scholarly journals β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1038 ◽  
Author(s):  
Natasha Irrera ◽  
Angela D’Ascola ◽  
Giovanni Pallio ◽  
Alessandra Bitto ◽  
Federica Mannino ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Peroxisome Proliferator ◽  
Cb2 Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cannabinoid Receptor 2 ◽  
Proliferative Effect ◽  
Anti Inflammatory ◽  
Vitro Model ◽  
Inflammatory Effect

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK.

scholarly journals Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-γActivation

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Asha Jacob ◽  
Rongqian Wu ◽  
Mian Zhou ◽  
Ping Wang
Keyword(s):  
Clinical Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Commercial Grade ◽  
Inflammatory Agent ◽  
Anticancer Effects ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10–20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-γ(PPAR-γ) activation.

scholarly journals β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 326 ◽  
Author(s):  
Natasha Irrera ◽  
Angela D’Ascola ◽  
Giovanni Pallio ◽  
Alessandra Bitto ◽  
Emanuela Mazzon ◽  
...  
Keyword(s):  
Cross Talk ◽  
Articular Chondrocytes ◽  
Cannabinoid Receptor ◽  
Corn Oil ◽  
Peroxisome Proliferator ◽  
Cb2 Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cannabinoid Receptor 2 ◽  
Ppar Γ ◽  
Severity Of The Disease

β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.

Radioprotective effect of pioglitazone against genotoxicity induced by ionizing radiation in human healthy lymphocytes

2020 ◽  
Vol 18 ◽  
Author(s):  
Roya Kazemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Anti Inflammatory ◽  
Sensitizing Effect ◽  
Binucleated Lymphocytes ◽  
Inflammatory Effect

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in human healthy lymphocytes. Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when were exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). Conclusion: The anti-inflammatory property is suggested the mechanism action of PG for protection human lymphocytes against genotoxicity induced by ionizing radiation.

scholarly journals Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 222 ◽  
Author(s):  
Wenhui Jin ◽  
Longhe Yang ◽  
Zhiwei Yi ◽  
Hua Fang ◽  
Weizhu Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Inflammatory Factors ◽  
Lipid Mediator ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA–PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

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.

scholarly journals Inhibition of PPARγ in myeloid-lineage cells induces systemic inflammation, immunosuppression, and tumorigenesis

Blood ◽  
2012 ◽  
Vol 119 (1) ◽  
pp. 115-126 ◽  
Author(s):  
Lingyan Wu ◽  
Cong Yan ◽  
Magdalena Czader ◽  
Oded Foreman ◽  
Janice S. Blum ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Suppressor Cells ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Myeloid Lineage ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anti Inflammatory ◽  
Spleen And Lymph Nodes

Abstract Peroxisome proliferator–activated receptor-γ (PPARγ) is an anti-inflammatory molecule. To study its biologic function in myeloid cells, dominant-negative PPARγ (dnPPARγ) was overexpressed in a myeloid-specific bitransgenic mouse model. In this bitransgenic system, overexpression of the dnPPARγ-Flag fusion protein in myeloid-lineage cells abnormally elevated frequencies and total numbers of IL-7Rα−Lin−c-Kit+Sca-1−, Lin−/Scal+/c-Kit+, common myeloid, and granulocyte-monocyte progenitor populations in the BM. dnPPARγ overexpression led to up-regulation of IL-1β, IL-6, and TNFα in the blood plasma. As a result, CD11b+Ly6G+ cells were systemically increased in association with activation of Stat3, NF-κB, Erk1/2, and p38 molecules. Myeloid-derived suppressor cells (MDSCs) inhibited the proliferation and lymphokine production of wild-type CD4+ T cells in vitro. CD4+ T cells from doxycycline-treated bitransgenic mice displayed reduced proliferation and lymphokine release. Both CD4+ and CD8+ T-cell populations were decreased in doxycycline-treated bitransgenic mice. Multiple forms of carcinoma and sarcoma in the lung, liver, spleen, and lymph nodes were observed in doxycycline-treated bitransgenic mice. BM transplantation revealed that a myeloid-autonomous defect was responsible for MDSC expansion, immunosuppression, and tumorigenesis in these mice. These studies suggest that anti-inflammatory PPARγ in myeloid-lineage cells plays a key role in controlling pro-inflammatory cytokine synthesis, MDSC expansion, immunosuppression, and the development of cancer.

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