scholarly journals Evaluation of selected 3D virtual screening tools for the prospective identification of peroxisome proliferator-activated receptor (PPAR) γ partial agonists

2016 ◽  
Vol 124 ◽  
pp. 49-62 ◽  
Author(s):  
T. Kaserer ◽  
V. Obermoser ◽  
A. Weninger ◽  
R. Gust ◽  
D. Schuster
Keyword(s):  
Virtual Screening ◽  
Screening Tools ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Agonists ◽  
Ppar Γ

scholarly journals Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36297 ◽  
Author(s):  
Marcelo Vizoná Liberato ◽  
Alessandro S. Nascimento ◽  
Steven D. Ayers ◽  
Jean Z. Lin ◽  
Aleksandra Cvoro ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Partial Agonists ◽  
Ppar Γ ◽  
Chain Fatty Acids

scholarly journals Development of a Protocol for Virtual Screening of PPARγ Weak Partial Agonists and Their Metabolites: Case Study on Naturally-derived Oleanane Triterpenoids

2021 ◽  
Vol 25 (2) ◽  
pp. 117-132
Author(s):  
Merilin Al Sharif ◽  
◽  
Petko Alov ◽  
Vessela Vitcheva ◽  
Antonia Diukendjieva ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Molecular Mechanisms ◽  
Partial Agonist ◽  
Mechanistic Explanation ◽  
Binding Mode ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Partial Agonists ◽  
Docking Protocol ◽  
Agonistic Activity

Triterpenoids are well known metabolic syndrome (MetS) modulators. One of the suggested molecular mechanisms of action involves peroxisome proliferator-activated receptor gamma (PPARγ) activation. In this study we aimed to: (i) develop a virtual screening (VS) protocol for PPARγ weak partial agonists, (ii) predict potential metabolic transformations of naturally-derived triterpenoids, and (iii) perform VS of the triterpenoids and their metabolites. The NIH PubMed system was searched for publications about naturally-derived oleanane triterpenoids which are agonists or up-regulators of PPARγ. Structure- and ligand-based methods were combined in the development of the VS protocol. Metabolites were predicted using Meteor Nexus expert system (Lhasa Limited). Two in-house virtual libraries of PPARγ weak partial agonists and naturally-derived triterpenoids with their predicted metabolites were compiled. The pharmacophore-based docking protocol was applied for VS of the collected triterpenoids. Most of the docking poses reproduced the binding mode of caulophyllogenin (a weak partial agonist) in a complex with PPARγ (PDB ID 5F9B). Our results contribute to the mechanistic explanation of the effects of triterpenoids suggesting possible weak partial agonistic activity toward PPARγ. This research can direct further studies on triterpenoids’ role in MetS modulation. The developed protocol can be applied for VS of any PPARγ weak partial agonists.

scholarly journals Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway

2021 ◽  
Author(s):  
Serena Stopponi ◽  
Yannick Fotio ◽  
Carlo Cifani ◽  
Hongwu Li ◽  
Carolina L Haass-Koffler ◽  
...  
Keyword(s):  
Oral Administration ◽  
Alcohol Drinking ◽  
Andrographis Paniculata ◽  
Peroxisome Proliferator ◽  
Herbaceous Plant ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Treatment Administration ◽  
Dried Extract

Abstract Background and aims Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats. Methods The present study evaluated whether A. paniculata reduces alcohol drinking and relapse in msP rats by activating PPARγ. Results Oral administration of an A. paniculata dried extract (0, 15, 150 mg/kg) lowered voluntary alcohol consumption in a dose-dependent manner and achieved ~65% reduction at the dose of 450 mg/kg. Water and food consumption were not affected by the treatment. Administration of Andrographolide (5 and 10 mg/kg), the main active component of A. paniculata, also reduced alcohol drinking. This effect was suppressed by the selective PPARγ antagonist GW9662. Subsequently, we showed that oral administration of A. paniculata (0, 150, 450 mg/kg) prevented yohimbine- but not cues-induced reinstatement of alcohol seeking. Conclusions Results point to A. paniculata-mediated PPARγactivation as a possible therapeutic strategy to treat alcohol use disorder.

scholarly journals Diet and PPARG2 Pro12Ala Polymorphism Interactions in Relation to Cancer Risk: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 261
Author(s):  
Lieu Tran ◽  
Gerd Bobe ◽  
Gayatri Arani ◽  
Yang Zhang ◽  
Zhenzhen Zhang ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Dietary Factors ◽  
Dietary Fats ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Allele Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Complex Relation ◽  
Ppar Γ ◽  
Pubmed Database

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.

scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

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