giancarlo aldini
@unimi.it
Deprtment of Pharmaceutical Sciences
University of Milan
RESEARCH INTERESTS
Pharmaceutical and biomedical analysis, drug discovery, herbal drugs
Scopus Publications
Scopus Publications
Saeede Saadati, Robel Hussen Kabthymer, Giancarlo Aldini, Aya Mousa, Jack Feehan, and Barbora de Courten
Oxford University Press (OUP)
Abstract Context Carnosine and histidine-containing dipeptides (HCDs) are suggested to have anti-inflammatory and antioxidative benefits, but their effects on circulating adipokines and inflammatory and oxidative stress biomarkers remain unclear. Objectives The aim of the present systematic review and meta-analysis was to determine the impact of HCD supplementation on inflammatory and oxidative stress biomarkers. Data Sources A systematic search was performed on Medline via Ovid, Scopus, Embase, ISI Web of Science, and the Cochrane Library databases from inception to 25 January 2023. Data Extraction Using relevant key words, trials investigating the effects of carnosine/HCD supplementation on markers of inflammation and oxidative stress, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) were identified. Meta-analyses were conducted using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Data Analysis A total of 9 trials comprising 350 participants were included in the present meta-analysis. Carnosine/HCD supplementation led to a significant reduction in CRP (WMD: –0.97 mg/L; 95% CI: –1.59, –0.36), TNF-α (WMD: –3.60 pg/mL; 95% CI: –7.03, –0.18), and MDA (WMD: –0.34 μmol/L; 95% CI: –0.56, –0.12) and an elevation in CAT (WMD: 4.48 U/mL; 95% CI: 2.43, 6.53) compared with placebo. In contrast, carnosine/HCD supplementation had no effect on IL-6, adiponectin, GSH, SOD, and TAC levels. Conclusion Carnosine/HCD supplementation may reduce inflammatory and oxidative stress biomarkers, and potentially modulate the cardiometabolic risks associated with chronic low-grade inflammation and lipid peroxidation. Systematic Review Registration PROSPERO registration no. CRD42017075354.
Charlotte Wetzel, Nadia Gallenstein, Verena Peters, Thomas Fleming, Iva Marinovic, Alea Bodenschatz, Zhiwei Du, Katharina Küper, Clelia Dallanoce, Giancarlo Aldini,et al.
Springer Science and Business Media LLC
AbstractIntegrity of epithelial and endothelial cell barriers is of critical importance for health, barrier disruption is a hallmark of numerous diseases, of which many are driven by carbonyl stressors such as methylglyoxal (MG). Carnosine and anserine exert some MG-quenching activity, but the impact of these and of other histidine containing dipeptides on cell barrier integrity has not been explored in detail. In human proximal tubular (HK-2) and umbilical vein endothelial (HUVEC) cells, exposure to 200 µM MG decreased transepithelial resistance (TER), i.e. increased ionic permeability and permeability for 4-, 10- and 70-kDa dextran, membrane zonula occludens (ZO-1) abundance was reduced, methylglyoxal 5-hydro-5-methylimidazolones (MG-H1) formation was increased. Carnosine, balenine (ß-ala-1methyl-histidine) and anserine (ß-ala-3-methyl-histidine) ameliorated MG-induced reduction of TER in both cell types. Incubation with histidine, 1-/3-methylhistidine, but not with ß-alanine alone, restored TER, although to a lower extent than the corresponding dipeptides. Carnosine and anserine normalized transport and membrane ZO-1 abundance. Aminoguanidine, a well-described MG-quencher, did not mitigate MG-induced loss of TER. Our results show that the effects of the dipeptides on epithelial and endothelial resistance and junction function depend on the methylation status of histidine and are not exclusively explained by their quenching activity.
Massimiliano Tucci, Cristian Del Bo’, Daniela Martini, Simone Perna, Mirko Marino, Marco Rendine, Claudio Gardana, Alberto Battezzati, Alessandro Leone, Simona Bertoli,et al.
