Publications by authors named "Claudio Ferrante"

81 Publications

Comparative Investigation of Composition, Antifungal, and Anti-Inflammatory Effects of the Essential Oil from Three Industrial Hemp Varieties from Italian Cultivation.

Antibiotics (Basel) 2021 Mar 22;10(3). Epub 2021 Mar 22.

Department of Pharmacy, Botanic Garden "Giardino dei Semplici", Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) of , and hemp varieties. The EOs were also tested for antifungal properties toward and . In parallel, we investigated the inhibitory effects of the EOs against tyrosinase, and the production of prostaglandin E in isolated mouse skin exposed to hydrogen peroxide. In human H1299 lung adenocarcinoma cells, we also evaluated the influence of the EOs on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are involved in SARS-CoV-2 entry in human host. -caryophyllene and α-pinene were the prominent terpenes in the EOs, whereas the cannabidiolic acid was the terpenophenol present at higher concentration. The EOs inhibited the growth of all tested dermatophytes species. In isolated skin specimens, EOs prevented the hydrogen-peroxide-induced synthesis of prostaglandin E, consistent with the intrinsic antityrosinase activity. Finally, in H1299 cells, all tested EOs reduced the gene expression of ACE-2 and TMPRSS2, as well. Therefore, the present findings highlight the rationale for the use of the present EOs against infectious diseases.
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http://dx.doi.org/10.3390/antibiotics10030334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005080PMC
March 2021

Chemical and Bioinformatics Analyses of the Anti-Leishmanial and Anti-Oxidant Activities of Hemp Essential Oil.

Biomolecules 2021 Feb 12;11(2). Epub 2021 Feb 12.

Department of Pharmacy, University of Lahore, Islamabad Campus, Islamabad 54590, Pakistan.

Industrial hemp is a multiuse crop that has been widely cultivated to produce fibers and nutrients. The capability of the essential oil (EO) from inflorescences as antimicrobial agent has been reported. However, literature data are still lacking about the hemp EO antiprotozoal efficacy in vivo. The present study aims to unravel this concern through the evaluation of the efficacy of hemp EOs (2.5 mL/kg, intraperitoneally) of three different cultivars, namely , and , in mice intraperitoneally infected with . A detailed description of EO composition and targets-components analysis is reported. Myrcene, α-pinene and -caryophyllene were the main components of the EOs, as indicated by the gas-chromatographic analysis. However, a prominent position in the scenario of the theoretical interactions underlying the bio-pharmacological activity was also occupied by selina-3,7(11)-diene, which displayed affinities in the micromolar range (5.4-28.9) towards proliferator-activated receptor α, cannabinoid CB2 receptor and acetylcholinesterase. The content of this compound was higher in and , in accordance with their higher scavenging/reducing properties and efficacy against the tissue wound, induced by . Overall, the present study recommends hemp female inflorescences, as sources of biomolecules with potential pharmacological applications, especially towards infective diseases.
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http://dx.doi.org/10.3390/biom11020272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917915PMC
February 2021

Pharmacological Potential and Chemical Characterization of Benth.-A Native Tropical African Medicinal Plant.

Antibiotics (Basel) 2021 Feb 23;10(2). Epub 2021 Feb 23.

Department of Life Sciences and Biotechnology (SVeB), UR7 Terra&Acqua Tech, University of Ferrara, 44121 Ferrara, Italy.

To avail the possible pharmacological actions of Benth., the present investigation was designed to quantitatively analyze the total flavonoid and phenolic contents and assess the various antioxidant and enzyme inhibition properties of leaf and stem bark extracts (ethyl acetate, water and methanolic) of Anti-proliferative effect was also investigated against human colon cancer cells (HCT116) as well as the antimicrobial potential against multiple bacterial and fungal (yeasts and dermatophytes) strains. The methanolic and water extracts of the stem bark demonstrated the highest phenolic content (193.58 ± 0.98 and 187.84 ± 1.88 mg/g, respectively), while the leaf extracts showed comparatively higher flavonoid contents (24.37-42.31 mg/g). Overall, the methanolic extracts were found to possess the most significant antioxidant potency. Compared to the other extracts, methanolic extracts of the were revealed to be most potent inhibitors of acetyl- and butyryl-cholinesterases, tyrosinase -amylase, except -glucosidase. Only the ethyl acetate extracts were found to inhibit glucosidase. Additionally, the stem bark methanolic extract also showed potent inhibitory activity against and gram-positive bacteria (MIC (minimum inhibitory concentration): 2.48-62.99 µg/mL), as well as all the tested fungi (MIC: 4.96-62.99 µg/mL). In conclusion, can be regarded as a promising source of bioactive compounds displaying multifunctional pharmacological activities and thus is a potential candidate for further investigations in the endeavor to develop botanical formulations for pharmaceutical and cosmeceutical industries.
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http://dx.doi.org/10.3390/antibiotics10020223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926895PMC
February 2021

Deeper Insights on (Schumach. & Thonn.) Müll.Arg Extracts: Chemical Profiles, Biological Abilities, Network Analysis and Molecular Docking.

Biomolecules 2021 Feb 4;11(2). Epub 2021 Feb 4.

Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey.

(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 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 to be a species worthy of further investigations, given its richness in bioactive phytochemicals and wide potentialities for antioxidants and pharmacological agents.
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http://dx.doi.org/10.3390/biom11020219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913913PMC
February 2021

Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice.

Sci Rep 2021 Jan 28;11(1):2530. Epub 2021 Jan 28.

Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.

Besides its metabolic and endocrine effects, growth hormone (GH)-releasing hormone (GHRH) is involved in the modulation of inflammation. Recently synthetized GHRH antagonist MIA-690 and MR-409, GHRH agonist, developed by us have shown potent pharmacological effects in various experimental paradigms. However, whether their administration modify resistance to chronic inflammatory stimuli in colon is still unknown. Ex vivo results demonstrated that MIA-690 and MR-409 inhibited production of pro-inflammatory and oxidative markers induced by lipopolysaccharide on isolated mouse colon specimens. In vivo, both MIA-690 and MR-409 have also been able to decrease the responsiveness to nociceptive stimulus, in hot plate test. Additionally, both peptides also induced a decreased sensitivity to acute and persistent inflammatory stimuli in male mice, in formalin test and dextran sodium sulfate (DSS)-induced colitis model, respectively. MIA-690 and MR-409 attenuate DSS-induced colitis with particular regard to clinical manifestations, histopathological damage and release of pro-inflammatory and oxidative markers in colon specimens. Respect to MR-409, MIA-690 showed higher efficacy in inhibiting prostaglandin (PG)E, 8-iso-PGF and serotonin (5-HT) levels, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide synthase gene expression in colon specimens of DSS-induced colitis. Furthermore, MIA-690 decreased serum insulin-like growth factor (IGF)-1 levels in mice DSS-treated, respect to MR-409. Thus, our findings highlight the protective effects of MIA-690 and MR-409 on inflammation stimuli. The higher antinflammatory and antioxidant activities observed with MIA-690 could be related to decreased serum IGF-1 levels.
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http://dx.doi.org/10.1038/s41598-021-81778-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844299PMC
January 2021

Bioactivity assays, chemical characterization, ADMET predictions and network analysis of Khaya senegalensis A. Juss (Meliaceae) extracts.

Food Res Int 2021 Jan 8;139:109970. Epub 2020 Dec 8.

Department of Analytical Chemistry, University of Granada, C/Fuentenueva s/n, 18071 Granada, Spain; Research and Development of Functional Food Centre (CIDAF), PTS Granada, Avda. Del Conocimiento s/n., Edificio BioRegion, 18016 Granada, Spain.

Khaya senegalensis A. Juss (Meliaceae) is a popular medicinal plant, widely used in the management of various ailments in the African traditional medicine. This study attempts to investigate into the different extraction methods (homogenizer-assisted extraction (HAE), maceration (MAC), infusion and Soxhlet (SE) extraction) on the pharmacological properties and chemical profiles of K. senegalensis. Antioxidant properties and inhibitory potential against key enzymes were assessed and bioinformatics analysis was conducted on selected limonoids to predict putative pharmacokinetics and protein targets underlying the pharmacological effects. Overall, the leaf extracts showed notable flavonoid (20.59-104.43 mg RE/g) content and the stem barks extracts displayed the highest total phenolic (87.69-46.28 mg GAE/g), phenolic acid (62.96-107.22 mg CE/g), flavanol (3.60-135.40 mg CAE/g) contents. All extracts showed remarkable antioxidant activities, with the MAC-Water leaf extract being most active in all the assays. Regarding stem bark, the MAC-MeOH extract exerted the highest free radical scavenging abilities, while HAE and MAC extracts were better sources of reducing agent and metal chelators. The HAE-MeOH, MAC-Water, and SE extracts showed noteworthy inhibitory activity against AChE, BChE (only stem barks), tyrosinase and α-glucosidase (only stem barks). All extracts displayed moderate inhibitory activities against α-amylase. The bioinformatics approach showed that khayanoside A and C interacted with multiple isoforms of metalloproteinase, while humilin B and khayanone interacted with opioid receptors. To sum up, the chemical profiles and biological activities of K. senegalensis were closely dependent on the extraction methods. Results amassed from this study showed that K. senegalensis is a potent source of bioactive compounds which could be explored as a functional food.
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http://dx.doi.org/10.1016/j.foodres.2020.109970DOI Listing
January 2021

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens.

Antioxidants (Basel) 2021 Jan 1;10(1). Epub 2021 Jan 1.

Department of Pharmacy, Università Degli Studi "Gabriele d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.

Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1-500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.
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http://dx.doi.org/10.3390/antiox10010044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823476PMC
January 2021

Anti-Inflammatory and Neuromodulatory Effects Induced by Water Extract: Results from In Silico, In Vitro and Ex Vivo Studies.

Molecules 2020 Dec 23;26(1). Epub 2020 Dec 23.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

(feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K 60 mM Krebs-Ringer buffer and treated with water extract. The prostaglandin E (PGE) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1β gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE release and IL-1β gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.
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http://dx.doi.org/10.3390/molecules26010022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793142PMC
December 2020

Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways.

Int J Mol Sci 2020 Dec 21;21(24). Epub 2020 Dec 21.

Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria.

Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.
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http://dx.doi.org/10.3390/ijms21249740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766967PMC
December 2020

Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases.

Front Physiol 2020 30;11:578966. Epub 2020 Oct 30.

Department of Pharmacy, Gabriele d'Annunzio University, Chieti, Italy.

Besides its role as an energy storage organ, adipose tissue can be viewed as a dynamic and complex endocrine organ, which produces and secretes several adipokines, including hormones, cytokines, extracellular matrix (ECM) proteins, and growth and vasoactive factors. A wide body of evidence showed that adipokines play a critical role in various biological and physiological functions, among which feeding modulation, inflammatory and immune function, glucose and lipid metabolism, and blood pressure control. The aim of this review is to summarize the effects of several adipokines, including leptin, diponectin, resistin, chemerin, lipocalin-2 (LCN2), vaspin, omentin, follistatin-like 1 (FSTL1), secreted protein acidic and rich in cysteine (SPARC), secreted frizzled-related protein 5 (SFRP5), C1q/TNF-related proteins (CTRPs), family with sequence similarity to 19 member A5 (FAM19A5), wingless-type inducible signaling pathway protein-1 (WISP1), progranulin (PGRN), nesfatin-1 (nesfatin), visfatin/PBEF/NAMPT, apelin, retinol binding protein 4 (RPB4), and plasminogen activator inhibitor-1 (PAI-1) in the regulation of insulin resistance and vascular function, as well as many aspects of inflammation and immunity and their potential role in managing obesity-associated diseases, including metabolic, osteoarticular, and cardiovascular diseases.
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http://dx.doi.org/10.3389/fphys.2020.578966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662468PMC
October 2020

Phenolic Content and Antimicrobial and Anti-Inflammatory Effects of , , , , and Extracts.

Antibiotics (Basel) 2020 Nov 6;9(11). Epub 2020 Nov 6.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

Prostatitis is an inflammatory condition that is related to multiple infectious agents, including bacteria and fungi. Traditional herbal extracts proved efficacious in controlling clinical symptoms associated with prostatitis. In this context, the aim of the present study was to explore the efficacy of extracts from , , , and against bacterial () and fungi strains () involved in prostatitis. Additionally, anti-mycotic effects were tested against multiple species of dermatophytes (, and ). Antioxidant effects were also evaluated in isolated rat prostates challenged with lipopolysaccharide (LPS), and phytochemical analyses were conducted to identify and quantify selected phenolic compounds, in the extracts. Finally, a bioinformatics analysis was conducted to predict putative human and microbial enzymes targeted by extracts' phytocompounds and underlying the observed bio-pharmacological effects. The phytochemical analysis highlighted that rutin levels could be crucial for explaining the highest antibacterial activity of extract, especially against and . On the other hand, in the extract, catechin concentration could partially explain the highest efficacy of this extract in reducing lipid peroxidation, in isolated rat prostates stimulated with LPS. Concluding, the results of the present study showed moderate antimicrobial and anti-inflammatory effects induced by water extracts of , and that could be related, at least partially, to the phenolic composition of the phytocomplex.
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http://dx.doi.org/10.3390/antibiotics9110783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694769PMC
November 2020

Network analysis, chemical characterization, antioxidant and enzyme inhibitory effects of foxglove (Digitalis cariensis Boiss. ex Jaub. & Spach): A novel raw material for pharmaceutical applications.

J Pharm Biomed Anal 2020 Nov 16;191:113614. Epub 2020 Sep 16.

Department of Pharmacy, "G. d'Annunzio University" Chieti-Pescara, Via dei Vestini n. 31, 66100 Chieti, Italy.

The present study outlines the phenolic composition and pharmacological properties of different extracts of Digitalis cariensis Boiss. ex Jaub. & Spach root and aerial parts. The metabolic profiles of the studied extracts were characterized by UHPLC-MS. The in vitro antioxidant and enzyme (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase) inhibitory potential of the extracts were determined. Bioinformatics and docking investigations were also conducted to support the enzyme inhibition test and predict putative targets for potential pharmacological applications. Overall, the methanolic extract followed by the water extract of the D. cariensis root were found to be superior source of antioxidant compounds except for metal chelating ability, in which the water extract of the root (26.34 ± 1.54 mg EDTAE/g) and aerial parts (16.47 ± 0.88 mg EDTAE/g) have showed the highest activity. The tested extracts were potent against AChE (9.11 ± 0.27-9.79 ± 0.28 mg GEs/g extract), α-amylase (0.12 ± 0.01- 0.50 ± 0.01 mmol ACEs/g extract) and α-glucosidase (0.28 ± 0.01-17.29 ± 0.24 mmol ACEs/ g extract). Notable activity against tyrosinase was displayed by the methanolic extracts (Root-MeOH: 123.71 ± 2.70 and aerial parts - MeOH: 137.96 ± 1.07 mg KAE/g extract), while none of the extracts were potent against BChE. According to docking investigations, the observed anti-tyrosinase effect could be related, at least partially, to the presence of luteolin, rosmarinic acid and kaempferol in the extracts. Results amassed herein is the first report on the biological attributes of D. cariensis, which validate the pharmacological uses of this plant.
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http://dx.doi.org/10.1016/j.jpba.2020.113614DOI Listing
November 2020

Antimicrobial, Antioxidant, and Antiproliferative Effects of : An Unexplored Botanical Species.

Antibiotics (Basel) 2020 Sep 17;9(9). Epub 2020 Sep 17.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

species, belonging to the genus (Fabaceae), have long been used in traditional medicine for treating cold, diabetes, pain, and as cardiotonics. The goal of the present study was to explore the phytochemical composition and pharmaco-toxicological properties of In this regard, phenolic content, scavenging/reducing properties and antimicrobial activity toward pathogen bacterial (, , , ) and fungal strains (, , and ) were investigated. Extract effects on human colon cancer HCT116 cell viability were also assayed. Finally, a bioinformatics approach was conducted with the aim to identify putative microbial and human protein targets underlying antibacterial, antimycotic, and antiproliferative effects. Phytochemical investigation suggested that water extract is richer in terms of total flavonoid and phenol content, whereas the hydroalcoholic extract was revealed to be more potent as antioxidant agent. According to bioinformatics analysis, the antibacterial activity of the hydroalcoholic extract could be related to its content in resveratrol. The presence of resveratrol could also explain the hydroalcoholic extract efficacy in reducing HCT116 cell viability. In conclusion, the present study represents the first phytochemical and bio-pharmacological investigation about . Like other plants belonging to the Fabaceae family, revealed a good source of resveratrol, which could explain, albeit partially, the efficacy of the hydroalcoholic extract as antimicrobial, antioxidant, and antiproliferative agent.
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http://dx.doi.org/10.3390/antibiotics9090611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560210PMC
September 2020

Hop Extract: An Efficacious Antimicrobial and Anti-biofilm Agent Against Multidrug-Resistant Staphylococci Strains and .

Front Microbiol 2020 13;11:1852. Epub 2020 Aug 13.

LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.

Bacteria belonging to genus, in particular methicillin-resistant and multidrug-resistant , together with are the main strains involved in skin disease. The increase in multidrug-resistant bacteria has revived attention on natural compounds as alternative agents for the treatment management. Among these, hop extract, a hydroalcoholic solution obtained from experimental crops of L. variety (hop), displays diverse biological properties including an antimicrobial one. The aim of this study was to evaluate the antimicrobial activity and the capacity to inhibit the biofilm formation of a characterized hop extract against and multidrug-resistant strains and against a strain. The hop extract was characterized by (i) phytochemical analysis through a reversed-phase high-performance liquid chromatography (HPLC)-fluorimetric method, (ii) biocompatibility test with L., (iii) cytotoxicity against two cell lines, (iv) docking analysis, and (v) antimicrobial and antibiofilm activities by detection of zones inhibition, minimal inhibitory concentrations (MICs), biomass quantification, and cell viability. The hop extract was biocompatible and non-cytotoxic at all tested concentrations. HPLC analysis revealed significant levels of gallic acid, resveratrol, and rutin. This last compound was the most representative displaying a high affinity against PBP2a and KAS III (Ki values in the submicromolar range). The characterized hop extract showed a good antimicrobial action with MICs ranging from 1 to 16 μg/mL and was able to inhibit the biofilm formation of all tested strains, except for two strains. The biofilm formed in presence of the hop extract was significantly reduced in most cases, even when present at a concentration of 1/4 MIC. The live/dead images showed a remarkable inhibition in the biofilm formation by hop extract with a weak killing action. Overall, the tested hop extract is a good candidate to further explore for its use in the prevention of infection particularly, by multidrug-resistant Gram-positive pathogens.
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http://dx.doi.org/10.3389/fmicb.2020.01852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438819PMC
August 2020

Evaluation of Antioxidant, Antimicrobial and Tyrosinase Inhibitory Activities of Extracts from an Edible Wild Mushroom.

Antibiotics (Basel) 2020 Aug 13;9(8). Epub 2020 Aug 13.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

(Bres.) Guzmán ex T.J. Baroni is an excellent edible mushroom whose compounds and biological properties are still unknown. In this study, n-hexane, ethyl acetate and methanol extracts from fruiting bodies and liquid-cultured mycelia were compared for the analysis of phenolic compounds, the evaluation of scavenger (DPPH, ABTS) and reducing (CUPRAC, FRAP) activities, and the enzyme inhibition of α-amylase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase. Additionally, extracts were evaluated for antibacterial and antimycotic activities against Gram+ and Gram- bacteria, and clinical yeast and fungal dermatophytes. Finally, based on the extract content in phenolic compounds, in silico studies, including the docking approach, were conducted to predict the putative targets (namely tyrosinase, lanosterol-14-α-demethylase, the multidrug efflux system transporters of (mdtK) and (pmpM), and β-lactamase (ORF259)) underlying the observed bio-pharmacological and microbiological effects. The methanolic extract from mycelia was the richest in gallic acid, whereas the ethyl acetate extract from fruiting bodies was the sole extract to show levels of catechin. Specifically, docking runs demonstrated an affinity of catechin towards all docked proteins, in the micromolar range. These in silico data are consistent, at least in part, with the highest activity of ethyl acetate extract as an antimicrobial and anti-tyrosinase (554.30 mg KAE/g for fruiting bodies and 412.81 mg KAE/g for mycelia) agent. The ethyl acetate extracts were also noted as being the most active (2.97 mmol ACAE/g for fruiting bodies and 2.25 mmol ACAE/g for mycelia) on α-amylase. BChE inhibitory activities varied from 2.61 to 26.78 mg GALAE/g, while the tested extracts were not active on AChE. In conclusion, all mushroom extracts tested in this study had potent antimicrobial activities. Particularly, among the tested extracts, the ethyl acetate extract showed the highest efficacy as both an antimicrobial and anti-tyrosinase agent. This could be related, albeit partially, to its content of catechin. In this regard, the bioinformatics analyses showed interactions of catechin with tyrosinase and specific microbial proteins involved in the resistance to chemotherapeutic drugs, thus suggesting innovative pharmacological applications of extracts.
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http://dx.doi.org/10.3390/antibiotics9080513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460263PMC
August 2020

Effect of high-altitude trekking on blood pressure and on asymmetric dimethylarginine and isoprostane production: Results from a Mount Ararat expedition.

J Clin Hypertens (Greenwich) 2020 08 6;22(8):1494-1503. Epub 2020 Aug 6.

Department of Cardiovascular Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano, Milan, Italy.

The study aimed at exploring the mechanisms behind blood pressure and heart rate changes upon acute altitude exposure utilizing urinary excretion of biochemical factors involved in cardiovascular regulation. The study was conducted on 12 lowlander native male mountain climbers, living at sea level, exposed to altitudes ranging from 1800 to 5147 m above sea level over 4 days, during their ascent to Mount Ararat (Turkey). Blood pressure (measured by oscillometric method), heart rate, and blood oxygen saturation (SpO ) were recorded at rest (on awakening before food intake), in hypoxic conditions at 4200 m and at sea level before and after the altitude expedition. In the same study conditions (ie before-during-after the expedition), first-voided urinary samples were collected and assayed for 8-iso-prostaglandin F (8-iso-PGF ) and asymmetric dimethylarginine (ADMA) determination. Heart rate, and systolic and diastolic blood pressures were higher (P < .05) at high altitude than at the sea level. Furthermore, both urinary 8-iso-PGF and ADMA were significantly elevated (P < .01) at high altitude and returned to normal levels soon after returning to sea level. A 4-day exposure to high-altitude hypoxia induced a temporary increase in blood pressure and heart rate, confirming previous findings. Blood pressure increase at high altitude was associated with significantly enhanced production of biochemical mediators such as 8-iso-PGF2α, catecholamines, and ADMA, although we could not demonstrate a direct link between these parallel significant changes probably due to the forcefully limited sample size of our study, carried out in challenging environmental conditions at very high altitude.
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http://dx.doi.org/10.1111/jch.13961DOI Listing
August 2020

Identification of Chemical Profiles and Biological Properties of G. Mey. Extracts Obtained by Different Methods and Solvents.

Antioxidants (Basel) 2020 Jun 18;9(6). Epub 2020 Jun 18.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

Mangrove forests exemplify a multifaceted ecosystem since they do not only play a crucial ecological role but also possess medicinal properties. Methanolic, ethyl acetate and aqueous leaf and bark extracts were prepared using homogenizer-assisted extraction (HAE), infusion and maceration (with and without stirring). The different extracts were screened for phytochemical profiling and antioxidant capacities in terms of radical scavenging (DPPH, ABTS), reducing potential (CUPRAC, FRAP), total antioxidant capacity and chelating power. Additionally, was evaluated for its anti-diabetic (α-amylase, α-glucosidase), anti-tyrosinase and anti-cholinesterase (AChE, BChE) activities. Additionally, antimycotic and antibacterial effects were investigated against and . Finally, based on phytochemical fingerprint, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted to predict the putative targets, namely tyrosinase, lanosterol-14-α-demethylase and DNA gyrase, underlying the observed bio-pharmacological and microbiological effects. The methanolic leave and bark extracts (prepared by both HAE and maceration) abounded with phenolics, flavonoids, phenolic acids and flavonols. Results displayed that both methanolic leaf and bark extracts (prepared by HAE) exhibited the highest radical scavenging, reducing potential and total antioxidant capacity. Furthermore, our findings showed that the highest enzymatic inhibitory activity recorded was with the tyrosinase enzyme. In this context, bioinformatics analysis predicted putative interactions between tyrosinase and multiple secondary metabolites including apigenin, luteolin, vitexin, isovitexin, procyanidin B, quercetin and methoxy-trihydroxyflavone. The same compounds were also docked against lanosterol-14α-demethylase and DNA gyrase, yielding affinities in the submicromolar-micromolar range that further support the observed anti-microbial effects exerted by the extracts. In conclusion, extracts of may be considered as novel sources of phytoanti-oxidants and enzyme inhibitors that can be exploited as future first-line pharmacophores.
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http://dx.doi.org/10.3390/antiox9060533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346144PMC
June 2020

Phytochemical Analysis, Network Pharmacology and in Silico Investigations on Tuber Extracts.

Molecules 2020 May 22;25(10). Epub 2020 May 22.

Department of Pharmacy, "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.

(L.) Rich. forms part of the Orchidaceae family that is highlyvalued for its horticultural as well as therapeutic benefits. The present study set out to investigatethe inhibitory activity of tubers against key biological targets for the management oftype 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidantpotential of the extracts was also assessed using multiple methods. The detailed phytochemicalprofiles of the extracts were determined using high-performance liquid chromatography. Based onqualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well.Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivativeswere present in the methanol extract. The methanol extract exhibited high inhibitory activityagainst tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarboseequivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, themethanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Troloxequivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC),and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results ofnetwork pharmacology analysis, besides corroborating traditional uses of plant extracts in themanagement of cold and flu, confirmed a direct involvement of identified phytochemicals in theobserved enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase.Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of extracts and identified phytocompounds on enzymesinvolved in type 2 diabetes, a docking study was conducted in order to investigate the putativeinteractions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldosereductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV,and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds againstthe aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxyoctadecenoic acid. Overall, the present findings supported the rationale for the use of as source of bioactive metabolites and highlight, today more than ever, for the strongnecessity of linkage strategy between wild resource valorization and conservation policy.
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http://dx.doi.org/10.3390/molecules25102422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288046PMC
May 2020

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes.

Int J Mol Sci 2020 05 18;21(10). Epub 2020 May 18.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

Cannabidiol (CBD) and cannabigerol (CBG) are 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. 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.
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http://dx.doi.org/10.3390/ijms21103575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279038PMC
May 2020

Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies.

Antioxidants (Basel) 2020 May 17;9(5). Epub 2020 May 17.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

Industrial hemp () is traditionally cultivated as a valuable source of fibers and nutrients. Multiple studies also demonstrated antimicrobial, anti-proliferative, phytotoxic and insecticide effects of the essential oil from hemp female inflorescences. On the other side, only a few studies explored the potential pharmacological application of polar extracts from inflorescences. In the present study, we investigated the water extract from inflorescences of industrial hemp Futura 75 variety, from phytochemical and pharmacological point of view. The water extract was assayed for phenolic compound content, radical scavenger/reducing, chelating and anti-tyrosinase effects. Through an ex vivo model of toxicity induced by lipopolysaccharide (LPS) on isolated rat colon and liver, we explored the extract effects on serotonin, dopamine and kynurenine pathways and the production of prostaglandin (PG)E. Anti-proliferative effects were also evaluated against human colon cancer HCT116 cell line. Additionally, antimycotic effects were investigated against Finally, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted in order to predict the putative targets underlying the observed pharmacological and microbiological effects. Futura 75 water extract was able to blunt LPS-induced reduction of serotonin and increase of dopamine and kynurenine turnover, in rat colon. Additionally, the reduction of PGE levels was observed in both colon and liver specimens, as well. The extract inhibited the HCT116 cell viability, the growth of and and the activity of tyrosinase, in vitro, whereas in silico studies highlighting the inhibitions of cyclooxygenase-1 (induced by carvacrol), carbonic anhydrase IX (induced by chlorogenic acid and gallic acid) and lanosterol 14-α-demethylase (induced by rutin) further support the observed pharmacological and antimycotic effects. The present findings suggest female inflorescences from industrial hemp as high quality by-products, thus representing promising sources of nutraceuticals and cosmeceuticals against inflammatory and infectious diseases.
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http://dx.doi.org/10.3390/antiox9050437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278775PMC
May 2020

Qualitative Phytochemical Fingerprint and Network Pharmacology Investigation of Linn. Extracts.

Molecules 2020 Apr 23;25(8). Epub 2020 Apr 23.

Department of Pharmacy, "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.

Linn. (Amaranthaceae), commonly known as the Prickly Chaff flower, is used as herbal medicine in the Ivorian's culture, Africa. Nonetheless, there is currently a paucity of scientific information on from the Ivory Coast. Herein, the antioxidant activity of extracts (methanol, dichloromethane, ethyl acetate and infusion) as well as the enzymatic inhibitory potentials towards key enzymes in human diseases, namely Alzheimer's disease, (cholinesterases: AchE and BChE), type 2 diabetes (α-glucosidase and α-amylase) and hyperpigmentation (tyrosinase) were assessed. The total phenolic (TPC) and flavonoid (TFC) content was determined using colorimetric methods and the individual compounds were characterized using ultra-high performance liquid chromatography coupled with hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-HRMS). Furthermore, a network pharmacology analysis was conducted to predict putative targets of identified phenolic compounds. The highest TPC was observed in the infused extract (28.86 ± 0.12 mg GAE/g), while the dichloromethane extract (38.48 ± 1.48 mg RE/g) showed the highest level of TFC. UHPLC-HRMS analysis has revealed an abundance of fatty acids, flavonoids, phenols and acylquinic acids. Among tested extracts, the infused extract displayed the highest free radical quenching, reducing and metal-chelating ability. The extracts (except infusion) were effective as enzyme inhibitors against AChE, while only methanolic and infused extracts showed noteworthy anti-BChE effects. The methanolic extract showed a remarkable antityrosinase effect (56.24 ± 5.05 mg KAE/g), as well. Modest to moderate inhibitory activity was observed against α-amylase (all extracts) and α-glucosidase (only dichloromethane extract). Finally, the network pharmacology analysis suggested the carbonic anhydrase II enzyme as a putative target for explaining, at least in part, the traditional use of preparations as diuretic and blood clotting agent. Data amassed herein tend to validate the use of in traditional medicine, as well as act as a stepping stone for further studies in the quest for novel phytopharmaceuticals. In this context, it is desirable that this study will contribute to the validation of the traditional uses of this plant in the African herbal medicine, and to the valorization of the whole chain production of , as a local and sustainable botanical resource.
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http://dx.doi.org/10.3390/molecules25081973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221715PMC
April 2020

Synthesis and biological evaluation of new 3(2)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1100-1109

Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.

Novel 3(2)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity and anti-proliferative effects against HCT116 cell lines . lethality test provided LC values >100 µg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.
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http://dx.doi.org/10.1080/14756366.2020.1755670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191905PMC
December 2020

Evaluation of Pharmacological and Phytochemical Profiles (Hook.f.) Brenan Stem Bark Extracts.

Biomolecules 2020 03 28;10(4). Epub 2020 Mar 28.

Department of Pharmacy, "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.

The stem bark (SB) of (PA) has been extensively used in African traditional medicinal systems. However, there is a dearth of scientific information regarding its possible activity in the management of type II diabetes, Alzheimer's disease, and skin hyperpigmentation disorders. This study therefore attempted to elucidate the in vitro inhibitory action of ethyl acetate, methanol, and water extracts of stem bark (PA-SB) on α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. Cell viability, catecholamine, and 3-hydroxykynurenine levels of hypothalamic HypoE22 cells exposed to PA-SB extracts were also investigated. The phytochemical profiles of the extracts were determined by high performance liquid chromatography (HPLC) and antioxidant properties were investigated. Saponin (867.42 mg quillaja equivalent/g) and tannin (33.81 mg catechin equivalent/g) contents were higher in the methanol extract. Multiple dihydroxy-trimethoxy(iso)flavone isomers, loliolide, eriodictyol, naringenin, luteolin, chrysoeriol, apigenin, and liquiritigenin, were characterized from PA-SB extracts using HPLC. The methanol extract of PA-SB showed highest inhibitory activity against acetylcholinesterase (4.88 mg galantamine equivalent (GALAE)/g extract), butyrylcholinesterase (5.37 mg GALAE/g extract), and tyrosinase (154.86 mg kojic acid equivalent/g extract) while α-glucosidase was effectively inhibited by the ethyl acetate extract (15.22 mmol acarbose equivalent/g extract). The methanol extract of PA-SB also showed potent antioxidant properties (493.87, 818.12, 953.07, and 732.19 mg Trolox equivalent/g extract, for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays, respectively). PA-SB extracts exhibited antioxidant activity and promising inhibition against key enzymes related to type II diabetes, Alzheimer's disease, and skin hyperpigmentation disorders. Additionally, all extracts were able to contrast hydrogen peroxide-induced oxidative stress, in HypoE22 cells, thus restoring basal catecholamine and 3-hydroxykinurenine levels, whereas only methanol and water extracts stimulated basal dopamine release. Overall, data from the present study contribute to the biological assessment of that appears to be a promising source of natural compounds with protective and neuromodulatory effects.
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http://dx.doi.org/10.3390/biom10040516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226170PMC
March 2020

Multidirectional Pharma-Toxicological Study on DC. ex Meisn.: An IBD-Focused Investigation.

Antioxidants (Basel) 2020 Feb 18;9(2). Epub 2020 Feb 18.

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Chieti 66100, Italy.

In the present study, we investigated the water extract of DC. ex Meisn. in an experimental model of inflammatory bowel diseases (IBDs). Additionally, a microbiological investigation was carried out to discriminate the efficacy against bacterial and fungal strains involved in IBDs. Finally, an untargeted proteomic analysis was conducted on more than one hundred colon proteins involved in tissue morphology and metabolism. The extract was effective in blunting the production of oxidative stress and inflammation, including serotonin, prostaglandins, cytokines, and transcription factors. Additionally, the extract inhibited the growth of and . The extract was also able to exert a pro-homeostatic effect on the levels of a wide plethora of colon proteins, thus corroborating a protective effect. Conversely, the supraphysiological downregulation of cytoskeletal-related proteins involved in tissue morphology and antimicrobial barrier function suggests a warning in the use of food supplements containing extracts.
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http://dx.doi.org/10.3390/antiox9020168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070412PMC
February 2020

Biopotential of Fresen Stem Bark Extracts: UHPLC Profiles, Antioxidant, Enzyme Inhibitory, and Antiproliferative Propensities.

Antioxidants (Basel) 2020 Feb 17;9(2). Epub 2020 Feb 17.

Department of Pharmacy, "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.

