scholarly journals (+)-Catechin & Proanthocyanidin Fraction of Uncaria gambir Roxb. Improve Adipocytes Differentiation & Glucose Uptake of 3T3-L1 Cells Via Sirtuin-1, Peroxisome Proliferator-Activated Receptor γ (PPAR γ), Glucose Transporter Type 4 (GLUT-4) Expressions

2020 ◽  
Vol 10 (4) ◽  
pp. 602-609
Author(s):  
Silvy Arundita ◽  
Friardi Ismed ◽  
Rauza Sukma Rita ◽  
Deddi Prima Putra
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Specific Inhibitor ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glut 4 ◽  
Ppar Γ ◽  
Uptake Activity ◽  
Glucose Transporter Type 4

Purpose : To improve adipocytes differentiation & glucose uptake activity of 3T3-L1 cells through sirtuin-1, peroxisome proliferator-activated receptor γ (PPAR γ), glucose transporter type 4 (GLUT-4) of (+)-catechin & proanthocyanidin fraction Uncaria gambir Roxb. Methods: Adipocytes differentiation activity of (+)-Catechin of Uncaria gambir Roxb. was determined by oil red O staining method & glucose uptake activity was determined by measuring 2-deoxyglucose uptake on 3T3-L1 cells. The ability of (+) - catechin as an activator of sirtuin-1 was assessed by administration of (+) - catechin with the presence of a specific inhibitor of sirtuin-1, nicotinamide. Metformin 1 mM & 5 mM were used as positive control. Sirtuin-1, PPAR γ & GLUT-4 expressions were determined by RT-PCR. Results: (+)-Catechin & proanthocyanidin fraction of Uncaria gambir Roxb. were found to increase adipocyte differentiation & glucose uptake by increasing activity of sirtuin-1 as well as metformin (P≤0.05). PPAR γ, GLUT-4 and sirtuin-1 expressions were known to be responsible for this activities. Conclusion: These results indicate that (+)–catechin & proanthocyanidin fraction of Uncaria gambir Roxb. could be utilized as a renewable bioresource to develop potential antidiabetic and antiobesity agents.

scholarly journals AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle

2019 ◽  
Vol 316 (5) ◽  
pp. E931-E939 ◽  
Author(s):  
Jin-Ho Koh ◽  
Chad R. Hancock ◽  
Dong-Ho Han ◽  
John O. Holloszy ◽  
K. Sreekumaran Nair ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glut4 Expression ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise ◽  
Glucose Transporter Type 4

The objective of this study is to determine whether AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), or peroxisome proliferator-activated receptor β (PPARβ) can independently mediate the increase of glucose transporter type 4 (GLUT4) expression that occurs in response to exercise training. We found that PPARβ can regulate GLUT4 expression without PGC-1α. We also found AMPK and PPARβ are important for maintaining normal physiological levels of GLUT4 protein in the sedentary condition as well following exercise training. However, AMPK and PPARβ are not essential for the increase in GLUT4 protein expression that occurs in response to exercise training. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Furthermore, exercise training increases the cooperation of AMPK and PPARβ to regulate glucose uptake. In conclusion, cooperation between AMPK and PPARβ via NRF-1/MEF2A pathway enhances the exercise training mediated adaptive increase in GLUT4 expression and subsequent glucose uptake in skeletal muscle.

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.

Triterpenoids from Hibiscus sabdariffa L. with PPARδ/γ Dual Agonist Action: In Vivo, In Vitro and In Silico Studies

Planta Medica ◽  
2019 ◽  
Vol 85 (05) ◽  
pp. 412-423 ◽  
Author(s):  
Abraham Giacoman-Martínez ◽  
Francisco Alarcón-Aguilar ◽  
Alejandro Zamilpa ◽  
Sergio Hidalgo-Figueroa ◽  
Gabriel Navarrete-Vázquez ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Messenger Ribonucleic Acid ◽  
Transporter Protein ◽  
Agonist Action ◽  
Fatty Acid Transporter ◽  
Peroxisome Proliferator Activated Receptors ◽  
Glucose Transporter Type 4 ◽  
Dual Agonist

