Pelargonium quercetorum is a medicinal plant traditionally used for treating intestinal worms. In the present study, the chemical composition and bio-pharmacological properties of P. quercetorum extracts were investigated. Enzyme inhibition and scavenging/reducing properties of water, methanol, and ethyl acetate extracts were assayed. The extracts were also studied in an ex vivo experimental model of colon inflammation, and in this context the gene expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) were assayed. Additionally, in colon cancer HCT116 cells, the gene expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), possibly involved in colon carcinogenesis, was conducted as well. The extracts showed a different qualitative and quantitative content of phytochemicals, with water and methanol extracts being richer in total phenols and flavonoids, among which are flavonol glycosides and hydroxycinnamic acids. This could explain, at least in part, the higher antioxidant effects shown by methanol and water extracts, compared with ethyl acetate extract. By contrast, the ethyl acetate was more effective as cytotoxic agent against colon cancer cells, and this could be related, albeit partially, to the content of thymol and to its putative ability to downregulate TRPM8 gene expression. Additionally, the ethyl acetate extract was effective in inhibiting the gene expression of COX-2 and TNFα in isolated colon tissue exposed to LPS. Overall, the present results support future studies for investigating protective effects against gut inflammatory diseases.

Vitis vinifera (grape) contains various compounds with acknowledged phytochemical and pharmacological properties. Among the different parts of the plant, pomace is of particular interest as a winemaking industry by-product. A characterization of the water extract from grape pomace from Montepulciano d'Abruzzo variety (Villamagna doc) was conducted, and the bioactive phenolic compounds were quantified through HPLC-DAD-MS analysis. HypoE22, a hypothalamic cell line, was challenged with an oxidative stimulus and exposed to different concentrations (1 µg/mL-1 mg/mL) of the pomace extract for 24, 48, and 72 h. In the same conditions, cells were exposed to the sole catechin, in a concentration range (5-500 ng/mL) consistent with the catechin level in the extract. Cell proliferation was investigated by MTT assay, dopamine release through HPLC-EC method, PGE2 amount by an ELISA kit, and expressions of neurotrophin brain-derived neurotrophic factor (BDNF) and of cyclooxygenase-2 (COX-2) by RT-PCR. The extract reverted the cytotoxicity exerted by the oxidative stimulus at all the experimental times in a dose-dependent manner, whereas the catechin was able to revert the oxidative stress-induced depletion of dopamine 48 h and 72 h after the stimulus. The extract and the catechin were also effective in preventing the downregulation of BDNF and the concomitant upregulation of COX-2 gene expression. In accordance, PGE2 release was augmented by the oxidative stress conditions and reverted by the administration of the water extract from grace pomace and catechin, which were equally effective. These results suggest that the neuroprotection induced by the extract could be ascribed, albeit partially, to its catechin content.

Peptide YY (1-36) and peptide YY (3-36) are gut-derived hormones which are involved in feeding control in the hypothalamus. The hypothalamic mechanisms of feeding have been shown to be modulated by aminergic neurotransmitters, which could mediate the anorectic or orexigenic effects of neuropeptides and hormones. We have investigated the role of peptide YY (1-36) and peptide YY (3-36) on dopamine, norepinephrine, and serotonin release from hypothalamic synaptosomes in vitro. We found that peptide YY (3-36) inhibited depolarization-induced dopamine and norepinephrine release, leaving unaffected serotonin release, while peptide YY (1-36) did not modify either basal or stimulated amine release. We can hypothesize that the effects of peptide YY (3-36) could be mediated by inhibited hypothalamic dopamine and norepinephrine release, which could partially account for the anorectic activity of the peptide. On the other hand, peptide YY (1-36), which has a feeding stimulatory role, does not affect aminergic neurotransmission in the hypothalamus.

The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress.

Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. is a well-known African medicinal plant traditionally used for various healing purposes. In the present study, methanolic, ethyl acetate and infusion extracts of A. cordifolia leaves were studied for their total phenolic and flavonoid contents and screened for their chemical composition. Moreover, the enzyme (acetyl- and butyryl-cholinesterases, α-amylase, α-glucosidase, and tyrosinase) inhibitory and cytotoxicity activities on HepG2: human hepatocellular carcinoma cells, B16 4A5: murine melanoma cells, and S17: murine bone marrow (normal) cells of extracts were evaluated. Finally, components-targets and docking analyzes were conducted with the aim to unravel the putative mechanisms underlying the observed bio-pharmacological effects. Interestingly, the infusion and methanolic extracts showed significantly higher total phenolic and flavonoid contents compared with the ethyl acetate extract (TPC: 120.38-213.12 mg GAE/g and TFC: 9.66-57.18 mg RE/g). Besides, the methanolic extracts followed by the infusion extracts were revealed to contain a higher number of compounds (84 and 74 compounds, respectively), while only 64 compounds were observed for the ethyl acetate extract. Gallic acid, ellagic acid, shikimic acid, rutin, quercetin, myricetin, vitexin, quercitrin, kaempferol, and naringenin were among the compounds that were commonly identified in all the studied extracts. Additionally, the methanolic and infusion extracts displayed higher antioxidant capacity than ethyl acetate extract in all assays performed. In ABTS and DPPH radical scavenging assays, the methanol extract (500.38 mg TE/g for DPPH and 900.64 mg TE/g for ABTS) exhibited the best ability, followed by the water and ethyl acetate extracts. Furthermore, the extracts exhibited differential enzyme inhibitory profiles. In particular, the methanolic and infusion extracts showed better cytotoxic selectivity activity against human hepatocellular carcinoma cells. Overall, this study demonstrated A cordifolia to be a species worthy of further investigations, given its richness in bioactive phytochemicals and wide potentialities for antioxidants and pharmacological agents.

Parkinson's disease (PD) is the most common and progressive neurodegenerative and oxidative stress-related disorder, characterized by a dramatic loss of dopamine (DA) neurons in the nigrostriatal tissue. The first-line drug for PD treatment is represented by l-dopa, although clinical and preclinical studies pointed out the potential efficacy of medicinal plant- and food-derived antioxidants as brain protective agents. In this regard, the potential application of Vicia faba, Uncaria rhyncophylla, and Glycyrrhiza glabra extracts is of noteworthy interest, despite a lack of information in the scientific literature as regards their effect on striatal DA level.

Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

MOMAST(®) HY100 and MOMAST(®) HP30 are polyphenolic liquid complexes from olive pressing juice with a total polyphenolic content of 100 g/kg (at least 50% as hydroxytyrosol) and 36 g/kg (at least 30% as hydroxytyrosol), respectively. We investigated the potential protective role of MOMAST(®) HY100 and MOMAST(®) HP30 on isolated rat colon, liver, heart, and prefrontal cortex specimens treated with Escherichia coli lipopolysaccharide (LPS), a validated ex vivo model of inflammation, by measuring the production of prostaglandin (PG)E2, 8-iso-PGF2α, lactate dehydrogenase (LDH), as well as cyclooxygenase (COX)-2, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA levels. MOMAST(®) HY100 decreased LPS-stimulated PGE2 and LDH levels in all tested tissues. Following treatment with MOMAST(®) HY100, we found a significant reduction in iNOS levels in prefrontal cortex and heart specimens, COX-2 and TNFα mRNA levels in heart specimens, and 8-iso-PGF2α levels in liver specimens. On the other hand, MOMAST(®) HP30 was found to blunt COX-2, TNFα, and iNOS mRNA levels, as well as 8-iso-PGF2α in cortex, liver, and colon specimens. MOMAST(®) HP30 was also found to decrease PGE2 levels in liver specimens, while it decreased iNOS mRNA, LDH, and 8-iso-PGF2α levels in heart specimens. Both MOMAST(®) HY100 and MOMAST(®) HP30 exhibited protective effects on multiple inflammatory and oxidative stress pathways.

Titanium implant surfaces are continuously modified to improve biocompatibility and to promote osteointegration. Graphene oxide (GO) has been successfully used to ameliorate biomaterial performances, in terms of implant integration with host tissue. The aim of this study is to evaluate the Dental Pulp Stem Cells (DPSCs) viability, cytotoxic response, and osteogenic differentiation capability in the presence of GO-coated titanium surfaces.