Elsevier BV
Michele Manoni, Alessandra Altomare, Simona Nonnis, Giulio Ferrario, Sharon Mazzoleni, Marco Tretola, Giuseppe Bee, Gabriella Tedeschi, Giancarlo Aldini, and Luciano Pinotti
Springer Science and Business Media LLC
AbstractReplacing cereals with food leftovers could reduce feed-food competition and keep nutrients and energy in the food chain. Former food products (FFPs) are industrial food leftovers no more intended for human but still suitable as alternative and sustainable feedstuffs for monogastric. In this study, omics approaches were applied to evaluate the impact of dietary FFPs on pig liver proteome and plasma peptidome. Thirty-six Swiss Large White male castrated pigs were randomly assigned to three dietary treatments [control (CTR), 30% CTR replaced with salty FFP (SA), 30% CTR replaced with sugary FFP (SU)] from the start of the growing phase (22.4 ± 1.7 kg) until slaughtering (110 ± 3 kg). The low number of differentially regulated proteins in each comparison matrix (SA/SU vs. CTR) and the lack of metabolic interaction indicated a marginal impact on hepatic lipid metabolism. The plasma peptidomics investigation showed low variability between the peptidome of the three dietary groups and identified three possible bioactive peptides in the SA group associated with anti-hypertension and vascular homeostasis regulation. To conclude, the limited modulation of liver proteome and plasma peptidome by the SA and SU diets strenghtened the idea of reusing FFPs as feed ingredients to make pig production more sustainable.
Saeede Saadati, Maximilian de Courten, Cyril Deceneux, Magdalena Plebanski, David Scott, Jakub Mesinovic, Paul Jansons, Giancarlo Aldini, James Cameron, Jack Feehan,et al.
MDPI AG
Background/Objectives: In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D). Methods: Out of 88 participants who were recruited, 49 adults with prediabetes or well-controlled T2D (HbA1c: 6.6 ± 0.7% [mean ± SD]) who were treated with diet and/or metformin were eligible for inclusion. Participants were randomised to receive 2 g/day of carnosine or a matching placebo for 14 weeks. We measured serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), adiponectin, leptin, adipsin, serpin, and resistin levels at baseline and after 14 weeks. The trial was registered at clinicaltrials.gov (NCT02917928). Results: Forty-one participants (M = 29/F = 12) aged 53 (42.6, 59.3) years [median (IQR)] completed the trial. After 14 weeks of supplementation, changes in pro- and anti-inflammatory cytokine and adipokine levels did not differ between the carnosine and placebo groups (p > 0.05 for all). The results remained unchanged after adjustment for confounders including age, sex, and anthropometric measures (e.g., body fat percentage and visceral adipose tissue). Conclusions: In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D.
Alfonsina D’Amato, Alessandra Altomare, Ettore Gilardoni, Giovanna Baron, Marina Carini, Elsa Melloni, Gloria Padoani, Silvia Vailati, Giovanni Caponetti, and Giancarlo Aldini
Elsevier BV
Gilda Aiello, Davide Tosi, Giancarlo Aldini, Marina Carini, and Alfonsina D’Amato
MDPI AG
Lipids are emerging as important potential targets for the early diagnosis and prognosis of several inflammatory diseases. Studying the lipid profiles is important for understanding cellular events such as low-grade inflammation, a condition common to many human diseases, including cancer, neurodegenerative diseases, diabetes, and obesity. This work aimed to explore lipid signatures in an inflammation cellular model using an advanced bioanalytical approach complemented by Machine Learning techniques. Analyses based on the high-resolution mass spectrometry of extracted lipids in TNF-α inflamed cells (R3/1 NF-κB reporter cells) versus lipids in control cells resulted in 469 quantified lipids, of which 20% were phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), 10% were sphingomyelins (SMs), 6% were phosphatidylinositols (PIs), 7% were ceramides (Cer), 6% were phosphatidylglycerols (PGs), and 5% were phosphatidylserines (PSs). TNF-α induced a significant alteration compared to the control, with a fold change higher than 1.5; of the 88 lipids, 71 were upregulated and 17 were downregulated, impacting various pathways as revealed by network analyses. To validate the inflammation model, the TNF-α induced cells were treated with polyphenols from thinned young apples (TAPs), which are known to have anti-inflammatory properties. The dysregulation of ceramides (Cer(d18:1/23:0), Cer(d18:1/23:0), and Cer(d18:1/22:0)) observed in TNF-α inflamed cells was completely reverted after TAP treatment. Network analyses showed the alteration of arachidonic acid and TNF signaling, which were modulated by polyphenols from thinned young apples. The results highlighted the potentiality of the inflammatory model and the bioanalytical approach to describe lipid profiles in complex biological matrices and different states. In addition, the quantified lipids were interpreted by an Artificial Intelligence approach to identify relevant signatures and clusters of lipids that can impact cellular states. Lastly, this study underlines both the potential applications of lipidomics combined with Machine Learning and how to build and validate Machine Learning models to predict inflammation based on lipid-related pattern signatures.