Abstract Hibiscus sabdariffa is a medicinal plant consumed as a diuretic and anti-obesity remedy. Several pharmacological studies have shown its beneficial effects in metabolism. Peroxisome proliferator-activated receptors δ and γ may play a role in the actions of H. sabdariffa. These nuclear receptors regulate lipid and glucose metabolism and are therapeutic targets for type 2 diabetes. This research aimed to perform a phytochemical study guided by a bioassay from H. sabdariffa to identify compounds with peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ agonist activity, supported by messenger ribonucleic acid expression, molecular docking, lipid accumulation, and an antihyperglycemic effect. An oral glucose tolerance test in mice with the aqueous extract of H. sabdariffa and the dichloromethane extract of H. sabdariffa was performed. The dichloromethane extract of H. sabdariffa exhibited an antihyperglycemic effect. The dichloromethane extract of H. sabdariffa was fractioned, and four fractions were evaluated in 3T3-L1 adipocytes on peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 messenger ribonucleic acid expression. Fraction F3 exhibited peroxisome proliferator-activated receptor δ/γ dual agonist activity, and a further fractionation yielded two subfractions, F3-1 and F3-2, which also increased peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ expression. Subfractions were analyzed by GC/MS. The main compounds identified in F3-1 were linoleic acid, oleic acid, and palmitic acid, while in F3-2, the main compounds identified were α-amyrin and lupeol. These molecules were subjected to molecular docking analysis. α-Amyrin and lupeol showed the highest affinity. Moreover, both produced an increase in peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 expression. Additionally, α-amyrin and lupeol decreased lipid accumulation in 3T3-L1 adipocytes and blood glucose in mice. Until now, α-amyrin and lupeol have not been reported with activity on peroxisome proliferator-activated receptors. This study provides evidence that α-amyrin and lupeol possess antidiabetic effects through a peroxisome proliferator-activated receptor δ/γ dual agonist action.

scholarly journals Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2023 ◽  
Author(s):  
Junnan Ma ◽  
Seok Yong Kang ◽  
Xianglong Meng ◽  
An Na Kang ◽  
Jong Hun Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Water Extract ◽  
Sirtuin 1 ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dioscorea Batatas

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

Suppression of PPAR-γ attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes

2007 ◽  
Vol 293 (1) ◽  
pp. E219-E227 ◽  
Author(s):  
Wei Liao ◽  
M. T. Audrey Nguyen ◽  
Takeshi Yoshizaki ◽  
Svetlana Favelyukis ◽  
David Patsouris ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling ◽  
Adipocyte Differentiation ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α ◽  
Interfering Rna

Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays a critical role in regulating insulin sensitivity and glucose homeostasis. In this study, we identified highly efficient small interfering RNA (siRNA) sequences and used lentiviral short hairpin RNA and electroporation of siRNAs to deplete PPAR-γ from 3T3-L1 adipocytes to elucidate its role in adipogenesis and insulin signaling. We show that PPAR-γ knockdown prevented adipocyte differentiation but was not required for maintenance of the adipocyte differentiation state after the cells had undergone adipogenesis. We further demonstrate that PPAR-γ suppression reduced insulin-stimulated glucose uptake without affecting the early insulin signaling steps in the adipocytes. Using dual siRNA strategies, we show that this effect of PPAR-γ deletion was mediated by both GLUT4 and GLUT1. Interestingly, PPAR-γ-depleted cells displayed enhanced inflammatory responses to TNF-α stimulation, consistent with a chronic anti-inflammatory effect of endogenous PPAR-γ. In summary, 1) PPAR-γ is essential for the process of adipocyte differentiation but is less necessary for maintenance of the differentiated state, 2) PPAR-γ supports normal insulin-stimulated glucose transport, and 3) endogenous PPAR-γ may play a role in suppression of the inflammatory pathway in 3T3-L1 cells.

scholarly journals Formononetin inhibits lipopolysaccharide-induced release of high mobility group box 1 by upregulating SIRT1 in a PPARδ-dependent manner

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4208 ◽  
Author(s):  
Jung Seok Hwang ◽  
Eun Sil Kang ◽  
Sung Gu Han ◽  
Dae-Seog Lim ◽  
Kyung Shin Paek ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
High Mobility ◽  
Inhibitory Effect ◽  
Sirtuin 1 ◽  
High Mobility Group ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sirt1 Expression

Background The release of high mobility group box 1 (HMGB1) induced by inflammatory signals acts as a cellular alarmin to trigger a chain of inflammatory responses. Although the inflammatory actions of HMGB1 are well studied, less is known about the therapeutic agents that can impede its release. This study investigated whether the isoflavonoid formononetin can modulate HMGB1 release in cellular inflammatory responses. Methods RAW264.7 murine macrophages were exposed to lipopolysaccharide (LPS) in the presence or absence of formononetin. The levels of HMGB1 release, sirtuin 1 (SIRT1) expression, and HMGB1 acetylation were analyzed by immunoblotting and real-time polymerase chain reaction. The effects of resveratrol and sirtinol, an activator and inhibitor of SIRT1, respectively, on LPS-induced HMGB1 release were also evaluated. Results Formononetin modulated cellular inflammatory responses by suppressing the release of HMGB1 by macrophages exposed to LPS. In RAW264.7 cells, formononetin significantly attenuated LPS-induced release of HMGB1 into the extracellular environment, which was accompanied by a reduction in its translocation from the nucleus to the cytoplasm. In addition, formononetin significantly induced mRNA and protein expression of SIRT1 in a peroxisome proliferator-activated receptor δ (PPARδ)-dependent manner. These effects of formononetin were dramatically attenuated in cells treated with small interfering RNA (siRNA) against PPARδ or with GSK0660, a specific inhibitor of PPARδ, indicating that PPARδ is involved in formononetin-mediated SIRT1 expression. In line with these effects, formononetin-mediated inhibition of HMGB1 release in LPS-treated cells was reversed by treatment with SIRT1-targeting siRNA or sirtinol, a SIRT1 inhibitor. By contrast, resveratrol, a SIRT1 activator, further potentiated the inhibitory effect of formononetin on LPS-induced HMGB1 release, revealing a possible mechanism by which formononetin regulates HMGB1 release through SIRT1. Furthermore, modulation of SIRT1 expression by transfection of SIRT1- or PPARδ-targeting siRNA significantly counteracted the inhibitory effects of formononetin on LPS-induced HMGB1 acetylation, which was responsible for HMGB1 release. Discussion This study shows for the first time that formononetin inhibits HMGB1 release by decreasing HMGB1 acetylation via upregulating SIRT1 in a PPARδ-dependent manner. Formononetin consequently exhibits anti-inflammatory activity. Identification of agents, such as formononetin, which can block HMGB1 release, may help to treat inflammation-related disorders.

