A bioactive fraction of Pterocarpus santalinus inhibits adipogenesis and inflammation in 3T3-L1 cells via modulation of PPAR-γ/SREBP-1c and TNF-α/IL-6

3 Biotech ◽  
2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Karunakaran Reddy Sankaran ◽  
Muni Swamy Ganjayi ◽  
Lokanatha Oruganti ◽  
Appa Rao Chippada ◽  
Balaji Meriga
Keyword(s):  
Ppar Γ ◽  
Tnf Α ◽  
Pterocarpus Santalinus ◽  
Bioactive Fraction

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.

15 Deoxy Δ12,14 PGJ2 Induces Procoagulant Activity in Cultured Human Endothelial Cells

2002 ◽  
Vol 87 (03) ◽  
pp. 523-529 ◽  
Author(s):  
Shaoping Xie ◽  
David O’Regan ◽  
Vijay Kakkar ◽  
Michael Scully
Keyword(s):  
Endothelial Cells ◽  
Peroxisome Proliferator ◽  
Endothelial Protein C Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Affinity Ligand ◽  
Ppar Γ ◽  
Tnf Α ◽  
Ea.Hy926 Cells ◽  
High Affinity Ligand ◽  
Feedback Regulator

Summary15 deoxy Δ12,14 PGJ2 (15d-PGJ2), a high affinity ligand of peroxisome proliferator-activated receptor γ (PPAR γ has been proposed to act as a negative feedback regulator of the inflammatory response. We investigated the effect of 15d-PGJ2 on the anticoagulant property of endothelial cells. 15d-PGJ2 stimulated a moderate but sustained increase in tissue factor (TF) activity in HUVECs and EA.hy926 cells while causing a partial loss of thrombomodulin (TM) activity. When cells were co-treated with 15d-PGJ2 and TNF-α, the subsequent elevation of TF activity was synergistically increased over that of cells treated with TNF-α, alone and the decline of TF activity after 24 h was less marked than TNF-α, alone. The induction of TF by 15d-PGJ2 alone and in combination with TNF-α, was reduced in the presence of PD 98059, suggesting the participation of the MEK/ERK pathway. The thiazolidinedione PPAR γ agonist ciglitazone had no effect on TF levels but reduced the expression of endothelial protein C receptor. The ability of 15d-PGJ2 to enhance a procoagulant phenotype arising from TNF-α, suggests a pro-inflammatory role for the prostaglandin.

TNF-α reduces g0s2 expression and stimulates lipolysis through PPAR-γ inhibition in 3T3-L1 adipocytes

Cytokine ◽  
2014 ◽  
Vol 69 (2) ◽  
pp. 196-205 ◽  
Author(s):  
Dan Jin ◽  
Jun Sun ◽  
Jing Huang ◽  
Yiduo He ◽  
An Yu ◽  
...  
Keyword(s):  
Ppar Γ ◽  
Tnf Α

scholarly journals CCL2 is Modulated by Cytokines and PPAR-γ in Anaplastic Thyroid Cancer

2018 ◽  
Vol 18 (3) ◽  
pp. 458-466 ◽  
Author(s):  
Silvia Martina Ferrari ◽  
Giusy Elia ◽  
Simona Piaggi ◽  
Enke Baldini ◽  
Salvatore Ulisse ◽  
...  
Keyword(s):  
Anaplastic Thyroid Cancer ◽  
Serum Levels ◽  
Anaplastic Thyroid Carcinoma ◽  
Ppar Γ ◽  
Tnf Α ◽  
Proliferation And Apoptosis ◽  
Different Types ◽  
Level Versus ◽  
Ifn Γ ◽  
Growth Promoting

Background and Objective: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. Methods: We tested in “primary human anaplastic thyroid carcinoma (ATC) cells” (ANA) versus “normal thyroid follicular cells” (TFC): a) CCL2 secretion basally, after IFN-γ and/or TNF-α stimulation; b) PPARγ activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA. Results: ANA produced basally CCL2, at a higher level versus TFC. IFN-γ or TNF-α dose-dependently induced the CCL2 release in 3/6 or 5/6 ANA, respectively, but in all TFC. IFN-γ+TNF-α induced a synergistic release of CCL2 in all TFC, but only in 1/6 ATC. TZDs exerted an inhibition of CCL2 release in 3/6 ANA, while had no effect in TFC. Pioglitazone inhibition of ANA proliferation was not associated with the effect on CCL2; NF-κB and ERK1/2 were basally activated in ANA, increased by IFN-γ+TNF-α, and pioglitazone inhibited IFN- γ+TNF-α activation. CCL2 serum levels were higher in 6 ATC patients than in 5 controls (813±345 versus 345±212, pg/mL; respectively; P<0.01, ANOVA). Conclusion: ANA produce CCL2 basally and after cytokines stimulation, with an extremely variable pattern of modulation, suggesting different types of deregulation in the chemokine modulation. Serum CCL2 is increased in ATC patients. Further studies will be necessary to evaluate if CCL2 might be used as a marker in the followup of ATC patients.

scholarly journals Ameliorative Effect of Berberine on Neonatally Induced Type 2 Diabetic Neuropathy via Modulation of BDNF, IGF-1, PPAR-γ, and AMPK Expressions

