotor activity. Corticosterone administration decreased BDNF levels and Riparin IV could reestablish them, indicating that its antidepressant effect may be related to ability to ameliorate hippocampal neurogenesis. These findings suggest that Riparin IV improves the depressive and anxious symptoms after chronic stress and could be a new alternative treatment for patients with depression.