Beneficial Effects Induced by a Proprietary Blend of a New Bromelain-Based Polyenzymatic Complex Plus N-Acetylcysteine in Urinary Tract Infections: Results from In Vitro and Ex Vivo Studies.

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies.

Investigation of the chemical composition and biological activities of Eremurus spectabilis M. Bieb through antioxidant, enzyme inhibition, COX-2 and iNOS assessment.

Eremurus spectabilis is widespread and used primarily for medicinal and culinary purposes. This study aimed to evaluate the chemical composition, antiradical and antioxidant activities, enzyme inhibitory activities, and anti-inflammatory properties of various extracts from the aerial parts of E. spectabilis. Various assays were used to investigate the antioxidant and enzyme inhibitory properties. The chemical composition of the tested extracts was analyzed using High-Performance Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MS/MS). Additionally, the extracts were tested on isolated mouse colon tissue challenged with E. coli lipopolysaccharide (LPS) to replicate the inflammation and oxidative stress burden characteristic of inflammatory bowel diseases. In the chemical composition, vanillic, ferulic,  4-hydroxybenzoic acids were the prominent compounds. The greatest antioxidant activity was observed in the methanol and water extracts from the aerial parts. Enzyme inhibition tests showed that the ethyl acetate extract had the highest anti-acetylcholinesterase activity. The gene expression of pro-inflammatory cyclooxygenase-2 (COX-2) and pro-oxidant inducible nitric oxide synthase (iNOS) biomarkers were assayed. Among the extracts, the methanol extract was the most effective in blunting LPS-induced gene expression of COX-2. E. spectabilis may serve as a valuable source of phytochemicals for combating oxidative stress and inflammation-driven diseases, with a particular emphasis on colon inflammatory condition.

The Protective Effects of an Aged Black Garlic Water Extract on the Prostate.

Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE's therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-ß). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer.

Anti-inflammatory and anti-hyperalgesic effects induced by an aqueous aged black garlic extract in rodent models of ulcerative colitis and colitis-associated visceral pain.

Inflammatory bowel disease (IBD) is a morbid condition characterized by relapsing-remitting inflammation of the colon, accompanied by persistent gut dysmotility and abdominal pain. Different reports demonstrated biological activities of aged black garlic (ABG), including anti-inflammatory and antioxidant effects. We aimed to investigate beneficial effects exerted by ABGE on colon inflammation by using ex vivo and in vivo experimental models. We investigated the anti-inflammatory effects of an ABG water extract (ABGE) on rat colon specimens exposed to E. coli lipopolysaccharide (LPS), a known ex vivo experimental model of ulcerative colitis. We determined gene expression of various biomarkers involved in inflammation, including interleukin (IL)-1ß, IL-6, nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α. Moreover, we studied the acute effects of ABGE on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) injection in rats. ABGE suppressed LPS-induced gene expression of IL-1ß, IL-6, NF-kB, and TNF-α. In addition, the acute administration of ABGE (0.03-1 g kg-1) dose-dependently relieved post-inflammatory visceral pain, with the higher dose (1 g kg-1) able to significantly reduce both the behavioral nociceptive response and the entity of abdominal contraction (assessed by electromyography) in response to colorectal distension after the acute administration in DNBS-treated rats. Present findings showed that ABGE could represent a potential strategy for treatment of colitis-associated inflammatory process and visceral pain. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin.

Combining the Pharmaceutical and Toxicological Properties of Selected Essential Oils with their Chemical Components by GC-MS Analysis.

In the current investigation, a comprehensive analysis was carried out on essential oils (EOs) extracted from six aromatic plant species, namely Rosmarinus officinalis, Pelargonium graveolens, Thymus vulgaris, Origanum vulgare, Laurus nobilis, and Aloysia citrodora. An exploration was conducted into the chemical composition using Gas Chromatography-Mass Spectrometry (GC/MS), antioxidant properties assessed through DPPH, ABTS, CUPRAC, FRAP, MCA, and PBD assays, ecotoxicological impacts evaluated via allelopathy and the Daphnia magna heartbeat test, as well as bio-pharmacological effects including anticancer activity and gene expression analysis. Results revealed strong antioxidant activity in all essential oils, with T. vulgaris EO (2748.00 mg TE/g) and O. vulgare EO (2609.29 mg TE/g) leading in CUPRAC assay. R. officinalis EO showed the highest α-amylase inhibition at 1.58 mmol ACAE/g, while O. vulgare EO excelled in α-glucosidase inhibition at 1.57 mmol ACAE/g. Additionally, cytotoxic effects were evaluated on human colorectal cancer (HCT116) cells. A. citrodora, O. vulgare, and R. officinalis EOs were found the most potent anticancer, as also witnessed by their higher modulatory effects on the gene expression of BAX and Bcl-2. Collectively, the present data highlight the importance to implement the knowledge and to valorize the supply chain of aromatic plants.