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581986244 ◽  
Author(s):  
Guangju Zhou ◽  
Mingzhu Yan ◽  
Gang Guo ◽  
Nanwei Tong
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Nitrosative Stress ◽  
Ppar Γ ◽  
Tnf Α ◽  
Protein Expressions

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations ( P < .05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated ( P < .05) these alterations. Berberine treatment significantly inhibited ( P < .05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated ( P < .05) by berberine. It also significantly downregulated ( P < .05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated ( P < .05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1β, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

PPAR-γ ligands modulate effects of LPS in stimulated rat synovial fibroblasts

2002 ◽  
Vol 282 (1) ◽  
pp. C125-C133 ◽  
Author(s):  
Marie-Agnès Simonin ◽  
Karim Bordji ◽  
Sandrine Boyault ◽  
Arnaud Bianchi ◽  
Elvire Gouze ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Constitutive Expression ◽  
Synovial Fibroblasts ◽  
Binding Activity ◽  
Inos Mrna ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α ◽  
Cox 2

This work demonstrated the constitutive expression of peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-α in rat synovial fibroblasts at both mRNA and protein levels. A decrease in PPAR-γ expression induced by 10 μg/ml lipopolysaccharide (LPS) was observed, whereas PPAR-α mRNA expression was not modified. 15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) dose-dependently decreased LPS-induced cyclooxygenase (COX)-2 (−80%) and inducible nitric oxide synthase (iNOS) mRNA expression (−80%), whereas troglitazone (10 μM) only inhibited iNOS mRNA expression (−50%). 15d-PGJ2 decreased LPS-induced interleukin (IL)-1β (−25%) and tumor necrosis factor (TNF)-α (−40%) expression. Interestingly, troglitazone strongly decreased TNF-α expression (−50%) but had no significant effect on IL-1β expression. 15d-PGJ2 was able to inhibit DNA-binding activity of both nuclear factor (NF)-κB and AP-1. Troglitazone had no effect on NF-κB activation and was shown to increase LPS-induced AP-1 activation. 15d-PGJ2 and troglitazone modulated the expression of LPS-induced iNOS, COX-2, and proinflammatory cytokines differently. Indeed, troglitazone seems to specifically target TNF-α and iNOS pathways. These results offer new insights in regard to the anti-inflammatory potential of the PPAR-γ ligands and underline different mechanisms of action of 15d-PGJ2 and troglitazone in synovial fibroblasts.

scholarly journals Effect of MEK6 Gene and Salt Treatment on Adipogenesis in MEK6 Over-expressed 3T3-L1 Cells (P21-070-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Myoungsook Lee ◽  
Songjoo Kang ◽  
Soyoung Sung ◽  
Minjee Lee ◽  
Juhee Kim ◽  
...  
Keyword(s):  
Protein Expression ◽  
Metabolic Diseases ◽  
Salt Intake ◽  
Eating Habits ◽  
Nile Red ◽  
Inflammatory Factors ◽  
O2 Consumption ◽  
Salt Treatment ◽  
Ppar Γ ◽  
Tnf Α

Abstract Objectives Both obesity and obesogenic environments(OE) to induce the fat accumulation are being the risk factors of various metabolic diseases. By 6 year-cohort study, we found that MEK6 gene and salt intake were positively related with inducing obese as part of OE factors such as lifestyle, genes, and eating habits etc. Objectives of study are to find the effects of MEK6 gene and salt treatment on adipogenesis using MEK6 over-expressed 3T3-L1 cells. Methods After transformation for MEK6 over-expressed 3T3-L1 with lipofectamine 3000 (Invitrogen, California, USA) was confirmed by PCR method, salt was treated as 50 mM in the form of NaCl without cytotoxicity (MTT assay). Cell differentiation and TG synthesis (Oil Red O; ORO & DAPI/Nile red staining), and protein expression (western blotting analysis) associated with adipogenesis genes (PPAR-γ, C/EBP-α & aP2) and adipocytokines (adiponectin & leptin) were performed. ELISA kits were used for estimating inflammatory factors such as TNF-α, IL-1β, IL-10, MCP-1, PAI-1 etc. Real-time oxygen consumption in alive cells was measured every 17 seconds for 100 minutes. (Mito-Xpress O2 consumption array kit) All analyses were performed using SAS9.1 software and p-values of <0.05 were interpreted as statistically significant. Results We confirmed the salt induced the protein expression associated with adipogenesis (PPAR-γ, C/EBP-α and aP2) in both control and MEK6 over-expressed cells. The levels of inflammatory cytokine factors (TNF-α, IL-1β, IL-10) were also increased by salt treatment in both groups. We found that obesity-linked metabolism such as lipolysis, insulin resistance, and adipocyte production were significantly higher in MEK6 over-expressed cells than them in the control. However, the leptin level did not seem to be associated with MEK6 gene. Salt also increased O2 consumption in both groups but the time to reach maximum of O2 consumption in MEK6 over-expressed cells was slower than the case of control. MEK6 might be associated with mitochondria function to control O2 consumption. Conclusions The obesity metabolism related adiopgenesis in 3T3-L1 was activated by MEK6 expression and salt treatment. These findings will contribute to a future study for finding MEK6 linked mechanisms involved in adipogenesis and for setting DRI of salt intake in obese Koreans. Funding Sources This work was funded by the Ministry of Health&Welfare, Republic of Korea grant number: HI17C0863.

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