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Pharmaceuticals
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Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target
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Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 5503

Special Issue Editors

Dr. Sheila Leone

E-Mail Website
Guest Editor
Department of Pharmacy, “G. d’Annunzio” University, Via dei Vestini 31, 66100 Chieti, Italy
Interests: emotional behavior; anxiety; depression; inflammation; oxidative stress; obesity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Luigi Brunetti

E-Mail Website
Guest Editor
Department of Pharmacy, “G. d’Annunzio” University, Via dei Vestini 31, 66100 Chieti, Italy
Interests: emotional behavior; anxiety; depression; inflammation; oxidative stress; obesity
Special Issues, Collections and Topics in MDPI journals
Dr. Lucia Recinella

E-Mail Website
Guest Editor
Department of Pharmacy, “G. d’Annunzio” University, Via dei Vestini 31, 66100 Chieti, Italy
Interests: pharmaco-toxicological evaluations of herbal extracts; neuroendocrine regulation; GHRH deficiency
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute original research papers or review articles to the Special Issue “Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target”. Peroxisome Proliferator-Activated Receptors (PPARs) are important targets in various diseases, including obesity, metabolic syndrome, diabetes, and nonalcoholic fatty liver disease. PPARs are transcription factors that belong to the nuclear receptor superfamily. There are three subtypes of PPARs, designated as PPARα, γ, and β/δ, which exhibit different tissue expression profiles and modulate specific physiological functions. PPARs play a critical role in regulating the expression of multiple genes involved in the modulation of both glucose and lipid metabolism and energy homeostasis. Recent studies have shown that the activation of PPARs not only regulates multiple metabolic pathways, but also mediates various biological effects related to inflammation, apoptosis, oxidative stress, and vascular function.

The aim of this Special Issue is to further deepen the current knowledge of PPARs and their ligands in the prevention and treatment of metabolic disorders.

Dr. Sheila Leone
Prof. Dr. Luigi Brunetti
Dr. Lucia Recinella
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (3 papers)

