Oxydative stress, anxiety and depression are associated with changes in cytokine levels. Natural products, including individual and combined plant extracts, have the potential to be used in the treatment of neuropsychiatric disorders. The goal of this study is to investigate the effects of two combined plant extracts, rich in flavonoids, on the levels of the cytokines TNF-α, IL-6, and IL-10 in rats subjected to models of acute cold stress and chronic unpredictable stress. The study utilized common medicinal plants such as Valeriana officinalis, Melissa officinalis, Crataegus monogyna, Hypericum perforatum, and Serratula coronata, which were combined in two unique combinations—Antistress I and Antistress II. The compositions of the used extracts were determined by HPLC methods. Pro- and anti-inflammatory cytokines in rats’ serum were measured with Enzyme-linked immunosorbent assay. The results from the acute stress model revealed that the individual extract of Crataegus monogyna decreased levels of TNF-α, while Serratula coronata, Hypericum perforatum, and Valeriana officinalis effectively reduced IL-6 levels. Both combinations, Antistress I and Antistress II, were effective in reducing TNF-α and IL-6 levels, with Antistress II also increasing IL-10 levels. In the chronic stress model, Hypericum perforatum extract decreased the levels of the pro-inflammatory cytokines TNF-α and IL-6, whereas extracts of Serratula coronata and Valeriana officinalis only reduced TNF-α levels. The two combined extracts, Antistress I and Antistress II, decreased TNF-α and IL-6 levels, while Antistress I also reduced the levels of the anti-inflammatory cytokine IL-10. The combinations of plant extracts used in our experiment have not been previously studied or documented in the available literature. However, based on our own experimental results, we can draw the conclusion that the combinations exhibit a more pronounced effect in reducing cytokine levels compared to the individual plant extracts.

Background: Anxiety disorders are an important not only medical, but also social problem, affecting approx. 300 million people worldwide in 2019. Medications used in the treatment of anxiety are associated with many adverse reactions, which explains the increased use of herbal products as anxiolytics. Methods: An anxiolytic activity of Satureja montana, rosmarinic acid and carvacrol after 14-day long administration on an animal model of acute stress was studied. For measurement of anxiolytic effect elevated plus maze, social interaction and Vogel tests were provided as well as examination of locomotor activity. Results: The dry extract of Satureja montana at both tested doses significantly increased locomotor activity as well as the time spent in the social recognition, compared to the control groups. The extract reduced the time in the closed arms and the proportion of entries into open arms to total entries and increased the time in the open arms of elevated plus maze compared to the positive control group. Likewise, rosmarinic acid and carvacrol increased significantly the time spent with a new congener in the social interaction test. Both compounds reduced the ratio of entries into open arms to total entries similarly to the dry extract of Satureja montana. Only rosmarinic acid increased the time in the open arms and reduced the time in the closed arms. Conclusions: Satureja montana at both experimental doses exerted a significant anxiolytic activity in almost all the tests employed for evaluating anxious behavior. Carvacrol and rosmarinic acid showed a moderate anxiolytic effect.

The main symptoms of schizophrenia are categorized as positive, negative, and cognitive. Cognitive impairments do not generally respond to antipsychotics. Cariprazine is a novel antipsychotic conceived with the idea that high affinity for D3 receptors may elicit a favorable response in the management of cognitive deficits. We evaluated the pro-cognitive properties of 14-day long pre-treatment with cariprazine (0.25, 0.5, and 1 mg/kg b.w. intraperitoneally) in experimental rodent models with scopolamine-induced memory impairment employing novel object recognition test (NORT), T-maze, Y-maze, and passive avoidance tasks (step-through and step-down). Statistical analysis was performed with One Way ANOVA. In NORT cariprazine increased the recognition index. In T-maze and Y-maze cariprazine increased the working memory index as well as the percentage of spontaneous alternation. Cariprazine improved learning and memory in both short-term and long-term memory retention tests in step-down and step-through tasks. Cariprazine improves learning, recognition, and spatial memory in rats with scopolamine-induced memory impairment. Cariprazine’s beneficial effect on cognition is likely due to its affinity for D3 receptors, as well as agonism at 5-HT1A receptors. Most probably, the cognitive-enhancing properties of cariprazine are the result of integrated modulation in the amygdala, hippocampus, and prefrontal cortex.