In vitro Studies on Antidiabetic Potential of New Dosage Forms of AYUSH 82

2017 ◽  
Vol 2 (1) ◽  
pp. 1-9
Author(s):  
M Setia ◽  
K Meena ◽  
A Madaan ◽  
Kartar S Dhiman ◽  
JLN Sastry
Keyword(s):  
Glucose Uptake ◽  
Dosage Forms ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Test Items ◽  
Ppar Γ ◽  
Central Council ◽  
Insulin Dependent

ABSTRACT AYUSH 82 powder is an Ayurvedic antidiabetic formulation developed by the Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of AYUSH, Government of India. It comprises ingredients traditionally used for their beneficial effect in diabetes (Prameha/Madhumeha). The hypoglycemic effects of AYUSH 82 powder have been reported in diabetic subjects. In the current study, the antidiabetic potential of AYUSH 82 powder along with its two new dosage forms – AYUSH 82 mixture extract and AYUSH 82 compound extract- was investigated in vitro for elucidating mechanism of their action by possible α-amylase inhibitory property, insulin-dependent glucose uptake in skeletal muscle cell line (C2C12 myotubes), and effect on peroxisome proliferator-activated receptor gamma (PPAR-γ) activity. All the three dosage forms of AYUSH 82 – powder, mixture extract, and compound extract – exhibited inhibition of α-amylase activity. AYUSH 82 mixture extract, however, demonstrated highest extent of inhibition in both methanolic (87.4%) and aqueous (48.2%) format. All the three dosage forms of AYUSH 82 also demonstrated an increase in insulin-dependent glucose uptake in C2C12 myotubes as compared with control. However, none of the test items (TIs) exhibited activation of PPAR-γ expression in tested ranges, indicating that antidiabetic potential of TIs may not be mediated via PPAR-γ activation. Results indicated that the new dosage forms of AYUSH 82 (mixture extract and compound extract) may be useful for making new dosage forms of AYUSH 82 as tablets/capsule, etc. How to cite this article Setia M, Meena K, Madaan A, Srikanth N, Dhiman KS, Sastry JLN. In vitro Studies on Antidiabetic Potential of New Dosage Forms of AYUSH 82. J Drug Res Ayurvedic Sci 2017;2(1):1-9.

scholarly journals Characteristics and Glucose Uptake Promoting Effect of Chrysin-Loaded Phytosomes Prepared with Different Phospholipid Matrices

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2549 ◽  
Author(s):  
Seong-Min Kim ◽  
Jae-In Jung ◽  
Changhoon Chai ◽  
Jee-Young Imm
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Molar Ratio ◽  
Peroxisome Proliferator ◽  
Promoting Effect ◽  
Uniform Size ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Complexation ◽  
Average Size ◽  
Molecular Bonding

Chrysin-loaded phytosomes (CP) were prepared using either soya phosphatidylcholine (SPC) or egg phospholipid (EPL) by the solvent evaporation method. Different phospholipid matrices resulted in significant differences in size, mechanical property and solubility of the CP. The most stable CP was obtained with EPL at a molar ratio of 1:3 (chrysin: EPL, CEP-1:3). CEP-1:3 displayed an average size of 117 nm with uniform size distribution (polydispersity index: 0.30) and zeta potential of −31 mV. A significantly greater elastic modulus of CEP-1:3 (2.7-fold) indicated tighter packing and strong molecular bonding than those of CP prepared with SPC (CSP-1:3). X-ray diffraction and Fourier transform infrared spectroscopic analysis of CEP-1:3 confirmed molecular complexation. CEP-1:3 displayed a greater glucose uptake promoting effect than free chrysin and CSP-1:3 in muscle cells by stimulating gene expression of peroxisome proliferator-activated receptor γ and glucose transporter type 4. The results of the present study suggest that the phospholipid matrix used for the preparation of phytosomes critically influences their performance.

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