scholarly journals 3D-PHARMACOPHORE MODELLING OF OMEGA-3 DERIVATIVES WITH PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA AS AN ANTI-OBESITY AGENT

2021 ◽  
pp. 167-170
Author(s):  
IDA MUSFIROH ◽  
GINNA MEGAWATI ◽  
DEWI MARHENI DIAH HERAWATI ◽  
AGUS RUSDIN
Keyword(s):  
Functional Groups ◽  
Complex Structure ◽  
Pharmacophore Model ◽  
Docosapentaenoic Acid ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacophore Modelling ◽  
Ppar Γ ◽  
3D Pharmacophore

Objective: The aim of this work was to study the pharmacophore model of omega-3 derivatives with the PPAR-γ receptor using LigandScout 4.4.3 to investigate the important chemical interactions of complex structure. Methods: The methods consisted of structure preparation of nine chemical compounds derived from omega-3 fatty acids, database preparation, creating 3D Pharmacophore modelling, validation pharmacophore, and screening test compounds. Results: The result of the research showed that the omega-3 derivatives docosahexaenoic acid (DHA), when eicosapentaenoic acid (HPA), and docosapentaenoic acid (DPA) have the best pharmacophore fit values of 36.59; 36.56; and 36.56, respectively. According to the results of the pharmacophore study, the carbonyl and hydroxyl of the carboxylate functional groups become the active functional groups that exhibit hydrogen bonding interactions. While the alkyl chain (Ethyl and methyl groups) was the portion that can be modified to increase its activity. Conclusion: Omega-3 derivatives could be used as a lead drug for the powerful PPAR-γ receptor in the prevention and treatment of obesity.

Discovery of an Unexpected Similarity in Ligand Binding Between BRD4 and PPARγ

2019 ◽  
Author(s):  
Lina Humbeck ◽  
Jette Pretzel ◽  
Saskia Spitzer ◽  
Oliver Koch
Keyword(s):  
Cancer Therapy ◽  
Drug Targets ◽  
Synergistic Effects ◽  
Complex Structure ◽  
Peroxisome Proliferator ◽  
Resistance Development ◽  
Peroxisome Proliferator Activated Receptor ◽  
Starting Point ◽  
Fundamental Research ◽  
Important Drug

Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. A comprehensive scaffold-based analysis uncovered an unexpected relationship between bromodomain-containing protein 4 (BRD4) and peroxisome-proliferator activated receptor gamma (PPARγ). They are both important drug targets for cancer therapy and many more important diseases. Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such a dual-BRD4-PPARγ-modulator could show synergistic effects with a higher efficacy or delayed resistance development in, for example, cancer therapy. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.

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.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

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