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, is believed to have anxiety-reducing and antidepressant effects. However, existing data are inconsistent, likely due to variations in experimental designs, dosages, and stress models. This study sought to assess the impact of CBD on anxiety and depression-like behaviors in Wistar rats exposed to acute cold stress, as well as its impact on pro- and anti-inflammatory cytokines. Male rats were treated with CBD (2.5, 5, or 10 mg/kg) or vehicle for 14 days and subjected to behavioral tests, including the elevated plus maze, social interaction, and forced swim tests. Serum levels of cytokines (IL-6, TNF-α, IL-1β, and IL-10) were analyzed post-experiment using ELISA. Results demonstrated a dose-dependent anxiolytic effect of CBD, with significant improvements in social interaction and reductions in anxiety-like behaviors at 5 and 10 mg/kg. All doses of CBD decreased immobility in the forced swim test, suggesting antidepressant effects. Furthermore, CBD selectively lowered IL-6 levels, a key cytokine in acute stress and depression pathogenesis. These findings indicate that CBD has anxiety-reducing and antidepressant properties, partially mediated by modulation of inflammatory processes, particularly IL-6.

Aim: Memory improving and anti-inflammatory properties of cannabidiol (CBD) were investigated in an experimental model of lipopolysaccharide (LPS)-induced inflammation. Materials and methods: Male Wistar rats were randomly divided into 4 groups: control, LPS control, LPS + CBD 5 mg/kg bw, and LPS + CBD 10 mg/kg bw. Animals were treated with CBD 14 days before LPS administration and throughout the experiment. Step-through passive avoidance task, Y-maze, and novel object recognition test (NORT) were used to assess the memory functions. The following parameters were recorded: latency time, spontaneous alternations percentage (SA%) and recognition index (RI). IL-10, IL-6, TNF-α, and IL-1β serum levels were measured to evaluate the immunomodulatory properties of CBD. Results: LPS led to significant decrease of the recorded parameters in all memory tasks. This demonstrated the memory-impairing effect of LPS-induced inflammation. In the Y-maze and NORT tests, both doses of CBD increased SA% and RI, respectively. Significant difference was found in comparison with the LPS controls. Rats from the CBD treated groups showed increased latency in the step-through passive avoidance task. In the short-term memory test, both CBD doses significantly increased this parameter when compared with both control groups (p<0.05 and p<0.001, respectively), whereas in the long-term memory test, statistical significance was reached only in comparison with the LPS controls (p<0.01). CBD treatment failed to reduce TNF-α and IL-6 serum levels. The lower studied dose significantly decreased IL-10 and IL-1β concentrations compared to LPS controls (p<0.01 and p<0.05, respectively). Conclusions: CBD improved spatial working and recognition memory in rats with LPS-induced inflammation. Suppression of IL-1β production could be attributed to the observed effect.

Introduction: Satureja montana is a wild growing medicinal plant, part of the Lamiaceae family. This herb is well known as a source of phenolic compounds, which can vary in a broad range depending on different factors and exert many pharmacological activities. Aim: The aim of the study was to investigate the composition and chronic toxicity of dry extract of Satureja montana. Material and methods: The composition was investigated by high-performance liquid chromatographic system with diode-array detector. To establish the chronic toxicity of dry extract of Satureja montana we used 40 eight-week-old male Wistar rats, treated orally with saline, olive oil (control groups), Satureja montana at a dose of 500 mg/kg bw, carvacrol – 500 mg/kg bw, and rosmarinic acid – 15 mg/kg bw. The animals were sacrificed at the end of the experiment and blood samples and organs for histological examination were obtained. Statistical analysis was performed with one-way analysis of variance (ANOVA) using IBM SPSS 19.0. Results: Rosmarinic acid and small quantities of carvacrol were found in the dry extract of Satureja montana. Full blood count and the biochemical parameters ASAT, ALAT, uric acid, cholesterol, triglycerides, glucose and ionized Ca were in the reference values for 17+ weeks old male Wistar rats. The histological samples showed no signs of organ toxicity. Conclusions: The main ingredient in the dry extract of Satureja montana is rosmarinic acid. The extract is not toxic after 90-days oral administration.