scholarly journals Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2076 ◽  
Author(s):  
Carmen Ciavarella ◽  
Ilenia Motta ◽  
Sabrina Valente ◽  
Gianandrea Pasquinelli
Keyword(s):  
Peroxisome Proliferator ◽  
Cytokine Storm ◽  
Disease Treatment ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dual Approach ◽  
Ppar Γ ◽  
Inflammatory Drugs ◽  
Coronavirus Infection ◽  
Anti Inflammatory ◽  
Dietary Strategies

The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.

scholarly journals Apple Flavonols Mitigate Adipocyte Inflammation and Promote Angiogenic Factors in LPS- and Cobalt Chloride-Stimulated Adipocytes, in Part by a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1386 ◽  
Author(s):  
Danyelle M. Liddle ◽  
Meaghan E. Kavanagh ◽  
Amanda J. Wright ◽  
Lindsay E. Robinson
Keyword(s):  
Mrna Expression ◽  
Cobalt Chloride ◽  
Nuclear Factor Κb ◽  
Diglycidyl Ether ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Anti Inflammatory

Adipose tissue (AT) expansion induces local hypoxia, a key contributor to the chronic low-grade inflammation that drives obesity-associated disease. Apple flavonols phloretin (PT) and phlorizin (PZ) are suggested anti-inflammatory molecules but their effectiveness in obese AT is inadequately understood. Using in vitro models designed to reproduce the obese AT microenvironment, 3T3-L1 adipocytes were cultured for 24 h with PT or PZ (100 μM) concurrent with the inflammatory stimulus lipopolysaccharide (LPS; 10 ng/mL) and/or the hypoxia mimetic cobalt chloride (CoCl2; 100 μM). Within each condition, PT was more potent than PZ and its effects were partially mediated by peroxisome proliferator-activated receptor (PPAR)-γ (p < 0.05), as tested using the PPAR-γ antagonist bisphenol A diglycidyl ether (BADGE). In LPS-, CoCl2-, or LPS + CoCl2-stimulated adipocytes, PT reduced mRNA expression and/or secreted protein levels of inflammatory and macrophage chemotactic adipokines, and increased that of anti-inflammatory and angiogenic adipokines, which was consistent with reduced mRNA expression of M1 polarization markers and increased M2 markers in RAW 264.7 macrophages cultured in media collected from LPS + CoCl2-simulated adipocytes (p < 0.05). Further, within LPS + CoCl2-stimulated adipocytes, PT reduced reactive oxygen species accumulation, nuclear factor-κB activation, and apoptotic protein expression (p < 0.05). Overall, apple flavonols attenuate critical aspects of the obese AT phenotype.

Peroxisome proliferator-activated receptor-γ inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells

2006 ◽  
Vol 291 (1) ◽  
pp. L84-L90 ◽  
Author(s):  
Sung Yong Lee ◽  
Eun Joo Kang ◽  
Gyu Young Hur ◽  
Ki Hwan Jung ◽  
Hye Cheol Jung ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Responses ◽  
Cigarette Smoke Exposure ◽  
Etiologic Factor ◽  
Peroxisome Proliferator ◽  
Cell Hyperplasia ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mucin Production ◽  
Ppar Γ ◽  
Anti Inflammatory

The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the ligand-activated nuclear receptor superfamily. PPAR-γ is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-γ agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-γ in smoke-induced mucin production. In this study, we investigated the effect of PPAR-γ agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-γ agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and downregulation of Akt expression. This study demonstrates that PPAR-γ agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium.

scholarly journals New Hydroquinone Monoterpenoid and Cembranoid-Related Metabolites from the Soft Coral Sarcophyton tenuispiculatum

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 8
Author(s):  
Tzu-Yin Huang ◽  
Chiung-Yao Huang ◽  
Shu-Rong Chen ◽  
Jing-Ru Weng ◽  
Tzu-Hsuan Tu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Soft Coral ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Biological Assays ◽  
Chemical Structures ◽  
Ppar Γ ◽  
Spectroscopic Analyses ◽  
Anti Inflammatory ◽  
Factor Assay

Chemical investigation of the marine soft coral Sarcophyton tenuispiculatum resulted in the isolation of a 1,4-dihydrobenzoquinone, sarcotenuhydroquinone (1), three new cembranoids, sarcotenusenes A‒C (2‒4), and ten previously reported metabolites 5–14. The chemical structures of all isolated metabolites were determined by detailed spectroscopic analyses. In biological assays, anti-inflammatory, cytotoxic, and peroxisome proliferator-activated receptor γ (PPAR-γ) transcription factor assays of all compounds were performed. None of the isolated compounds were found to exhibit activity in the PPAR-γ transcription factor assay. The anti-inflammatory assays showed that (+)-7α,8β-dihydroxydeepoxysarcophine (13) inhibited the production of IL-1β to 56 ± 1% at a concentration of 30 µM in lipopolysaccharide (LPS)-stimulated J774A.1 macrophage cells. In addition, 1 and 2 were found to exhibit cytotoxicity towards a panel of cancer cell lines.

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