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The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline, coenzyme Q10 (CoQ10) and a fixed combination of them in countering the oxidative stress and neurotoxicity occurring in neurological diseases. Rat CTX-TNA2 astrocytes, which have considerable antioxidant potential and could represent a key target for neurotherapies were selected as in vitromodel to conduct the experiments. The efficacy of citicoline and coenzyme Q10 (1 nM-10 μM), with their fixed combination, were assayed in rat astrocytes either in basal condition or after challenging the cells with hydrogen peroxide in order to evaluate the biocompatibility of treatments. The gene expression of B-Cell Lymphoma protein 2 (BCL-2), BCL-2 Associated X (BAX), Superoxide dismutase 2 (SOD2), Cardiolipin Synthase 1 (CRLS1), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) involved in neurodegenerative diseases and neuroinflammation were investigated in CTX-TNA2 cells. Furthermore, in the same condition, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was carried out to assess apoptosis in astrocytes. Neither citicoline, nor coenzyme Q10 significantly altered astrocytes cell viability; thus, suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. Moreover, each compound tested alone or in combination were effective in inhibiting the hydrogen peroxide-induced gene expression of BAX, and SOD2, in inducing the gene expression of BCL-2 and CRLS1 and in reducing apoptosis. The blunting effects induced by the abovementioned treatments on hydrogen-peroxide induced apoptosis was also confirmed by TUNEL assay that demonstrated the capability of citicoline, CoQ10, and their combination to reduce the ratio TUNEL positive nuclei/total nuclei, a reliable marker of apoptosis. Additionally, citicoline, CoQ10, and their association were effective in inhibiting the hydrogen peroxide-induced NFkB, TNFα, and IL-6 gene. In parallel, there was an inhibition of both TNFα and IL-6 gene expression in basal condition. The co-administration of citicoline/coenzyme Q10 was overall more effective than individual ingredients. The present findings support the beneficial and synergistic effects of citicoline and coenzyme Q10 in fixed combination in reducing oxidation, and in stimulating neuroprotection in rat CTX-TNA2 astrocytes.

The study focused on investigating the phytochemical composition and bio-pharmacological properties of a water extract obtained from industrial hemp by-products, after trimming female inflorescences of Cannabis sativaL., cultivar Kompolti. The extract was found to be rich in phenolic compounds, particularly gallic acid, catechin, coumaric acid, ferulic acid, and benzoic acid. It also contained significant amounts of cannabidiolic acid and cannabigerolic acid as the main terpenophenols. To assess the biological potential of the extract, various ecotoxicological assays were conducted. The extract did not show significant phytotoxic effects on seedling germination in the allelopathic assay. In the brine shrimp (Artemia salina) lethality test, the LC50value was 1.726 mg/mL, and in the Daphnia magnatest, the extract showed no cardiotoxicity effects at the same concentration; thus, confirming its biocompatibility with these eukaryotic organisms. Additionally, the extract did not induce cytotoxicity in the murine C2C12 cell line till to the concentration of 1000 μg/mL. In isolated mouse prostate specimens, the extract (10–1000 μg/mL) also prevented LPS-induced gene expression of pro-inflammatory cytokines, namely tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-1β. Furthermore, the extract exhibited inhibitory effects on the growth of pathogenic bacterial, fungal, and dermatophyte species commonly associated with prostatitis. These results suggest that the residual powder from female inflorescence trimming can be considered an innovative plant material from the industrial hemp supply chain that deserves to be valorised in terms of recycling and upcycling; thus, reducing the environmental impact of the by-products and also opening the way for innovative health-promoting agents.

Anxiety and depression have been suggested to increase the risk for post-traumatic stress disorders (PTSD). A link between all these mental illnesses, inflammation and oxidative stress is also well established. Recent behavior studies by our group clearly demonstrate a powerful anxiolytic and antidepressant-like effects of a novel growth hormone releasing hormone (GHRH) antagonist of MIAMI class, MIA-690, probably related to modulatory effects on the inflammatory and oxidative status. In the present work we investigated the potential beneficial effects of MIA-602, another recently developed GHRH antagonist, in mood disorders, as anxiety and depression, and the possible brain pathways involved in its protective activity, in adult mice. MIA-602 exhibited antinflammatory and antioxidant effects in ex vivo and in vivo experimental models, inducing anxiolytic and antidepressant-like behavior in mice subcutaneously treated for 4 weeks. The beneficial effect of MIA-602 on inflammatory and oxidative status and synaptogenesis resulting in anxiolytic and antidepressant-like effects could be related by increases of nuclear factor erythroid 2-related factor 2 (Nrf2) and of brain-derived neurotrophic factor (BDNF) signaling pathways in the hippocampus and prefrontal cortex. These results strongly suggest that GHRH analogs should be tried clinically for the treatment of mood disorders including PTSD.