Neuromodulatory Effects Induced by the Association of Moringa oleifera Lam., Tribulus terrestris L., Rhodiola rosea Lam., and Undaria pinnatidifida Extracts in the Hypothalamus.

The present study investigated the role of a commercial formulation constituted by herbal extracts from Rhodiola rosea, Undaria pinnatifida, Tribulus terrestris, and Moringa oleifera. The formulation was analysed for determining the content in total phenols and flavonoids and scavenging/reducing properties. The formulation was also tested on isolated mouse hypothalamus in order to investigate effects on serotonin, dopamine, neuropeptide Y (NPY), and orexin A. The gene expression of gonadrotopin releasing hormone (GnRH) was also assayed. The formulation was able to reduce dopamine and serotonin turnover, and this could be related, albeit partially, to the capability of different phytochemicals, among which hyperoside and catechin to inhibit monoaminooxidases activity. In parallel, the formulation was effective in reducing the gene expression of NPY and orexin-A and to improve the gene expression of GnRH. In this context, the increased GnRH gene expression induced by the formulation may contribute not only to improve the resistance towards the stress related to ageing, but also to prevent the reduction of libido that could be related with a stimulation of the serotoninergic pathway. According to the in silico analysis, hyperoside could play a pivotal role in modulating the gene expression of GnRH. Regarding NPY and orexin A gene expression, no direct interactions between the formulation phytochemicals and these neuropeptides were anticipated; thus, suggesting that the pattern of gene expression observed following exposure of the hypothalamus to the formulation may be secondary to inhibitory effects of dopamine and serotonin turnover. Concluding, the present study demonstrated the efficacy of the formulation in exerting neuromodulatory effects at the hypothalamic level; thus, suggesting the potential to contrast stress and fatigue.

Comprehensive metabolite and biological profile of "Sulmona Red Garlic" ecotype's aerial bulbils.

"Sulmona Red Garlic" is a well-known Italian traditional product. Bulbs, used for culinary purposes, have been largely investigated for their medicinal properties whereas aerial bulbils are usually removed as waste material. Here, for the first time, chemical composition and biological properties of the hydroalcoholic extract from aerial bulbils were investigated. Complementary information on metabolite composition were obtained using both NMR based untargeted and HPLC-DAD targeted methodologies. The NMR analysis revealed the presence of sugars, organic acids, amino acids, organosulphur compounds (methiin, alliin, allicin and cycloalliin), and other secondary metabolites. In particular, methiin and alliin were identified for the first time in the NMR spectra of aerial bulbil garlic extracts. Polyphenol content was determined by HPLC-DAD analysis: catechin, chlorogenic acid, and gallic acid turned out to be the most abundant phenolics. Hydroalcoholic extract blocked cell proliferation of colon cancer cell line HCT116 with an IC50 of 352.07 µg/mL, while it was non-toxic to myoblast cell line C2C12. In addition, it caused seedling germination reduction of two edible and herbaceous dicotyledon species, namely Cichorium intybus and C. endivia. Moreover, the same extract reduced the gene expression of TNF-α (tumor necrosis factor), HIF1-α (hypoxia-inducible factor), VEGFA (vascular endothelial growth factor), and transient receptor potential (TRP) M8 (TRPM8) indicating the ability to contrast cancer development through the angiogenic pathway. Final, in silico experiments were also carried out supporting the biological effects of organosulphur compounds, particularly alliin, which may directly interact with TRPM8. The results here reported suggest the potential use of garlic aerial bulbils often considered a waste product as a source in phytotherapeutic remedies.

Food Components in Health Promotion and Disease Prevention.

In recent years, more plant-based sources of functional foods have been shown to be effective in preventing, reducing, and treating chronic inflammatory and metabolic diseases, and promoting health [...].

Exploring for HPLC-MS/MS Profiles and Biological Activities of Different Extracts from Allium lycaonicum Siehe ex Hayek from Turkey Flora.