Alexandra Ioana Corfu, Nuno Santarem, Sara Luelmo, Gaia Mazza, Alessandro Greco, Alessandra Altomare, Giulio Ferrario, Giulia Nasta, Oliver Keminer, Giancarlo Aldini,et al.
American Chemical Society (ACS)
Vector-borne parasitic diseases (VBPDs) pose a significant threat to public health on a global scale. Collectively, Human African Trypanosomiasis (HAT), Leishmaniasis, and Malaria threaten millions of people, particularly in developing countries. Climate change might alter the transmission and spread of VBPDs, leading to a global burden of these diseases. Thus, novel agents are urgently needed to expand therapeutic options and limit the spread of drug-resistant parasites. Herein, we report the development of broad-spectrum antiparasitic agents by screening a known library of antileishmanial and antimalarial compounds toward Trypanosoma brucei (T. brucei) and identifying a 1,3,4-oxadiazole derivative (19) as anti-T. brucei hit with predicted blood-brain barrier permeability. Subsequently, extensive structure-activity-relationship studies around the lipophilic tail of 19 led to a potent antitrypanosomal and antimalarial compound (27), with moderate potency also toward Leishmania infantum (L. infantum) and Leishmania tropica. In addition, we discovered a pan-active antiparasitic molecule (24), showing low-micromolar IC50s toward T. brucei and Leishmania spp. promastigotes and amastigotes, and nanomolar IC50 against Plasmodium falciparum, together with high selectivity for the parasites over mammalian cells (THP-1). Early ADME-toxicity assays were used to assess the safety profile of the compounds. Overall, we characterized 24 and 27, bearing the 1,3,4-oxadiazole privileged scaffold, as broad-spectrum low-toxicity agents for the treatment of VBPDs. An alkyne-substituted chemical probe (30) was synthesized and will be utilized in proteomics experiments aimed at deconvoluting the mechanism of action in the T. brucei parasite.
Alessandra Altomare, Giovanna Baron, Giulia Cambiaghi, Giulio Ferrario, Beatrice Zoanni, Larissa Della Vedova, Giulio Maria Fumagalli, Sarah D’Alessandro, Silvia Parapini, Serena Vittorio,et al.
MDPI AG
Background: The viral main protease (Mpro) of SARS-CoV-2 has been recently proposed as a key target to inhibit virus replication in the host. Therefore, molecules that can bind the catalytic site of Mpro could be considered as potential drug candidates in the treatment of SARS-CoV-2 infections. Here we proposed the application of a state-of-the-art analytical platform which combines metabolomics and protein structure analysis to fish-out potential active compounds deriving from a natural matrix, i.e., a blueberry extract. Methods: The experiments focus on finding MS covalent inhibitors of Mpro that contain in their structure a catechol/pyrogallol moiety capable of binding to the nucleophilic amino acids of the enzyme’s catalytic site. Results: Among the potential candidates identified, the delphinidin-3-glucoside showed the most promising results. Its antiviral activity has been confirmed in vitro on Vero E6 cells infected with SARS-CoV-2, showing a dose-dependent inhibitory effect almost comparable to the known Mpro inhibitor baicalin. The interaction of delphinidin-3-glucoside with the Mpro pocket observed was also evaluated by computational studies. Conclusions: The HRMS analytical platform described proved to be effective in identifying compounds that covalently bind Mpro and are active in the inhibition of SARS-CoV-2 replication, such as delphinidin-3-glucoside.