Prostatitis, a general term describing prostate inflammation, is a common disease that could be sustained by bacterial or non-bacterial infectious agents. The efficacy of herbal extracts with antioxidant and anti-inflammatory effects for blunting the burden of inflammation and oxidative stress, with possible improvements in clinical symptoms, is under investigation. Pollen extracts have been previously reported as promising agents in managing clinical symptoms related to prostatitis. The aim of the present work was to evaluate the protective effects of Graminex pollen (GraminexTM, Deshler, OH, USA), a commercially available product based on standardized pollen extracts, in rat prostate specimens, ex vivo. In this context, we studied the putative mechanism of action of pollen on multiple inflammatory pathways, including the reduction of prostaglandin E₂ (PGE₂), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and malondialdehyde (MDA), whose activities were significantly increased by inflammatory stimuli. We characterized by means of chromatographic and colorimetric studies the composition of Graminex pollen to better correlate the activity of pollen on immortalized prostate cells (PC3), and in rat prostate specimens challenged with Escherichia coli lipopolysaccharide (LPS). We found that Graminex pollen was able to reduce radical oxygen species (ROS) production by PC3 cells and MDA, NFκB mRNA, and PGE₂ levels, in rat prostate specimens. According to our experimental evidence, Graminex pollen appears to be a promising natural product for the management of the inflammatory components in the prostate.

Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed.

Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses.

MOMAST® GR25 is a polyphenolic granular complex from olive pressing juice with high total content in polyphenols. In this work, we evaluated the possible anti-inflammatory effects of MOMAST® GR25 in both acute and chronic inflammatory models. MOMAST® GR25 decreased the levels of prostaglandin (PG) E2 and 8-iso-PGF2α in isolated rat colon, liver, and heart specimens stimulated with lipopolysaccharide (LPS). In vivo, compared to controls, rats treated with MOMAST® GR25 (100 mg/kg to 1 g/kg) showed a significant reduction in both licking/biting time in the formalin test. In a rat model of osteoarthritis by monoiodoacetate (MIA) injection, MOMAST® GR25 showed pain-relieving properties when acutely administered, reducing mechanical hyperalgesia and spontaneous pain. Moreover, a repeated daily treatment with MOMAST® GR25 (300 mg/kg) fully counteracted osteoarticular pain without the development of tolerance to the antinociceptive effect. Taken together, our present findings showed that MOMAST® GR25 could represent a potential strategy for the treatment of inflammation and pain.

Inflammatory bowel diseases (IBDs) are chronic and multifactorial inflammatory conditions of the colonic mucosa (ulcerative colitis), characterized by increased and unbalanced immune response to external stimuli. Garlic and its bioactive constituents were reported to exert various biological effects, including anti-inflammatory, antioxidant and immunomodulatory activities. We aimed to evaluate the protective effects of a hydroalcoholic (GHE) and a water (GWE) extract from a Sicilian variety of garlic, known as Nubia red garlic, on an ex vivo experimental model of ulcerative colitis, involving isolated LPS-treated mouse colon specimens. Both extracts were able to counteract LPS-induced cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, nuclear factor-kB (NF-kB), and interleukin (IL)-6 gene expression in mouse colon. Moreover, the same extracts inhibited prostaglandin (PG)E2, 8-iso-PGF2α, and increased the 5-hydroxyindoleacetic acid/serotonin ratio following treatment with LPS. In particular, GHE showed a better anti-inflammatory profile. The anti-inflammatory and antioxidant effects induced by both extracts could be related, at least partially, to their polyphenolic composition, with particular regards to catechin. Concluding, our results showed that GHE and GWE exhibited protective effects in colon, thus suggesting their potential use in the prevention and management of ulcerative colitis.

Growth hormone (GH)-releasing hormone (GHRH) has been suggested to play a crucial role in brain function. We aimed to further investigate the effects of a novel GHRH antagonist of the Miami (MIA) series, MIA-602, on emotional disorders and explore the relationships between the endocrine system and mood disorders. In this context, the effects induced by MIA-602 were also analyzed in comparison to vehicle-treated mice with GH deficiency due to generalized ablation of the GHRH gene (GHRH knock out (GHRHKO)). We show that the chronic subcutaneous administration of MIA-602 to wild type (+/+) mice, as well as generalized ablation of the GHRH gene, is associated with anxiolytic and antidepressant behavior. Moreover, immunohistochemical and Western blot analyses suggested an evident activation of Nrf2, HO1, and NQO1 in the prefrontal cortex of both +/+ mice treated with MIA-602 (+/+ MIA-602) and homozygous GHRHKO (-/- control) animals. Finally, we also found significantly decreased COX-2, iNOS, NFkB, and TNF-α gene expressions, as well as increased P-AKT and AKT levels in +/+ MIA-602 and -/- control animals compared to +/+ mice treated with vehicle (+/+ control). We hypothesize that the generalized ablation of the GHRH gene leads to a dysregulation of neural pathways, which is mimicked by GHRH antagonist treatment.