The present study was designed to determine the phenolic constituents, antioxidant, and enzyme inhibition activities of aerial parts and bulbs of Allium lycaonicum (family Amaryllidaceae). Extracts were prepared by maceration and Soxhlet/infusion using hexane, methanol, and water as extraction solvents. Generally, extracts from the aerial parts showed higher total phenolic and individual components and antioxidant activity than their respective bulb extracts. Maceration with water was the best to extract total phenolic content from the aerial parts (29.00 mg gallic acid equivalents (GAE)/g), while the Soxhlet extraction with hexane (22.29 mg GAE/g) was the best for the bulb. Maceration with methanol recovered the highest total flavonoid content from both the aerial parts (41.95 mg (rutin equivalents (RE)/g) and bulb (1.83 mg RE/g). Polar extracts of aerial parts were characterized by higher abundance of kaempferol-3-glucoside (≤20,624.27 µg/mg), hyperoside (≤19,722.76 µg/g), isoquercitrin (≤17,270.70 µg/g), delphindin-3,5-diglucoside (≤14,625.21 µg/g), and rutin (≤10,901.61 µg/g) than the bulb. Aerial parts' aqueous extract, prepared by maceration, exerted the highest anti-ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical activity (64.09 mg trolox equivalents (TE)/g), Cu++ (83.03 mg TE/g) and Fe+++ (63.03 mg TE/g) reducing capacity while that prepared by infusion recorded the highest anti-DPPH (2,2-diphenyl-1-picrylhydrazyl) radical (31.70 mg TE/g) and metal chelating (27.66 mg EDTAE/g) activities. The highest total antioxidant activity (1.46 mmol TE/g) was obtained by maceration of the bulb with water. Extracts obtained by organic solvents showed remarkable enzyme inhibition properties against the tested enzymes. Soxhlet extraction of the bulb with hexane and methanol recorded the highest acetylcholinesterase inhibition (4.75 mg galanthamine equivalents (GALAE)/g) and tyrosinase inhibition (139.95 mg kojic acid equivalents/g) activities, respectively. Extracts obtained by maceration of the bulb with methanol and the aerial parts with hexane exerted the highest glucosidase inhibition (3.25 mmol acarbose equivalents/g) and butyrylcholinesterase inhibition (20.99 mg GALAE/g) activities, respectively. These data indicated that A. lycaonicum is a source of bioactive molecules with potential antioxidant and enzyme inhibition properties. Nonetheless, the extracts obtained through various solvents and extraction techniques showed variations in their phytoconstituent composition and biological properties.

Effects of GHRH Deficiency and GHRH Antagonism on Emotional Disorders in Mice.

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.

Screening for Chemical Characterization and Pharmacological Properties of Different Extracts from Nepeta italica.

Plants from the Nepeta genus have been proved to possess different pharmacological properties, among which are antimicrobial, antioxidant, anti-inflammatory, analgesic, and cytotoxic effects. Nepeta italica is a medicinal plant traditionally used for its analgesic effects, and in the present study, the phytochemical composition and biological effects of hexane, dichloromethane (DCM), ethyl acetate (EA), ethanol, ethanol-water, and water extracts of the aerial parts were investigated for determining phenolic composition, antioxidant effects, and anti-inflammatory effects in isolated mouse colon specimens exposed to lipopolysaccharide (LPS). Polar extracts were the richest in terms of phenolic compounds, especially rosmarinic acid. In parallel, ethanol, ethanol-water, and water extracts were also the most effective as scavenging/reducing and enzyme inhibition agents, especially towards cholinesterases and α-glucosidase, and in inhibiting the LPS-induced cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) gene expression in mouse colon. This poses the basis for future in vivo investigations for confirming the protective effects of polar extracts of N. italica against inflammatory bowel diseases.

Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant, Enzyme Inhibitory and Anti-Inflammatory Properties.

Artemisia annua L. (Asteraceae Family) is an important plant in Asia that has been used for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts (hexane, dichloromethane, ethyl acetate, ethanol, ethanol/water (70 %) and water) from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. The water extract contained the highest content of the total phenolic with 34.59 mg gallic acid equivalent (GAE)/g extract, while the hexane had the highest content of the total flavonoid (20.06 mg rutin equivalent (RE)/g extract). In antioxidant assays, the polar extracts (ethanol, ethanol/water and water) exhibited stronger radical scavenging and reducing power abilities when compared to non-polar extracts. The hexane extract showed the best AChE, tyrosinase and glucosidase inhibitory effects. All extracts revealed effective anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.