Clarissa Caroli, Giovanna Baron, Giorgio Cappellucci, Virginia Brighenti, Larissa Della Vedova, Francesca Fraulini, Simonetta Oliaro-Bosso, Andrea Alessandrini, Alfonso Zambon, Gigliola Lusvardi,et al.
Elsevier BV
Juliana Silva Siqueira, Jessica Leite Garcia, Artur Junio Togneri Ferron, Fernando Moreto, Luis Eduardo Sormani, Mariane Rovero Costa, Thiago Luiz Novaga Palacio, Gisele Alborghetti Nai, Giancarlo Aldini, Fabiane Valentini Francisqueti-Ferron,et al.
Elsevier BV
Federica Blua, Chiara Monge, Simone Gastaldi, Nausicaa Clemente, Stefania Pizzimenti, Loretta Lazzarato, Rebecca Senetta, Serena Vittorio, Casimiro Luca Gigliotti, Elena Boggio,et al.
Elsevier BV
Núbia Alves Grandini, Mariane Róvero Costa, Cristina Schmitt Gregolin, Juliana Silva Siqueira, Taynara Aparecida Vieira, Artur Junio Togneri Ferron, Fabiane Valentini Francisqueti-Ferron, Guilherme Ribeiro Romualdo, Ana Lúcia dos Anjos Ferreira, Giancarlo Aldini,et al.
Elsevier BV
Angelica Artasensi, Sarah Mazzotta, Giovanna Baron, Giancarlo Aldini, and Laura Fumagalli
Royal Society of Chemistry (RSC)
Deuterated proanthocyanidin metabolite 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone has been successfully produced.
Juliana Silva Siqueira, Erika Tiemi Nakandakare-Maia, Taynara Aparecida Vieira, Thiago Luiz Novaga Palacio, Matheus Antônio Filiol Belin, Giovanna Baron, Silmeia Garcia Zanati Bazan, Artur Junio Togneri Ferron, Giancarlo Aldini, Fabiane Valentini Francisqueti-Ferron,et al.
Elsevier BV
Fernando Moreto, Jéssica Leite Garcia, Ana Lúcia dos Anjos Ferreira, Silvia Radrezza, Mariane Róvero Costa, Guilherme Ribeiro Romualdo, Nubia Alves Grandini, Giancarlo Aldini, Camila Renata Correa, and Alfonsina D'Amato
Wiley
AbstractThe nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD‐rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label‐free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up‐ and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR‐treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.
G. Baron, A. Altomare, L. Della Vedova, F. Gado, O. Quagliano, S. Casati, N. Tosi, L. Bresciani, D. Del Rio, G. Roda,et al.
Elsevier BV
Larissa Della Vedova, Islam Husain, Yan‐Hong Wang, Hari Babu Kothapalli, Francesca Gado, Giovanna Baron, Simone Manzi, Paolo Morazzoni, Giancarlo Aldini, and Ikhals A. Khan
Wiley
Abstract5‐(3′,4′‐Dihydroxyphenyl)‐γ‐valerolactone (VL) is a bioactive metabolite resulting from the gut microbial metabolism of proanthocyanidins and flavonoids, known for its health‐promoting effects, including antidiabetic and anti‐inflammatory activities. Although VL has been observed in different in vivo studies, its pre‐absorption, distribution, metabolism, excretion, toxicity (ADMET) properties have rarely been investigated. This study aims to address this gap by evaluating the pre‐ADMET properties of VL for the first time. Also, the understanding of these properties is significant for correlating the encountered activities to this metabolite. In vitro absorption studies revealed that VL is rapidly metabolized and absorbed as its sulfate phase II conjugate (valerolactone sulfate), which enters systemic circulation and mildly activates the Breast Cancer Resistance Protein efflux transporter. In human S9 liver fraction, a mixture of liver enzymes used to simulate in vivo liver metabolism, VL is metabolized into glucuronic phase II conjugates (valerolactone glucuronide 1 [VLG1] and 2 [VLG2]) with a half‐life of 8.72 min and an 80% conversion rate. In human liver microsomes, VL is metabolized at a slower rate (half‐life of 23.08 min), suggesting that oxidative metabolism is secondary. Additionally, VL did not activate the pregnane X receptor or inhibit Cytochrome P3A4 (CYP3A4) and Cytochrome P1A2 (CYP1A2) enzymes, indicating no risk of herb–drug interactions with coadministered prescription drugs.
