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
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
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.
Erika Tiemi Nakandakare-Maia, Juliana Silva Siqueira, Artur Junio Togneri Ferron, Taynara Aparecida Vieira, Thiago Luiz Novaga Palacio, Núbia Alves Grandini, Jéssica Leite Garcia, Matheus Antonio Belin, Alessandra Altomare, Giovanna Baron,et al.
Elsevier BV
Larissa Della Vedova, Francesca Gado, Taynara A. Vieira, Núbia A. Grandini, Thiago L. N. Palácio, Juliana S. Siqueira, Marina Carini, Ezio Bombardelli, Camila R. Correa, Giancarlo Aldini,et al.
MDPI AG
The present paper reports a sustainable raw material obtained from the by-products derived from the industrial production of bergamot (Citrus × Bergamia Risso & Poiteau) essential oils. The procedure to obtain the raw material is designed to maintain as much of the bioactive components as possible and to avoid expensive chemical purification. It consists of spray-drying the fruit juice obtained by squeezing the fruits, which is mixed with the aqueous extract of the pulp, i.e., the solid residue remained after fruit pressing. The resulting powder bergamot juice (PBJ) contains multiple bioactive components, in particular, among others, soluble fibers, polyphenols and amino-acid betaines, such as stachydrine and betonicine. LC-MS analysis identified 86 compounds, with hesperetin, naringenin, apigenin and eridictyol glucosides being the main components. In the second part of the paper, dose-dependent anti-inflammatory activity of PBJ and of stachydrine was found, but neither of the compounds were effective in activating Nrf2. PBJ was then found to be effective in an in vivo model of a metabolic syndrome induced by a high-sugar, high-fat (HSF) diet and evidenced by a significant increase of the values related to a set of parameters: blood glucose, triglycerides, insulin resistance, systolic blood pressure, visceral adipose tissue and adiposity index. PBJ, when given to control rats, did not significantly change these values; in contrast, they were found to be greatly affected in rats receiving an HSF diet. The in vivo effect of PBJ can be ascribed not only to bergamot polyphenols with well-known anti-inflammatory, antioxidant and lipid-regulating effects, but also to the dietary fibers and to the non-phenolic constituents, such as stachydrine. Moreover, since PBJ was found to affect energy homeostasis and to regulate food intake, a mechanism on the regulation of energy homeostasis through leptin networking should also be considered and deserves further investigation.
Alice Uwineza, Ian Cummins, Miguel Jarrin, Alexia A. Kalligeraki, Stephen Barnard, Marco Mol, Genny Degani, Alessandra A. Altomare, Giancarlo Aldini, An Schreurs,et al.
Elsevier BV
Gilda Aiello, Francesca Rescigno, Marisa Meloni, Beatrice Zoanni, Giancarlo Aldini, Marina Carini, and Alfonsina D’Amato
MDPI AG
Dermis fibroblasts are very sensitive to penetrating UVA radiation and induce photo-damage. To protect skin cells against this environmental damage, there is an urgent need for effective compounds, specifically targeting UVA-induced mitochondrial injury. This study aimed to analyze the effect of carnosine on the proteome of UVA-irradiated human skin fibroblast, cultured in a three-dimensional (3D) biological system recapitulating dermal compartment as a test system to investigate the altered cellular pathways after 48 h and 7 days of culture with or without carnosine treatment. The obtained results indicate that UVA dysregulates Oxidative Phosphorylation, the Fibrosis Signaling Pathway, Glycolysis I and Nrf2-mediated Oxidative Stress Response. Carnosine exercises provide a protective function against the harmful effects of UVA radiation by activating the Nrf2 pathway with the upregulations of some ROS-detoxifying enzymes such as the glutathione S-transferase (GST) protein family. Additionally, carnosine regulates the activation of the Epithelial Adherens Junction and Wound Healing Signaling Pathway by mediating the activation of structural proteins such as vinculin and zyxin as well as fibronectin 1 and collagen type XVIII alpha 1 chain against UVA-induced changes.
Rebecca Ferrisi, Beatrice Polini, Caterina Ricardi, Francesca Gado, Kawthar A. Mohamed, Giovanna Baron, Salvatore Faiella, Giulio Poli, Simona Rapposelli, Giuseppe Saccomanni,et al.
MDPI AG
Very recently, we have developed a new generation of ligands targeting the cannabinoid receptor type 2 (CB2R), namely JR compounds, which combine the pharmacophoric portion of the CB2R positive allosteric modulator (PAM), EC21a, with that of the CB2R selective orthosteric agonist LV62, both synthesized in our laboratories. The functional examination enabled us to identify JR14a, JR22a, and JR64a as the most promising compounds of the series. In the current study, we focused on the assessment of the bitopic (dualsteric) nature of these three compounds. Experiments in cAMP assays highlighted that only JR22a behaves as a CB2R bitopic (dualsteric) ligand. In parallel, computational studies helped us to clarify the binding mode of these three compounds at CB2R, confirming the bitopic (dualsteric) nature of JR22a. Finally, the potential of JR22a to prevent neuroinflammation was investigated on a human microglial cell inflammatory model.
