Elzbieta Janda

Researcher of Molecular Biology

Name Elzbieta
Surname Janda
Institution University Magna Graecia, Catanzaro
Telephone +39 0961 369 4143
E-Mail janda@unicz.it
Address Department of Health Sciences University Magna Graecia, Catanzaro Campus Germaneto Edificio Bioscienze, livello 5 88100 Catanzaro, Italy
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Elzbieta Janda

Member PUBLICATIONS

  • Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction.

    Publication Date: 16/03/2019 on Antioxidants (Basel, Switzerland)
    by La Russa D, Giordano F, Marrone A, Parafati M, Janda E, Pellegrino D
    DOI: 10.3390/antiox8030066

    Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress.

  • S29434, a quinone reductase 2 inhibitor: main biochemical and cellular characterization.

    Publication Date: 19/12/2018 on Molecular pharmacology
    by Boutin JA, Bouillaud F, Janda E, Gacsalyi I, Guillaumet G, Hirsch EC, Kane DA, Nepveu F, Reybier K, Dupuis P, Bertrand M, Chhour M, Le Diguarher T, Antoine M, Brebner K, Da Costa H, Ducrot P, Giganti A, Goswami V, Guedouari H, Michel PP, Patel A, Paysant J, Stojko J, Viaud-Massuard MC, Ferry G
    DOI: 10.1124/mol.118.114231

    Quinone reductase 2 (QR2, E.C. 1.10.5.1) is an enzyme with a feature that has attracted attention for several decades: in standard conditions, instead of recognizing NAD(P)H as an electron donor, it recognizes putative metabolites of NADH such as N-methyl- and N-ribosyl-dihydronicotinamide. QR2 has been particularly associated with reactive oxygen species and memory, strongly suggesting a link among QR2 (as a possible key element in pro-oxidation), autophagy, and neurodegeneration. In molecular and cellular pharmacology, understanding physiopathological associations can be difficult because of a lack of specific and powerful tools. Here we present a thorough description of the potent, nanomolar inhibitor S29434 (IC50 = 5 to 16 nM) of QR2 at different organizational levels. We provide full detailed syntheses; describe its co-crystallization with and behavior at QR2 on a millisecond timeline; show that it penetrates cell membranes and inhibits QR2-mediated ROS production within the 100 nM range; and describe its actions in several in vivo models, and lack of actions in various ROS-producing systems. The inhibitor is fairly stable in vivo, penetrates cells, specifically inhibits QR2, and shows activities that suggest a key role for this enzyme in different pathological conditions including neurodegenerative diseases.

  • Bergamot Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by "Junk Food": Evidence for Anti-Inflammatory Activity.

    Publication Date: 01/11/2018 on Nutrients
    by Parafati M, Lascala A, La Russa D, Mignogna C, Trimboli F, Morittu VM, Riillo C, Macirella R, Mollace V, Brunelli E, Janda E
    DOI: 10.3390/nu10111604

    Wrong alimentary behaviors and so-called "junk food" are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The "junk food" toxicity can be studied in "cafeteria" (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot () flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 () mRNA expression and increasing anti-inflammatory , which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

  • Qualitative and quantitative analysis of the proautophagic activity of Citrus flavonoids from Bergamot Polyphenol Fraction.

    Publication Date: 31/05/2018 on Data in brief
    by Janda E, Salerno R, Martino C, Lascala A, La Russa D, Oliverio M
    DOI: 10.1016/j.dib.2018.05.139

    Bergamot Polyphenol Fraction (BPF®) is a natural mixture of flavonoids extracted from processed bergamot fruits. It has been shown to counteract cardiovascular risk factors and to prevent liver steatosis in rats and patients. Hepatic effects of BPF correlate with its ability to stimulate liver autophagy. Six aglyconic flavonoids have been identified in the proautophagic fraction of the hydrolysis product of BPF (A-BPF): naringenin, hesperetin, eridictyol, diosmetin, apigenin and luteolin. We report here the output parameters of high resolution mass spectrometry analysis of these flavonoids and chemical structures of their parent compounds. The second set of data shows the proautophagic activity of BPF flavonoids in a hepatic cell line HepG2 analyzed by a flow cytometry approach. The method is based on the red to green fluorescence intensity ratio analysis of DsRed -LC3- GFP, which is stably expressed in HepG2 cells. Proportional analysis of ATG indexes allowed us to address a relative contribution of individual compounds to the proautophagic activity of the A-BPF mixture and evaluate if the effect was additive. Qualitative analysis of ATG indexes compared the effects of flavonoids at equal concentrations in the presence and absence of palmitic acid and chloroquine. The Excel files reporting the analysis of flow cytometry data are available in the public repository.