•Central RVD-Hemopressin(α) injection reduced norepinephrine level.•Central RVD-Hemopressin(α) injection reduced orexin-A gene expression.•Central RVD-Hemopressin(α) injection reduced POMC gene expression.

Growth hormone-releasing hormone (GHRH) plays an important role in brain functions. The aim of this study was to examine cognitive functions and emotional behaviour in a mouse model of isolated GH deficiency due to bi-allelic ablation of the GHRH gene (GHRH knockout, GHRHKO).Learning, memory and emotional behaviour were evaluated using a series of validated tests (Morris water maze, eight-arm radial maze, open field, elevated plus maze test, forced swim tests) in 2-, 5- and 12-month-old male mice either homozygous (−/−) or heterozygous (+/−) for the GHRHKO allele.Compared with age-matched +/− mice, −/− mice showed decreased cognitive performance in Morris water maze and eight-arm radial maze tests. By comparing the effects of aging in each genotype, we observed an age-related impairment in test results in +/− mice, while in −/− mice a significant decline in cognitive function was found only in 12 months compared with 2-month-old mice, but no difference was found between 5 months old vs 2 months old. −/− mice showed increased exploration activity compared to age-matched +/− controls, while both strains of mice had an age-related decrease in exploration activity. When evaluated through open field, elevated plus maze and forced swim tests, −/− mice demonstrated a decrease in anxiety and depression-related behaviour compared to age-matched +/− controls.Our results suggest that homozygous ablation of GHRH gene is associated with decreased performance in learning and memory tests, possibly linked to increased spontaneous locomotor activity. In addition, we observed an age-related decline in cognitive functions in both genotypes.

•RVD-Hemopressin(α) decreased anxiety and depression.•Hemopressin increased anxiety and depression.•RVD-Hemopressin(α) increased monoamine activity.•Hemopressin decreased monoamine activity.•RVD-Hemopressin(α) and Hemopressin modulate MAO-B and COMT gene expression.

•RVD-Hemopressin(α) decreased food intake.•RVD-Hemopressin(α) decreased hypothalamic NE level.•RVD-Hemopressin(α) decreased hypothalamic POMC gene expression.•RVD-Hemopressin(α) decreased BAT UCP-1 gene expression.

Omentin is an adipokine expressed in visceral adipose tissue (VAT). In vitrostudies demonstrated that omentin induces vasorelaxation in isolated rat mesenteric arteries, and in vivostudies showed inhibition of agonist-induced increases in blood pressure, possibly mediated by nitric oxide (NO)-dependent mechanisms.

A detailed comprehension of central mechanisms underlying feeding behavior holds considerable promise for the treatment of alimentary disorders

Isoprostanes are prostaglandin (PG) isomers generated from oxygen radical peroxidation of arachidonic acid, which are reliable markers of membrane oxidative damage. Aging is characterized by an imbalance between the generation of reactive oxygen species and antioxidant detoxification pathways. GINKGO BILOBA leaf extract is reputed as a neuroprotective antioxidant agent. We have tested the effects of a GINKGO BILOBA extract {containing 24.1 % flavonoids and 181 % terpene lactones [bilobalide (0.542 %), ginkgolide A (0.570 %), ginkgolide B (0.293 %), ginkgolide C (0.263 %), and ginkgolide J (0.138 %)]} on the production of 8-iso-PGF 2? from rat brain synaptosomes obtained from young (3 months old) or aged (12 and 24 months old) rats, both in the basal state and after oxidative stress induced by either hydrogen peroxide or amyloid ?-peptide. Our findings show that GINKGO BILOBA extract pretreatment is able to completely reverse both basal and hydrogen peroxide-stimulated isoprostane production (IC 50 of 81.92 ?M and 31.89 ?M, respectively). Amyloid ?-peptide-induced isoprostane production was also inhibited, both in young and aged rats, to a level even lower than that in unstimulated synaptosomes. This suggests that the oxygen radical scavenging properties of the GINKGO BILOBA extract are fully effective in young, as well as in old rats, showing a greater inhibition of isoprostane production in the latter.