Francesca Gado, Giulio Ferrario, Larissa Della Vedova, Beatrice Zoanni, Alessandra Altomare, Marina Carini, Giancarlo Aldini, Alfonsina D’Amato, and Giovanna Baron
MDPI AG
Plant secondary metabolites, known as phytochemicals, have recently gained much attention in light of the “circular economy”, to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included. This review aims to provide a thorough overview of the main studies reported in the literature concerning apple phytochemicals, mostly polyphenols, in cancer prevention. Although there are many different mechanisms targeted by phytochemicals, the Nrf2 and NF-κB signaling pathways are the ones this review will be focused on, highlighting also the existing crosstalk between these two systems.
M SCHÖN, I JUST, P KRUMPOLEC, P BLAŽÍČEK, L VALKOVIČ, G ALDINI, C-L TSAI, B DE COURTEN, M KRŠŠÁK, B UKROPCOVÁ,et al.
Institute of Physiology of the Czech Academy of Sciences
Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0±2.7 kg/m2) adults (40.1±6.2 years). Muscle carnosine concentration (Proton Magnetic Resonance Spectroscopy; 1H-MRS), dynamics of muscle energy metabolism (Phosphorus Magnetic Resonance Spectroscopy; 31P-MRS), body composition (Magnetic Resonance Imaging; MRI), resting energy expenditure (indirect calorimetry), glucose tolerance (oGTT), habitual physical activity (accelerometers), serum carnosine and carnosinase-1 content/activity (ELISA), albumin glycation, urinary carnosine and carnosine-propanal concentration (mass spectrometry) were measured. Supplementation-induced increase in muscle carnosine was paralleled by improved dynamics of muscle post-exercise phosphocreatine recovery, decreased serum albumin glycation and enhanced urinary carnosine-propanal excretion (all p<0.05). Magnitude of supplementation-induced muscle carnosine accumulation was higher in individuals with lower baseline muscle carnosine, who had lower BMI, higher physical activity level, lower resting intramuscular pH, but similar muscle mass and dietary protein preference. Level of supplementation-induced increase in muscle carnosine correlated with reduction of protein glycation, increase in reactive carbonyl species sequestering, and acceleration of muscle post-exercise phosphocreatine recovery.
Thiago Luiz Novaga Palacio, Juliana Silva Siqueira, Bruno Henrique de Paula, Rebeca Mayara Padilha Rego, Taynara Aparecida Vieira, Giovanna Baron, Alessandra Altomare, Artur Junio Togneri Ferron, Giancarlo Aldini, Hugo Tadashi Kano,et al.
Informa UK Limited
Martina Bottoni, Giovanna Baron, Francesca Gado, Fabrizia Milani, Laura Santagostini, Lorenzo Colombo, Paola Sira Colombo, Elisabetta Caporali, Alberto Spada, Marco Biagi,et al.
MDPI AG
A multidisciplinary investigation on Achillea moschata Wulfen (Asteraceae) is outlined herein. This work, part of the European Interreg Italy–Switzerland B-ICE project, originated from an ethnobotanical survey performed in Chiesa in Valmalenco (Sondrio, Lombardy, Northern Italy) in 2019–2021 which highlighted this species’ relevance of use in folk medicine to treat gastrointestinal diseases. In addition, this contribution included analyses of the: (a) phytochemical profile of the aqueous and methanolic extracts of the dried flower heads using LC-MS/MS; (b) morpho-anatomy and histochemistry of the vegetative and reproductive organs through Light, Fluorescence, and Scanning Electron Microscopy; (c) biological activity of the aqueous extract concerning the antioxidant and anti-inflammatory potential through cell-based in vitro models. A total of 31 compounds (5 phenolic acids, 13 flavonols, and 13 flavones) were detected, 28 of which included in both extracts. Covering and secreting trichomes were observed: the biseriate 10-celled glandular trichomes prevailing on the inflorescences represented the main sites of synthesis of the polyphenols and flavonoids detected in the extracts, along with volatile terpenoids. Finally, significant antioxidant and anti-inflammatory activities of the aqueous extract were documented, even at very low concentrations; for the first time, the in vitro tests allowed us to formulate hypotheses about the mechanism of action. This work brings an element of novelty due to the faithful reproduction of the traditional aqueous preparation and the combination of phytochemical and micromorphological research approaches.
Juliana Silva Siqueira, Taynara Aparecida Vieira, Erika Tiemi Nakandakare-Maia, Thiago Luiz Novaga Palacio, Felipe Sarzi, Jessica Leite Garcia, Bruno Henrique de Paula, Silmeia Garcia Zanati Bazan, Giovanna Baron, Luigi Tucci,et al.
Elsevier BV
Filippo Moncalvo, Elisa Lacroce, Giulia Franzoni, Alessandra Altomare, Elisa Fasoli, Giancarlo Aldini, Alessandro Sacchetti, and Francesco Cellesi
American Chemical Society (ACS)