  • Microglial Phagocytosis and Its Regulation: A Therapeutic Target in Parkinson's Disease?

    Publication Date: 27/04/2018 on Frontiers in molecular neuroscience
    by Janda E, Boi L, Carta AR
    DOI: 10.3389/fnmol.2018.00144

    The role of phagocytosis in the neuroprotective function of microglia has been appreciated for a long time, but only more recently a dysregulation of this process has been recognized in Parkinson's disease (PD). Indeed, microglia play several critical roles in central nervous system (CNS), such as clearance of dying neurons and pathogens as well as immunomodulation, and to fulfill these complex tasks they engage distinct phenotypes. Regulation of phenotypic plasticity and phagocytosis in microglia can be impaired by defects in molecular machinery regulating critical homeostatic mechanisms, including autophagy. Here, we briefly summarize current knowledge on molecular mechanisms of microglia phagocytosis, and the neuro-pathological role of microglia in PD. Then we focus more in detail on the possible functional role of microglial phagocytosis in the pathogenesis and progression of PD. Evidence in support of either a beneficial or deleterious role of phagocytosis in dopaminergic degeneration is reported. Altered expression of target-recognizing receptors and lysosomal receptor CD68, as well as the emerging determinant role of α-synuclein (α-SYN) in phagocytic function is discussed. We finally discuss the rationale to consider phagocytic processes as a therapeutic target to prevent or slow down dopaminergic degeneration.

  • Analysis of proautophagic activities of Citrus flavonoids in liver cells reveals the superiority of a natural polyphenol mixture over pure flavones.

    Publication Date: 26/04/2018 on The Journal of nutritional biochemistry
    by Lascala A, Martino C, Parafati M, Salerno R, Oliverio M, Pellegrino D, Mollace V, Janda E
    DOI: 10.1016/j.jnutbio.2018.04.005

    Autophagy dysfunction has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Natural compounds present in bergamot polyphenol fraction (BPF) prevent NAFLD and induce autophagy in rat livers. Here, we employed HepG2 cells expressing DsRed-LC3-GFP, a highly sensitive model system to screen for proautophagic compounds present in BPF. BPF induced autophagy in a time- and dose-dependent fashion and the effect was amplified in cells loaded with palmitic acid. Autophagy was mediated by the hydrophobic fraction of acid-hydrolyzed BPF (A-BPF), containing six flavanone and flavone aglycones as identified by liquid chromatography-high-resolution mass spectrometry. Among them, naringenin, hesperitin, eriodictyol and diosmetin were weak inducers of autophagy. Apigenin showed the strongest and dose-dependent proautophagic activity at early time points (6 h). Luteolin induced a biphasic autophagic response, strong at low doses and inhibitory at higher doses. Both flavones were toxic in HepG2 cells and in differentiated human liver progenitors HepaRG upon longer treatments (24 h). In contrast, BPF and A-BPF did not show any toxicity, but induced a persistent increase in autophagic flux. A mixture of six synthetic aglycones mimicking A-BPF was sufficient to induce a similar autophagic response, but it was mildly cytotoxic. Thus, while six main BPF flavonoids fully account for its proautophagic activity, their combined effect is not sufficient to abrogate cytotoxicity of individual compounds. This suggests that a natural polyphenol phytocomplex, such as BPF, is a safer and more effective strategy for the treatment of NAFLD than the use of pure flavonoids.

  • Boosting phagocytosis and anti-inflammatory phenotype in microglia mediates neuroprotection by PPARγ agonist MDG548 in Parkinson's disease.

    Publication Date: 23/03/2018 on British journal of pharmacology
    by Lecca D, Janda E, Mulas G, Diana A, Martino C, Angius F, Spolitu S, Antonietta Casu M, Simbula G, Boi L, Batetta B, Spiga S, Carta AR
    DOI: 10.1111/bph.14214

    Microglia phenotype and phagocytic activity are deregulated in Parkinson's disease (PD). Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are neuroprotective in experimental PD, but their role in regulating microglial phenotype and phagocytosis has been poorly investigated. We addressed it by using the PPARγ agonist MDG548.