Benedetta Bassetti, Roberto Ballini, Pietro Allegrini, Giancarlo Aldini, and Alessandro Palmieri
Wiley
AbstractHerein we report a new practical and efficient multistep syntheses of 1”‐ and 2”‐hydroxycannabidiol metabolites. Both products and intermediates were fully characterized, and the target metabolites were produced in good overall yields.
Carlo Savini, Elena Tenti, Elisa Mikus, Sonia Eligini, Marco Munno, Anna Gaspardo, Erica Gianazza, Arianna Greco, Stefania Ghilardi, Giancarlo Aldini,et al.
MDPI AG
Recent evidence indicates that reactive oxygen species play an important causative role in the onset and progression of valvular diseases. Here, we analyzed the oxidative modifications of albumin (HSA) occurring on Cysteine 34 and the antioxidant capacity of the serum in 44 patients with severe aortic stenosis (36 patients underwent aortic valve replacement and 8 underwent a second aortic valve substitution due to a degenerated bioprosthetic valve), and in 10 healthy donors (controls). Before surgical intervention, patients showed an increase in the oxidized form of albumin (HSA-Cys), a decrease in the native reduced form (HSA-SH), and a significant reduction in serum free sulfhydryl groups and in the total serum antioxidant activity. Patients undergoing a second valve replacement showed levels of HSA-Cys, free sulfhydryl groups, and total antioxidant activity similar to those of controls. In vitro incubation of whole blood with aspirin (ASA) significantly increased the free sulfhydryl groups, suggesting that the in vivo treatment with ASA may contribute to reducing oxidative stress. We also found that N-acetylcysteine and its amide derivative were able to regenerate HSA-SH. In conclusion, the systemic oxidative stress reflected by high levels of HSA-Cys is increased in patients with aortic valve stenosis. Thiol–disulfide breaking agents regenerate HSA-SH, thus paving the way to the use these compounds to mitigate the oxidative stress occurring in the disease.
Rogil Jose de Almeida Torres, Fernando Moreto, Andrea Luchini, Rogerio Joao de Almeida Torres, Sofia Pimentel Longo, Ricardo Aurino Pinho, Seigo Nagashima, Lucia de Noronha, Artur Junio Togneri Ferron, Carol Cristina Vagula de Almeida Silva,et al.
Springer Science and Business Media LLC
Abstract Background To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation. Methods Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed. Results TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05). Conclusion The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers. Trial registration Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.
Livia Interdonato, Giulio Ferrario, Marika Cordaro, Ramona D’Amico, Rosalba Siracusa, Roberta Fusco, Daniela Impellizzeri, Salvatore Cuzzocrea, Giancarlo Aldini, and Rosanna Di Paola
MDPI AG
Diet can modulate the different stages of inflammation due to the presence of bioactive compounds such as polyphenols. Apples are a great source of phenolic compounds that show anti-inflammatory and antioxidant properties, and these might be used as a dietary supplement and/or functional element in the treatment of chronic inflammatory illnesses. The aim of our study was to evaluate the anti-inflammatory and antioxidant actions of thinned apple polyphenol (TAP) extracts in a model of paw edema. The experimental model was induced in rats via subplantar injections of 1% λ-Carrageenan (CAR) in the right hind leg, and TAP extract was administered via oral gavage 30 min before and 1 h after the CAR injection at doses of 5 mg/kg and 10 mg/kg, respectively. The inflammatory response is usually quantified by the increase in the size of the paw (edema), which is maximal about 5 h after the injection of CAR. CAR-induced inflammation generates the release of pro-inflammatory mediators and reactive oxygen species (ROS). Furthermore, the inflammatory state induces the pain that involves the peripheral nociceptors, but above all it acts centrally at the level of the spinal cord. Our results showed that the TAP extracts reduced paw histological changes, neutrophil infiltration, mast cell degranulation, and oxidative stress. Additionally, the oral administration of TAP extracts decreased thermal and mechanical hyperalgesia, along with a reduction in spinal microglia and the markers of nociception. In conclusion, we demonstrate that TAP extract is able to modulate inflammatory, oxidative, and painful processes, and is also useful in the treatment of the symptoms associated with paw edema.
Beatrice Zoanni, Maura Brioschi, Alice Mallia, Erica Gianazza, Sonia Eligini, Marina Carini, Giancarlo Aldini, and Cristina Banfi
Wiley
The Human Plasma Proteome has always been the most investigated compartment in proteomics-based biomarker discovery, and is considered the largest and deepest version of the human proteome, reflecting the state of the body in health and disease. Even if efforts have been always dedicated to the refinement of proteomic approaches to investigate more deeply the plasma proteome, it should not be forgotten that also highly abundant plasma proteins, like human serum albumin (HSA), often neglected in these studies, might provide fundamental physiological functions in plasma, and should be better considered. This review summarizes the important roles of HSA in the context of cardiovascular diseases (CVD), and in particular in heart failure. Notwithstanding much attention has been historically directed toward the association of HSA levels and CVD risk, the advances in the field of mass spectrometry research allow also a better characterization of the effects of oxidative modifications that could alter not only the structure but also the function of HSA.
Juliana Silva Siqueira, Erika Tiemi Nakandakare-Maia, Taynara Aparecida Vieira, Thiago Luiz Novaga Palacio, Núbia Alves Grandini, Matheus Antônio Filiol Belin, Gisele Alborghetti Nai, Fernando Moreto, Alessandra Altomare, Giovanna Baron,et al.
MDPI AG
The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect of Bergamot leaves extract (BLE) on the crosstalk in the adipose tissue–liver axis of obese rats. For 20 weeks, Wistar rats were distributed into two groups: control (Control) and high sugar–fat (HSF) diet groups. Afterwards, the animals were redistributed into three groups for 10 weeks: control diet + vehicle (Control, n = 08), HSF + vehicle (HSF, n = 08), and HSF + BLE (HSF + BLE, n = 08). The BLE was carried out daily by gavage (50 mg/kg). The HSF group presented obesity, hyperglycemia, hypertriglyceridemia, insulin resistance, hepatic microvesicular steatosis, higher inflammation and oxidative stress in the liver and adipose tissue. In comparison to the HSF group, HSF + BLE animals showed protection by reducing the triglyceride levels, insulin resistance, inflammation and oxidative stress in hepatic and adipose tissues. BLE acted on the inflammation and oxidative stress in the adipose tissue–liver axis in obese rats when compared to the HSF group, which may have reflected on the improvement of insulin resistance and dyslipidemia.
Beatrice Zoanni, Gilda Aiello, Anne Negre-Salvayre, Giancarlo Aldini, Marina Carini, and Alfonsina D’Amato
MDPI AG
The lipid profile of skin is fundamental in the maintenance of the protective barrier against the external environment. Signaling and constitutive lipids of this large organ are involved in inflammation, metabolism, aging, and wound healing, such as phospholipids, triglycerides, FFA, and sphingomyelin. Skin exposure to ultraviolet (UV) radiation results in a photoaging process that is an accelerated form of aging. UV-A radiation deeply penetrates the dermis and promotes damage to DNA, lipids, and proteins by increasing the generation of reactive oxygen species (ROS). Carnosine, an endogenous β-alanyl-L-histidine dipeptide, demonstrated antioxidant properties that prevent photoaging and modification of skin protein profiling, making carnosine a compelling ingredient to consider for use in dermatology. The aim of this research was to investigate the modification of skin lipidome after UV-A treatment in presence or not of topic administration of carnosine. Quantitative analyses based on high-resolution mass spectrometry of nude mice skin-extracted lipids resulted in several modifications of barrier composition after UV-A radiation, with or without carnosine treatment. In total, 328 out of 683 molecules showed significant alteration—262 after UV-A radiation and 126 after UV-A and carnosine treatment versus controls. Importantly, the increased oxidized TGs after UV-A radiation, responsible of dermis photoaging, were completely reverted by carnosine application to prevent the UV-A damage. Network analyses also showed that the production of ROS and the calcium and TNF signaling were modulated by UV-A and carnosine. In conclusion, lipidome analyses attested the carnosine activity to prevent the UV-A damage, reducing the lipid oxidation, the inflammation, and the dysregulation of lipid skin barrier.