Anti-Inflammatory and Vasorelaxant Effects Induced by an Aqueous Aged Black Garlic Extract Supplemented with Vitamins D, C, and B12 on Cardiovascular System.

Multiple studies demonstrated biological activities of aged black garlic, including anti-inflammatory, antioxidant, and cardioprotective effects. We aimed to investigate the protective effects of an aged black garlic water extract (ABGE) alone or in association with multivitamins consisting of combined Vitamins D, C, and B12, on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS). Moreover, we studied the hydrogen sulphide (H2S) releasing properties and the membrane hyperpolarization effect of the Formulation composed by ABGE and multivitamins, using Human Aortic Smooth Muscle Cells (HASMCs). ABGE, vitamins D and C, and the Formulation suppressed LPS-induced gene expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor-kB (NF-kB), and inducible nitric oxide synthase (iNOS) on mouse heart specimens. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin. The Formulation also increased fluorescence values compared to the vehicle, and it caused a significant membrane hyperpolarization of HASMCs compared to ABGE. To conclude, our present findings showed that ABGE, alone and in association with multivitamins, exhibited protective effects on mouse heart. Moreover, the Formulation increased intracellular H2S formation, further suggesting its potential use on cardiovascular disease.

Anti-Inflammatory, Antioxidant, and WAT/BAT-Conversion Stimulation Induced by Novel PPAR Ligands: Results from Ex Vivo and In Vitro Studies.

Activation of peroxisome proliferator-activated receptors (PPARs) not only regulates multiple metabolic pathways, but mediates various biological effects related to inflammation and oxidative stress. We investigated the effects of four new PPAR ligands containing a fibrate scaffold-the PPAR agonists (1a (αEC50 1.0 µM) and 1b (γEC50 0.012 µM)) and antagonists (2a (αIC50 6.5 µM) and 2b (αIC50 0.98 µM, with a weak antagonist activity on γ isoform))-on proinflammatory and oxidative stress biomarkers. The PPAR ligands 1a-b and 2a-b (0.1-10 µM) were tested on isolated liver specimens treated with lipopolysaccharide (LPS), and the levels of lactate dehydrogenase (LDH), prostaglandin (PG) E2, and 8-iso-PGF2α were measured. The effects of these compounds on the gene expression of the adipose tissue markers of browning, PPARα, and PPARγ, in white adipocytes, were evaluated as well. We found a significant reduction in LPS-induced LDH, PGE2, and 8-iso-PGF2α levels after 1a treatment. On the other hand, 1b decreased LPS-induced LDH activity. Compared to the control, 1a stimulated uncoupling protein 1 (UCP1), PR-(PRD1-BF1-RIZ1 homologous) domain containing 16 (PRDM16), deiodinase type II (DIO2), and PPARα and PPARγ gene expression, in 3T3-L1 cells. Similarly, 1b increased UCP1, DIO2, and PPARγ gene expression. 2a-b caused a reduction in the gene expression of UCP1, PRDM16, and DIO2 when tested at 10 µM. In addition, 2a-b significantly decreased PPARα gene expression. A significant reduction in PPARγ gene expression was also found after 2b treatment. The novel PPARα agonist 1a might be a promising lead compound and represents a valuable pharmacological tool for further assessment. The PPARγ agonist 1b could play a minor role in the regulation of inflammatory pathways.

Adding New Scientific Evidences on the Pharmaceutical Properties of Pelargonium quercetorum Agnew Extracts by Using In Vitro and In Silico Approaches.

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.

New Biological and Chemical Evidences of Two Lamiaceae Species (Thymbra capitata and Thymus sipyleus subsp. rosulans): In Vitro, In Silico and Ex Vivo Approaches.