  • Medicinal Herbs and Their Active Compounds for Fatty Liver Diseases.

    Publication Date: 01/01/2017 on Evidence-based complementary and alternative medicine : eCAM
    by Son CG, Wei Z, Raghavendran HB, Wang JH, Janda E
    DOI: 10.1155/2017/3612478
  • Bergamot polyphenol fraction prevents nonalcoholic fatty liver disease via stimulation of lipophagy in cafeteria diet-induced rat model of metabolic syndrome.

    Publication Date: 01/09/2015 on The Journal of nutritional biochemistry
    by Parafati M, Lascala A, Morittu VM, Trimboli F, Rizzuto A, Brunelli E, Coscarelli F, Costa N, Britti D, Ehrlich J, Isidoro C, Mollace V, Janda E
    DOI: 10.1016/j.jnutbio.2015.03.008

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries. Defective autophagy of lipid droplets (LDs) in hepatocytes, also known as lipophagy, has recently been identified as a possible pathophysiological mechanism of NAFLD. Experimental and epidemiological evidence suggests that dietary polyphenols may prevent NAFLD. To address this hypothesis and analyze the underlying mechanisms, we supplemented bergamot polyphenol fraction (BPF) to cafeteria (CAF) diet-fed rats, a good model for pediatric metabolic syndrome and NAFLD. BPF treatment (50 mg/kg/day supplemented with drinking water, 3 months) potently counteracted the pathogenic increase of serum triglycerides and had moderate effects on blood glucose and obesity in this animal model. Importantly, BPF strongly reduced hepatic steatosis as documented by a significant decrease in total lipid content (-41.3% ± 12% S.E.M.), ultrasound examination and histological analysis of liver sections. The morphometric analysis of oil-red stained sections confirmed a dramatic reduction in LDs parameters such as total LD area (48.5% ± 15% S.E.M.) in hepatocytes from CAF+BPF rats. BPF-treated livers showed increased levels of LC3 and Beclin 1 and reduction of SQSTM1/p62, suggesting autophagy stimulation. Consistent with BPF stimulation of lipophagy, higher levels of LC3II were found in the LD subcellular fractions of BPF-expose livers. This study demonstrates that the liver and its lipid metabolism are the main targets of bergamot flavonoids, supporting the concept that supplementation of BPF is an effective strategy to prevent NAFLD.

  • Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection.

    Publication Date: 01/01/2015 on Autophagy
    by Janda E, Lascala A, Carresi C, Parafati M, Aprigliano S, Russo V, Savoia C, Ziviani E, Musolino V, Morani F, Isidoro C, Mollace V
    DOI: 10.1080/15548627.2015.1058683

    Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular target of neurotoxins in the brain. PQ decreased the basal levels of LC3-II and LC3-positive vesicles, and its colocalization with lysosomal markers, both in the absence and presence of chloroquine. This was paralleled by increased number and size of SQSTM1/p62 aggregates. Downregulation of autophagy was also observed in cells chronically exposed to hydrogen peroxide or nonlethal concentrations of PQ, and it was associated with a reduced astrocyte capability to protect dopaminergic cells from OS in co-cultures. Surprisingly, PQ treatment led to inhibition of MTOR, activation of MAPK8/JNK1 and MAPK1/ERK2-MAPK3/ERK1 and upregulation of BECN1/Beclin 1 expression, all signals typically correlating with induction of autophagy. Reduction of OS by NMDPEF, a specific NQO2 inhibitor, but not by N-acetylcysteine, abrogated the inhibitory effect of PQ and restored autophagic flux. Activation of NQO2 by PQ or menadione and genetic manipulation of its expression confirmed the role of this enzyme in the inhibitory action of PQ on autophagy. PQ did not induce NFE2L2/NRF2, but when it was co-administered with NMDPEF NFE2L2 activity was enhanced in a SQSTM1-independent fashion. Thus, a prolonged OS in astrocytes inhibits LC3 lipidation and impairs autophagosome formation and autophagic flux, in spite of concomitant activation of several pro-autophagic signals. These findings outline an unanticipated neuroprotective role of astrocyte autophagy and identify in NQO2 a novel pharmacological target for its positive modulation.