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.

Echinacea purpurea and Onopordum acanthium, which belong to the Asteraceae family, are widely used plants in traditional medicine. Their antioxidant, anti-inflammatory, antiviral, antibacterial, and antitumor effects are well known. However, there are no data on the effects of their combination. The aim of the present study was to combine E. purpurea with O. acanthium to study the in vivo immunomodulatory effect of two combinations and to compare it with that of single plants. Their total polyphenolic and flavonoid content and the amounts of individual compounds characteristic of both species were determined. The influence of the obtained extracts on the serum concentrations of cytokines IFN-γ, TNF-α, and IL-10 in experimental animals with lipopolysaccharide-induced systemic inflammatory response was investigated. This research found that a combination of E. purpurea/O. acanthium in the ratio 1:1 reduced the proinflammatory cytokines TNF-α (244.82 pg/mL) and IFN-γ (1327.92 pg/mL) compared to the LPS-control, respectively, (574.17 pg/mL) and (3354.00 pg/mL), and the combination E. purpurea/O. acanthium in the ratio of 3:1 significantly increased the levels of the anti-inflammatory cytokine IL-10 (1313.95 pg/mL) compared to the LPS-control (760.09 pg/mL). In conclusion, our results could be a basis for future biomedical research on creating phytopreparations with an immunomodulatory effect.

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.

Recently, compounds of plant origin have been the focus of increased scientific interest. Micromeria frivaldszkyana is a rare species endemic to Bulgaria, whose biological activity remains unknown. This article aims to evaluate the subchronic toxicity of Micromeria frivaldszkyana methanolic extract and its effect on cognition in rats. Following 90 days of oral administration, a histopathological evaluation of brain, kidney, and liver tissues was conducted. Additionally, serum levels of total bilirubin (TB), conjugated bilirubin (CB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR), uric acid (UA), and urea (U) were measured. Cognitive function was studied after 7 d of treatment using activity cage test, along with tests for active memory, passive memory, anxiety, spatial and working memory, and explorative activity. The experiments showed no toxic effects of the extract in subchronic application. No adverse effects on brain function were observed after 14 days of treatment. While the extract increased the motor activity of the animals, it did not significantly improve the learning and memory processes. In conclusion, the methanolic extract of Micromeria frivaldszkyana in doses 250 and 500 mg/kg bw did not induce toxicity after 90-day treatment in rats. These doses did not significantly affect central nervous system (CNS) functions, although increased motor activity was observed after 14 days of treatment with the extract.

Nigella sativa (NS) is a promising medicinal plant with diverse therapeutic properties. This study aimed to investigate the impact of NS oil (NSO) on memory functions in rats with LPS (lipopolysaccharide)-induced neuroinflammation, as well as its effect on serum levels of inflammatory cytokines, neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF). Male rats were divided into four groups: control, LPS-control, LPS+NSO 3 and 5 mL/kg. Neuroinflammation was induced by a single intraperitoneal LPS injection (2 mg/kg). The novel object recognition test (NORT) and Y-maze were used for the evaluation of memory processes. Recognition index (RI) and % spontaneous alteration (%SA) were registered, respectively. Blood samples for TNF-α, IL-1β, IL-10, BDNF, and NPY serum levels were taken. Thymoquinone, the active compound of the oil, was detected by high-performance liquid chromatography. NSO administration resulted in an improvement in spatial and episodic memory, as evidenced by increased % SA and RI compared to LPS-control. Treatment with NSO led to a significant reduction in pro-inflammatory cytokines and NPY, along with an increase in IL-10 and BDNF levels, when compared to LPS-control. In conclusion, NSO enhances BDNF production and regulates pro- and anti-inflammatory cytokines release, which probably contributes to the observed cognitive improvement in animals with experimental neuroinflammation.

Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg/kg rosmarinic acid (RA); or 125 mg/kg silymarin. Liver toxicity was induced by oral application of 2000 mg/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA).