Publications by authors named "Luigi Brunetti"

147 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

Impact of body mass index on survival and serious adverse events in advanced non-small cell lung cancer treated with bevacizumab: a meta-analysis of randomized clinical trials.

Curr Med Res Opin 2021 Mar 24:1-7. Epub 2021 Mar 24.

Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, The State University of New Jersey, Rutgers, NJ, USA.

Purpose: Lung cancer accounts for 28% of all cancer deaths, more deaths than any other cancer in the United States. The influence of body composition has been evaluated in several studies, specifically, the influence of obesity on lung cancer survival. Outcomes have been mixed, with some studies demonstrating a paradoxical beneficial effect in early lung cancer where survival is improved in obese patients. The study aim was to evaluate the impact of obesity on overall survival (OS), progression free survival (PFS), and occurrence of serious adverse events (SAE) in clinical trials evaluating bevacizumab for advanced non-small cell lung cancer (NSCLC).

Methods: We performed a post hoc analysis combining available individual level data from bevacizumab randomized clinical trials available through the Clinical Study Data Request database. The primary outcome measured in our analysis was the influence of bevacizumab on OS stratified by body mass index (BMI). In addition to OS, both PFS and the occurrence of SAE requiring therapy interruption were evaluated. All endpoints were evaluated in patients who were obese (BMI ≥30.0 kg/m) compared with non-obese (BMI <30.0 kg/m). As a sensitivity analysis, endpoints were also evaluated in patients who were overweight (BMI ≥25.0 kg/m) compared with non-overweight (BMI <25.0 kg/m). In addition to analysis of each individual study, a meta-analysis was performed in order to calculate pooled hazard ratios (HR). Hazard ratios for both OS and PFS were calculated using multivariable Cox proportional hazards models. Odds ratios for SAE were calculated using multivariable logistic regression. The validity of the regression models was tested using a log-log plot and overall fit using the goodness of fit test.

Results: After adjusting for covariates using a Cox proportional hazards model and combining the resulting adjusted hazard ratios using meta-analysis, there was no significant difference between obese and non-obese groups for OS or PFS. In addition, when treatment discontinuation due to an adverse event was assessed, none of the trials showed a significant difference between the obese and non-obese groups.

Conclusion: In this analysis of clinical trial data, obesity was not associated with worse survival versus non-obese individuals in advanced NSCLC. In addition, serious adverse events were similar between patients with and without obesity.
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http://dx.doi.org/10.1080/03007995.2021.1900091DOI Listing
March 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

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

Risk Factors and Outcomes of Hospitalized Patients with Severe COVID-19 and Secondary Bloodstream Infections: A Multicenter, Case-Control Study.

Clin Infect Dis 2020 Nov 20. Epub 2020 Nov 20.

Department of Medicine, Division of Allergy/Immunology and Infectious Disease, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.

Background: Coronavirus disease 2019 (COVID-19) has become a global pandemic. Clinical characteristics regarding secondary infections in patients with COVID-19 have been reported but detailed microbiology, risk factors and outcomes of secondary bloodstream infections (sBSI) in patients with severe COVID-19 have not been well described.

Methods: We performed a multicenter, case-control study including all hospitalized patients diagnosed with severe COVID-19 and blood cultures drawn from March 1, 2020 to May 7, 2020 at three academic medical centers in New Jersey, USA. Data collection included demographics, clinical and microbiologic variables, and patient outcomes. Risk factors and outcomes were compared between cases (sBSI) and controls (no sBSI).

Results: A total of 375 hospitalized patients were included. There were 128 sBSIs during the hospitalization. For the first set of positive blood cultures, 117 (91.4%) were bacterial and 7 (5.5%) were fungal. Those with sBSI were more likely to have altered mental status, lower mean percent oxygen saturation on room air, have septic shock and be admitted to the intensive care unit compared to the controls. In-hospital mortality was higher in those with a sBSI versus controls (53.1% vs 32.8%, p=0.0001).

Conclusions: We observed hospitalized adult patients with severe COVID-19 and sBSI had a more severe initial presentation, prolonged hospital course, and worse clinical outcomes. To maintain antimicrobial stewardship principles, further prospective studies are necessary to better characterize risk factors and prediction modeling to better understand when to suspect and empirically treat for sBSI in severe COVID-19.
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http://dx.doi.org/10.1093/cid/ciaa1748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717183PMC
November 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

Impact of Hydroxychloroquine on Mortality in Hospitalized Patients with COVID-19: Systematic Review and Meta-Analysis.

Pharmacy (Basel) 2020 Nov 5;8(4). Epub 2020 Nov 5.

Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused significant health and economic havoc around the globe. One of the early agents targeted for repurposing to treat and prevent COVID-19 was hydroxychloroquine (HCQ). In this systematic review and meta-analysis, HCQ is evaluated for its potential role in decreasing mortality in hospitalized patients with COVID-19. We searched PubMed, Web of Science, and medRxiv databases using combinations of the terms "COVID-19", "SARS-CoV-2", "coronavirus", "hydroxychloroquine", and "mortality". Articles were selected for further review based on the content of their abstracts. Studies were excluded if they were of poor methodological quality, were not based in the inpatient setting, or did not have available data to assess the primary outcome of death between patients treated with HCQ versus standard of care. Once the final dataset was compiled, a meta-analysis using the random-effects model was performed. Our search identified 14 studies involving 24,780 patients of whom 12,707 patients were on HCQ alone or in combination with other adjuvant therapies. HCQ alone or in combination with other drugs did not significantly decrease mortality in hospitalized patients with COVID-19 (odds ratio [OR], 0.95; 95% CI, 0.72-1.26; = 0.732; = 91.05). Similar findings were observed in all subgroup analyses. HCQ did not significantly impact mortality in hospitalized patients with COVID-19. Additional well-designed studies are essential due to the heterogeneity in available studies.
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http://dx.doi.org/10.3390/pharmacy8040208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711623PMC
November 2020

Impact of tocilizumab administration on mortality in severe COVID-19.

Sci Rep 2020 11 5;10(1):19131. Epub 2020 Nov 5.

Robert Wood Johnson University Hospital Somerset, 110 Rehill Avenue, Somerville, NJ, 08876, USA.

The novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to an aberrant inflammatory response or cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. A total of 274 patients meeting inclusion and exclusion criteria were identified and 132 patients were included in the matched dataset (tocilizumab = 66; no tocilizumab = 66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group (odds ratio, 1.0; 95% confidence interval, 0.465 - 2.151; p = 1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.
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http://dx.doi.org/10.1038/s41598-020-76187-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645706PMC
November 2020

Assessment of burnout among postgraduate pharmacy residents: A pilot study.

Curr Pharm Teach Learn 2021 Jan 27;13(1):42-48. Epub 2020 Aug 27.

Department of Pharmacy Practice and Administration, Rutgers University - Ernest Mario School of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, United States. Electronic address:

Introduction: Health professional burnout has become a topic of growing interest given increased focus on mental health and well-being. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) has been commonly utilized to quantify health professional burnout, but the literature does not report burnout among pharmacy residents. The objective of this study was to quantify burnout status of pharmacy residents and to correlate burnout to professional conduct and career outlook.

Methods: Pharmacy residents completed an electronic, anonymous survey at a teaching and learning certificate meeting date. Burnout status was measured by a high score on either the emotional exhaustion or depersonalization subscales of the MBI-HSS tool.

Results: Forty-three of 58 surveys were completed (response rate 74.1%). The burnout rate among residents was 74.4%. No significant differences were seen in baseline demographics, except burned out subjects were more likely to report a "single" relationship status. Activities such as using sick days when not ill, falling asleep at work, overlooking others' breaches of institutional guidelines, and failure to follow-up in a timely fashion were significantly correlated to burnout status with moderate correlation coefficients.

Conclusions: The point prevalence of burnout among pharmacy residents is similar to that documented for practicing pharmacists and physicians. Expansion to a larger, more diverse sample size would provide additional power to differentiate independent risk factors for burnout and to better quantify associations to professional conduct among pharmacy residents.
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http://dx.doi.org/10.1016/j.cptl.2020.08.008DOI Listing
January 2021

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

Colchicine to Weather the Cytokine Storm in Hospitalized Patients with COVID-19.

J Clin Med 2020 Sep 14;9(9). Epub 2020 Sep 14.

Division of Rheumatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

The repurposing of colchicine for the treatment of COVID-19 was suggested based in its immunomodulatory, anti-inflammatory, and anti-viral properties. We performed a single-center propensity score matched cohort study, including all consecutive COVID-19 patients admitted to a community hospital between 1 March 2020 and 30 May 2020. Patients were stratified according to the receipt of colchicine. The primary endpoint was defined as in-hospital death within 28-days follow-up. Secondary endpoints included favorable change in the Ordinal Scale for Clinical Improvement on days 14 and 28 versus baseline, proportion of patients not requiring supplemental oxygen on days 14 and 28, and proportion of patients discharged by day 28. In total data for 303 PCR positive COVID-19 patients were extracted and 66 patients were included in the 1:1 matched cohort study. At the end of the 28 day follow-up, patients receiving colchicine were approximately five times more likely to be discharged (odds ratio, 5.0; 95% confidence interval, 1.25-20.1; = 0.023) and when comparing mortality, there were 3 deaths (9.1%) in patients receiving colchicine versus 11 deaths (33.3%) in the groups receiving standard of care (odds ratio, 0.20; 95% confidence interval, 0.05-0.80; = 0.023). These observations warrant further investigation in large controlled clinical trials.
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http://dx.doi.org/10.3390/jcm9092961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565543PMC
September 2020

Colchicine in COVID-19: an Old Drug, New Use.

Curr Pharmacol Rep 2020 Jul 18:1-9. Epub 2020 Jul 18.

Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ USA.

Purpose Of Review: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is a pandemic causing havoc globally. Currently, there are no Food and Drug Administration (FDA)-approved drugs to treat COVID-19. In the absence of effective treatment, off-label drug use, in lieu of evidence from published randomized, double-blind, placebo-controlled clinical trials, is common in COVID-19. Although it is vital to treat affected patients with antiviral drugs, there is a knowledge gap regarding the use of anti-inflammatory drugs in these patients.

Recent Findings: Colchicine trials to combat inflammation in COVID-19 patients have not received much attention. We await the results of ongoing colchicine randomized controlled trials in COVID-19, evaluating colchicine's efficacy in treating COVID-19.

Summary: This review gives a spotlight on colchicine's anti-inflammatory and antiviral properties and why colchicine may help fight COVID-19 This review summarizes colchicine's mechanism of action via the tubulin-colchicine complex. Furthermore, it discussed how colchicine interferes with several inflammatory pathways, including inhibition of neutrophil chemotaxis, adhesion, and mobilization; disruption of superoxide production, inflammasome inhibition, and tumor necrosis factor reduction; and its possible antiviral properties. In addition, colchicine dosing and pharmacokinetics, as well as drug interactions and how they relate to ongoing, colchicine in COVID-19 clinical trials, are examined.
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http://dx.doi.org/10.1007/s40495-020-00225-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367785PMC
July 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

Hot Topic Commentary on COVID-19.

Curr Pharmacol Rep 2020 May 11:1-3. Epub 2020 May 11.

3Department of Pharmacy Practice, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 USA.

The recent pandemic outbreak of COVID-19 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) worldwide caught the health care systems in every country around the world by storm and without a proper defense mechanism to cope and control such a pandemic. In this special Theme issue, we would like to discuss the latest treatment modalities available around the world in tackling this dreadful disease.
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http://dx.doi.org/10.1007/s40495-020-00215-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212506PMC
May 2020

An Update on Current Therapeutic Drugs Treating COVID-19.

Curr Pharmacol Rep 2020 May 11:1-15. Epub 2020 May 11.

1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 USA.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2.
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http://dx.doi.org/10.1007/s40495-020-00216-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211915PMC
May 2020

Acid suppression medications during hospitalization as a risk factor for recurrence of Clostridioides difficile infection: systematic review and meta-analysis.

Clin Infect Dis 2020 May 9. Epub 2020 May 9.

Department of Pharmacy Practice and Administration; Ernest Mario School of Pharmacy; Rutgers, The State University of New Jersey; Piscataway, NJ, USA.

Background: Studies have had conflicting results regarding the influence of acid suppression medications (ASM) during hospitalization on the recurrence of Clostridioides difficile infection (CDI).

Methods: A systematic review and meta-analysis investigating the association between recurrent CDI and ASM use in inpatients was performed. Relevant literature was identified using Medline, Google Scholar, and Web of Science. All human studies were considered regardless of when they were published. Case-control studies, cohort studies, and clinical trials were included if they contained the necessary information to calculate appropriate statistics related to the objective of this study. Review articles, meta-analyses, and commentaries were excluded; however, their references were searched to identify any studies missed. The random-effects model was selected since significant heterogeneity in study design was identified. To evaluate the sensitivity of the analysis various subgroup analyses were performed.

Results: Our search identified 9 studies involving 5668 patients of whom 1003 (17.7%) developed recurrent CDI. Patients on ASM were 64% more likely to develop recurrent CDI compared to patients not on ASM (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.13 - 2.38; p-value = 0.009; I2=79.54%). Proton pump inhibitor use was associated with an 84% increased risk of recurrent CDI versus no ASM (OR, 1.84; 95% CI, 1.18 - 2.85; p-value=0.007; I2=83.4%).

Conclusions: ASM use during hospitalization was associated with a 64% increase in recurrent CDI. The association was greater with PPI use. Due to significant heterogeneity in the analyses, additional studies are essential to further elucidate iatrogenic effect of ASM. Unnecessary PPI use should always be discontinued.
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http://dx.doi.org/10.1093/cid/ciaa545DOI Listing
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

The risk of vancomycin toxicity in patients with liver impairment.

Ann Clin Microbiol Antimicrob 2020 Mar 31;19(1):13. Epub 2020 Mar 31.

Department of Pharmacy Administration, Chung-Ang University College of Pharmacy, Seoul, South Korea.

Background: The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined.

Methods: A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child-Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables.

Results: A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063).

Conclusions: MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.
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http://dx.doi.org/10.1186/s12941-020-00354-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110653PMC
March 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