In this study, ethyl acetate, methanol, and water extracts of (Melianthaceae) stem bark were screened for enzyme inhibitory and antioxidant properties. The water extract possessed the highest concentration of phenols (230.83 mg gallic acid equivalent/g extract), while the methanol extract was rich in flavonoids (75.82 mg rutin equivalent/g extract), and the ethyl acetate extract possessed the highest amount of saponins (97.37 mg quillaja equivalent/g). The aim of this study was to investigate the antiproliferative effects against the human colon cancer HCT116 cell line challenged with serotonin (5-HT) as a stimulating-proliferation factor. The level of HCT116 cell-deriving pool of kynurenic acid (KA) was also assessed. The UHPLC results confirmed the presence of 58, 68, and 63 compounds in the ethyl acetate, methanol, and water extracts, respectively. Mangiferin, vitexin and its isomer isovitexin were tentatively identified in all extracts and KA ( 190.05042 [M-H]) was also tentatively identified in the methanol and water extracts. The methanol extract (1464.08 mg Trolox equivalent [TE]/g extract) showed the highest activity in the CUPRAC assay, whereas the water extract (1063.70 mg TE/g extract) showed the highest activity with the FRAP technique. The ethyl acetate extract was the most active acetylcholinesterase (4.43 mg galantamine equivalent/g extract) and α-glucosidase (mmol acarbose equivalent /g extract) inhibitor. The water extract was able to inhibit 5-HT-stimulated viability of HCT116 cells, and blunt 5-HT-induced reduction of cell-deriving KA. The scientific data generated in this study provide baseline data regarding the biological properties of stem bark, highlighting its potential use for the development of new pharmaceutic and cosmetic agents.
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http://dx.doi.org/10.3390/antiox9020163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094211PMC
February 2020

Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf.

Antioxidants (Basel) 2020 Feb 2;9(2). Epub 2020 Feb 2.

Department of Pharmacy, "G. d'Annunzio" University Chieti-Pescara, 66100 Chieti, Italy.

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 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 , 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 methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses.
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http://dx.doi.org/10.3390/antiox9020128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070247PMC
February 2020

Antinflammatory, antioxidant, and behavioral effects induced by administration of growth hormone-releasing hormone analogs in mice.

Sci Rep 2020 01 20;10(1):732. Epub 2020 Jan 20.

Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.

Growth hormone-releasing hormone (GHRH) antagonist MIA-690 and GHRH agonist MR-409, previously synthesized and developed by us have demonstrated potent antitumor effects. However, little is known about the effects of these analogs on brain functions. We investigated the potential antinflammatory and antioxidant effects of GHRH antagonist MIA-690 and GHRH agonist MR-409, on isolated mouse prefrontal cortex specimens treated with lipopolysaccharide (LPS). Additionally, we studied their effects on emotional behavior after chronic in vivo treatment. Ex vivo, MIA-690 and MR-409 inhibited LPS-induced inflammatory and pro-oxidative markers. In vivo, both MIA-690 and MR-409 induced anxiolytic and antidepressant-like effects, increased norepinephrine and serotonin levels and decreased nuclear factor-kB, tumor necrosis factor-α and interleukin-6 gene expression in prefrontal cortex. Increased nuclear factor erythroid 2-related factor 2 expression was also found in mice treated with MIA-690 and MR-409. MIA-690 showed higher efficacy in inhibiting all tested inflammatory and oxidative markers. In addition, MR-409 induced a down regulation of the gene and protein expression of pituitary-type GHRH-receptor in prefrontal cortex of mice after 4 weeks of treatment at 5 µg/day. In conclusion, our results demonstrate anxiolytic and antidepressant-like effects of GHRH analogs that could involve modulatory effects on monoaminergic signaling, inflammatory and oxidative status.
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http://dx.doi.org/10.1038/s41598-019-57292-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971229PMC
January 2020

Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus.

Antioxidants (Basel) 2020 Jan 13;9(1). Epub 2020 Jan 13.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

Background: Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from , 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.

Methods: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined.

Results: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis.

Conclusion: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.
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http://dx.doi.org/10.3390/antiox9010071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022242PMC
January 2020

Growth hormone-releasing hormone (GHRH) deficiency promotes inflammation-associated carcinogenesis.

Pharmacol Res 2020 02 23;152:104614. Epub 2019 Dec 23.

Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.

The somatotropic axis, in addition to its well-known metabolic and endocrine effects, plays a pivotal role in modulation of inflammation. Moreover, growth hormone (GH)-releasing hormone (GHRH) has been involved in the development of various human tumors. In this work we aimed to investigate the consequences of GHRH deficiency on the development of inflammation-associated colon carcinogenesis in a mouse model of isolated GH deficiency due to generalized ablation of the GHRH gene [GHRH knock out (GHRHKO)]. Homozygous GHRHKO (-/-) male mice and wild type (C57/BL6, +/+) male mice as control group, were used. After azoxymetane (AOM)/dextran sodium sulfate (DSS) treatment -/- mice displayed higher Disease Activity Index (DAI) score, and more marked weight loss compared to +/+ animals. Additionally, -/- mice showed a significant increase in total tumors, in particular of large size predominantly localized in distal colon. In colonic tissue of AOM/DSS-treated -/- mice we found the presence of invasive adenocarcinomas, dysplasia and colitis with mucosal ulceration. Conversely, AOM/DSS-treated +/+ mice showed only presence of adenomas, without invasion of sub-mucosa. Treatment with AOM/DSS significantly increased prostaglandin (PG)E and 8-iso-PGF levels along with cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-kB) and inducible nitric oxide synthase (iNOS) gene expression, in colon specimens. The degree of increase of all these parameters was more markedly in -/- than +/+ mice. In conclusion, generalized GHRH ablation increases colon carcinogenesis responsiveness in male mice. Whether this results from lack of GH or GHRH remains to be established.
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http://dx.doi.org/10.1016/j.phrs.2019.104614DOI Listing
February 2020