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Research

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12 pages, 5609 KiB  
Article
The Nephroprotective Effects of the Allogeneic Transplantation with Mesenchymal Stromal Cells Were Potentiated by ω3 Stimulating Up-Regulation of the PPAR-γ
by Andreia Silva de Oliveira, Márcia Bastos Convento, Clara Versolato Razvickas, Bianca Castino, Ala Moana Leme, Rafael da Silva Luiz, Wesley Henrique da Silva, Maria Aparecida da Glória, Tatiana Pinotti Guirão, Eduardo Bondan, Nestor Schor and Fernanda Teixeira Borges
Pharmaceuticals 2023, 16(10), 1484; https://doi.org/10.3390/ph16101484 - 18 Oct 2023
Cited by 1 | Viewed by 1160
Abstract
Mesenchymal stromal cells (MSCs) obtained from bone marrow are a promising tool for regenerative medicine, including kidney diseases. A step forward in MSCs studies is cellular conditioning through specific minerals and vitamins. The Omega-3 fatty acids (ω3) are essential in regulating MSCs self-renewal, [...] Read more.
Mesenchymal stromal cells (MSCs) obtained from bone marrow are a promising tool for regenerative medicine, including kidney diseases. A step forward in MSCs studies is cellular conditioning through specific minerals and vitamins. The Omega-3 fatty acids (ω3) are essential in regulating MSCs self-renewal, cell cycle, and survival. The ω3 could act as a ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ). This study aimed to demonstrate that ω3 supplementation in rats could lead to the up-regulation of PPAR-γ in the MSCs. The next step was to compare the effects of these MSCs through allogeneic transplantation in rats subjected to unilateral ureteral obstruction (UUO). Independent of ω3 supplementation in the diet of the rats, the MSCs in vitro conserved differentiation capability and phenotypic characteristics. Nevertheless, MSCs obtained from the rats supplemented with ω3 stimulated an increase in the expression of PPAR-γ. After allogeneic transplantation in rats subjected to UUO, the ω3 supplementation in the rats enhanced some nephroprotective effects of the MSCs through a higher expression of antioxidant enzyme (SOD-1), anti-inflammatory marker (IL-10), and lower expression of the inflammatory marker (IL-6), and proteinuria. Full article
(This article belongs to the Special Issue Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target)
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16 pages, 2245 KiB  
Article
Anti-Inflammatory, Antioxidant, and WAT/BAT-Conversion Stimulation Induced by Novel PPAR Ligands: Results from Ex Vivo and In Vitro Studies
by Lucia Recinella, Barbara De Filippis, Maria Loreta Libero, Alessandra Ammazzalorso, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Letizia Giampietro, Serena Veschi, Alessandro Cama, Federica Mannino, Irene Gasparo, Alessandra Bitto, Rosa Amoroso, Luigi Brunetti and Sheila Leone
Pharmaceuticals 2023, 16(3), 346; https://doi.org/10.3390/ph16030346 - 24 Feb 2023
Cited by 3 | Viewed by 1728
Abstract
Activation of peroxisome proliferator-activated receptors (PPARs) not only regulates multiple metabolic pathways, but mediates various biological effects related to inflammation and oxidative stress. We investigated the effects of four new PPAR ligands containing a fibrate scaffold—the PPAR agonists (1a (αEC50 1.0 [...] Read more.
Activation of peroxisome proliferator-activated receptors (PPARs) not only regulates multiple metabolic pathways, but mediates various biological effects related to inflammation and oxidative stress. We investigated the effects of four new PPAR ligands containing a fibrate scaffold—the PPAR agonists (1a (αEC50 1.0 μM) and 1b (γEC50 0.012 μM)) and antagonists (2a (αIC50 6.5 μM) and 2b (αIC50 0.98 μM, with a weak antagonist activity on γ isoform))—on proinflammatory and oxidative stress biomarkers. The PPAR ligands 1a-b and 2a-b (0.1–10 μM) were tested on isolated liver specimens treated with lipopolysaccharide (LPS), and the levels of lactate dehydrogenase (LDH), prostaglandin (PG) E2, and 8-iso-PGF2α were measured. The effects of these compounds on the gene expression of the adipose tissue markers of browning, PPARα, and PPARγ, in white adipocytes, were evaluated as well. We found a significant reduction in LPS-induced LDH, PGE2, and 8-iso-PGF2α levels after 1a treatment. On the other hand, 1b decreased LPS-induced LDH activity. Compared to the control, 1a stimulated uncoupling protein 1 (UCP1), PR-(PRD1-BF1-RIZ1 homologous) domain containing 16 (PRDM16), deiodinase type II (DIO2), and PPARα and PPARγ gene expression, in 3T3-L1 cells. Similarly, 1b increased UCP1, DIO2, and PPARγ gene expression. 2a-b caused a reduction in the gene expression of UCP1, PRDM16, and DIO2 when tested at 10 μM. In addition, 2a-b significantly decreased PPARα gene expression. A significant reduction in PPARγ gene expression was also found after 2b treatment. The novel PPARα agonist 1a might be a promising lead compound and represents a valuable pharmacological tool for further assessment. The PPARγ agonist 1b could play a minor role in the regulation of inflammatory pathways. Full article
(This article belongs to the Special Issue Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target)
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Review

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11 pages, 677 KiB  
Review
PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies
by Suresh Victor, Ben Forbes, Anne Greenough and A. David Edwards
Pharmaceuticals 2023, 16(11), 1530; https://doi.org/10.3390/ph16111530 - 27 Oct 2023
Viewed by 1839
Abstract
Worldwide, three-quarters of a million babies are born extremely preterm (<28 weeks gestation) with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopulmonary dysplasia (BPD), and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) [...] Read more.
Worldwide, three-quarters of a million babies are born extremely preterm (<28 weeks gestation) with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopulmonary dysplasia (BPD), and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal period. In newborn animal models, pioglitazone has been shown to be protective against BPD, necrotising enterocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelopment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema, seen rarely in adults, may be avoided with a short treatment course. The other effects of pioglitazone, including improved glycaemic control and lipid metabolism, may provide added benefit in the context of prematurity. Currently, there is no formulation of pioglitazone suitable for administration to preterm babies. A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns. Full article
(This article belongs to the Special Issue Peroxisome Proliferator-Activated Receptor (PPAR): The Novel Pharmaceutical Target)
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