In this study, the methanolic and infusion extracts of two species, Thymbra capitata and Thymus sipyleus subsp. rosulans, were tested for their chemical composition and biological abilities (antioxidant, enzyme inhibitory and anti-inflammatory effects). The extracts yielded total phenolic and flavonoid contents in the range of 83.43-127.52 mg GAE/g and 9.41-46.34 mg RE/g, respectively. HPLC analysis revealed rosmarinic acid to be a major component of the studied extracts (15.85-26.43%). The best ABTS radical scavenging ability was observed in the methanol extract of T. capitata with 379.11 mg TE/g, followed by in the methanol extract of T. sipylus (360.93 mg TE/g). In the CUPRAC assay, the highest reducing ability was also found in the methanol extract of T. capitata with 802.22 mg TE/g. The phosphomolybdenum ability ranged from 2.39 to 3.61 mmol TE/g. In terms of tyrosinase inhibitory effects, the tested methanol extracts (83.18-89.66 mg KAE/g) were higher than the tested water extracts (18.74-19.11 mg KAE/g). Regarding the BChE inhibitory effects, the methanol extracts were active on the enzyme while the water extracts showed no inhibitory effect on it. Overall, the methanolic extracts showed better enzyme inhibition compared to the infusion extracts. Molecular docking also showed the selected exhibited potential binding affinities with all enzymes, with a preference for cholinesterases. Additionally, the extracts were effective in attenuating the LPS-induced increase in COX-2 and IL-6 gene expression in isolated colon, thus indicating promising anti-inflammatory effects. The preliminary results of this study suggest that these species are good natural sources of antioxidants and also provide some scope as enzyme inhibitors, most likely due to their bioactive contents such as phenolic acids, and thus can be exploited for different applications related to health promotion and disease prevention.

Anti-Inflammatory and Antioxidant Effects Induced by Allium sativum L. Extracts on an Ex Vivo Experimental Model of Ulcerative Colitis.

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.

Phytochemical and biological investigations on the pollen from industrial hemp male inflorescences.

Cannabis sativa L. belongs to the Cannabaceae family and includes annual, robust, fast-growing and generally dioecious plants. Industrial hemp, and particularly the inflorescences, has been recently recognized as important source of bioactive extracts with antioxidant and antimicrobial effects. The goal of the present study was to explore botanical, phytochemical, and biological properties of water and hydroalcoholic hemp pollen extracts from male inflorescences. The extracts from hemp pollen were found rich in phenolic compounds, such as hydroxytyrosol, coumaric acid, and hesperitin. The phenolic profile was also consistent with the observed scavenging/reducing, enzyme inhibitory, and antimicrobial properties of the extracts. Regarding the antimicrobial effects, Escherichia coli, Trycophyton rubrum, and T. tonsurans were the most sensitive to growth inhibitory effects (MIC values: 9.92-79.37 µg/mL) of the extracts. Whereas, null effects on prostate PC3 and myocyte C2C12 cell viability, in the range 1-1000 µg/mL, are consistent with MIC values and suggest extracts' biocompatibility. The experimental data obtained, which are not reflected in the literature as the topic of hemp pollen is almost completely unexplored, confirm the innovativeness of a product obtained directly from bees, which in the face of greater variability and complexity can reserve promising applications in food, pharmaceutical, and cosmetic sectors.

Protective Effects of PollenAid Plus Soft Gel Capsules' Hydroalcoholic Extract in Isolated Prostates and Ovaries Exposed to Lipopolysaccharide.

Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract's cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.

A grape (Vitis vinifera L.) pomace water extract modulates inflammatory and immune response in SW-480 cells and isolated mouse colon.

Grape (Vitis vinifera L.) pomace is a residue derived from the winemaking process, which contains bioactive compounds displaying noteworthy health-promoting properties. The aim of the present study was to investigate the phenolic composition and protective effects of a water extract of grape pomace (WEGP) in colorectal cancer cell line SW480 and in isolated mouse colon exposed to Escherichia coli lipopolysaccharide (LPS). The extract decreased SW-480 cell viability, as well as vascular endothelial factor A (VEGFA), hypoxia-induced factor 1α (HIF1α), and transient receptor potential M8 (TRPM8) LPS-induced gene expression. Moreover, the extract inhibited mRNA levels of nuclear factor kB (NFkB), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-1ß, IL-10, inducible nitric oxide synthase (iNOS), and interferon (IFN)γ, in isolated colon. Conversely, WEGP increased the gene expression of antioxidant catalase (CAT) and superoxide dismutase (SOD), in the same model. The modulatory effects exerted by WEGP could be related, at least in part, to the phenolic composition, with particular regards to the catechin level. Docking calculations also predicted the interactions of catechin toward TRPM8 receptor, deeply involved in colon cancer; thus further suggesting the grape pomace as a valuable source of bioactive extracts and phytochemicals with protective effects in the colon.