Introduction: The Ginkgo biloba L. tree is considered as one of the oldest species on Earth. It is known as a “living fossil” dating back approximately 200 million years. Both the leaves and seeds of this tree have been used for millennia in traditional Chinese medicine. Aim: To study the phytochemical profile of Gingko biloba seed extract (GBSE) and its memory enhancing effects. Materials and methods: Liquid chromatography with mass detection (LC-MS) was performed for phytochemical analyses of the extracts. For the in vivo experiments, male Wistar rats were divided randomly into 5 groups (n=8): saline; piracetam; GBSE 50; 100, and 200 mg/kg b.w. Y-maze, T-maze, step-down passive avoidance and novel object recognition test (NORT) were performed. The observed parameters were: percentage of spontaneous alternations (% SA), working memory index, latency of reaction and recognition index, respectively. Statistical analysis was done using SPSS 19. Results: LC-MS analysis showed the presence of the flavonoids quercetin, kaempferol and isorhamnetin (as aglycones), the ginkgolides A, B, C, J, and bilobalide. In Y-maze task, the groups treated with 50 and 100 mg/kg of GBSE significantly increased the % SA during the memory test compared to saline (p<0.05). In T-maze test, the three experimental groups with GBSE significantly increased the working memory index in comparison with that of the control group (p<0.05). In step-down test, the animals receiving 100 mg/kg b.w. GBSE, notably increased the latency during both retention tests (p<0.05 and p<0.01, respectively). In NORT, only the animals with the middle dose of GBSE ameliorated the recognition index when compared to saline (p<0.05). Conclusions: GBSE enhances spatial working memory, recognition memory, and short- and long-term recall in naïve rats due to the synergic effects of detected flavonoids and terpene lactones on brain functions. The brain structures involved are probably the hippocampus and prefrontal cortex.

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.

Objective(s): Dopamine plays an important role in cognitive functions. Inhibition of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT) may have beneficial effects. Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naive and haloperidol-challenged rats. Materials and Methods: Male Wistar rats were divided into 9 groups (n=8): naive-saline, tolcapone 5; 15 and 30 mg/kg BW; haloperidol (HP) challenged-saline, haloperidol, haloperidol+tolcapone 5; 15 and 30 mg/kg BW. Two-way active avoidance test (TWAA), elevated T-maze, and activity cage were performed. Observed parameters were: number of conditioned responses (CR) and unconditioned responses (UCR), working memory index, and vertical and horizontal movements. Results: Naive rats with 30 mg/kg BW TCP had a significantly increased number of CR and UCR during the long-term memory test. The animals with 5 mg/kg BW TCP significantly increased the number of UCR during the two retention tests. In haloperidol-challenged rats, the three experimental groups decreased the number of CR and UCR during the learning session and the two memory tests, compared to the saline group. There was no significant difference between the HP-challenged rats treated with TCP and the haloperidol control group. All experimental naive groups had significantly increased working memory index whereas none of the HP-challenged groups showed significant increase in this parameter. Conclusion: Our results demonstrate that in naive rats tolcapone improves memory in the hippocampal-dependent TWAA task and spatial working memory in T-maze.

Objective(s): A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF) levels in lipopolysaccharide (LPS) challenged-rats. Materials and Methods: Male Wistar rats were divided into 5 groups (n=8): control (saline), lipoppolysacharide (LPS 250 mcg/kg bw), and experimental groups (LPS and PMX 0.5, 1, and 3 mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed. Results: In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX 1 mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of 0.5 and 1 mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-10 serum levels were elevated by 1 mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration.Conclusion: In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-10.

Weightlessness significantly impacts physiological systems. In the current study, we investigate the effects of 7 days exposure of rats to simulated microgravity (using a modified rat-modeled random positioning machine, working with four experimental animals simultaneously) on local carrageenan-induced inflammation and serum levels of liver enzymes, metabolites (glucose, urea, creatinine), and metabolic hormones (thyroid-stimulating hormone – TSH, aldosterone, cortisol). Male Wistar rats (n=12, m=200 ± 20 g) were evenly divided into RPM (experimental) and RPM-K (control) groups. The RPM rats showed a notable mass decrease compared to the controls. A significant increase in the carrageenan-induced inflammatory response was reached on the 24^th hour in the RPM group compared to the RPM-K. Simulated microgravity resulted in lower serum glucose, creatinine, cortisol, and elevated urea levels. In conclusion, 7 days of exposure to random positioning machine-simulated microgravity promotes a pro-inflammatory state, potentially affecting insulin sensitivity, glucose utilization, and muscle catabolism.

The study aimed to investigate anti-inflammatory and immunomodulatory effects of cholecalciferol (vitamin D₃) in rats with complete Freund’s adjuvant-induced arthritis (AIA) and lipopolysaccharide (LPS)-induced inflammation. In the first experiment, rats were treated with cholecalciferol 14 days before or from the day of induction of arthritis. In the second set-up, animals received cholecalciferol for 14 days which was followed by LPS injection. TNF (tumour necrosis factor)-alpha, IL (interleukin)-1β, TGF (transforming growth factor)-β1 levels were measured by enzyme linked immunosorbent assay (ELISA). Cholecalciferol treatment reduced paw oedema and ankle joint diameter in AIA. Significantly lower IL-1β concentrations were found in cholecalciferol-treated arthritic rats. In LPS-challenged rats, cholecalciferol markedly lowered serum TNF-α, whereas an elevation in IL-1β concentrations was observed. Cholecalciferol slightly increased TGF-β1 serum concentration in arthritic rats and non-significantly reduced its level in LPS-challenged animals. Our findings showed that cholecalciferol exerts immunomodulatory properties which probably contribute to its anti-inflammatory effect.