scholarly journals Cissus Quadrangularis enhances UCP1 mRNA, indicative of white adipocyte browning and decreases central obesity in humans in a randomized trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saimai Chatree ◽  
Chantacha Sitticharoon ◽  
Pailin Maikaew ◽  
Kitchaya Pongwattanapakin ◽  
Issarawan Keadkraichaiwat ◽  
...  
Keyword(s):  
Treated Group ◽  
Dependent Manner ◽  
Hip Circumference ◽  
White Adipocyte ◽  
Ppar Γ ◽  
White Adipocytes ◽  
Cissus Quadrangularis ◽  
Baseline Values ◽  
Dose Dependent ◽  
Vehicle Treated Group

AbstractObesity is associated with the growth and expansion of adipocytes which could be decreased via several mechanisms. Cissus Quadrangularis (CQ) extract has been shown to reduce obesity in humans; however, its effect on human white adipocytes (hWA) has not been elucidated. This study aimed to investigate the effects of CQ on obesity, lipolysis, and browning of hWA. CQ treatment in obese humans significantly decreased waist circumference at week 4 and week 8 when compared with the baseline values (p < 0.05 all) and significantly decreased hip circumference at week 8 when compared with the baseline and week 4 values (p < 0.05 all). Serum leptin levels of the CQ-treated group were significantly higher at week 8 compared to baseline levels (p < 0.05). In hWA, glycerol release was reduced in the CQ-treated group when compared with the vehicle-treated group. In the browning experiment, pioglitazone, the PPAR-γ agonist, increased UCP1 mRNA when compared to vehicle (p < 0.01). Interestingly, 10, 100, and 1000 ng/ml CQ extract treatment on hWA significantly enhanced UCP1 expression in a dose-dependent manner when compared to pioglitazone treatment (p < 0.001 all). In conclusion, CQ decreased waist and hip circumferences in obese humans and enhanced UCP1 mRNA in hWA suggestive of its action via browning of hWA.

scholarly journals Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dependent Manner ◽  
Metabolic Dysfunction ◽  
Functional Interaction ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Adhesion Gpcr ◽  
Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

scholarly journals Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects

2020 ◽  
pp. 153537022096270
Author(s):  
Saimai Chatree ◽  
Chantacha Sitticharoon ◽  
Pailin Maikaew ◽  
Kitchaya Pongwattanapakin ◽  
Issarawan Keadkraichaiwat ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Human Subjects ◽  
Epigallocatechin Gallate ◽  
Metabolic Risk ◽  
Ppar Γ ◽  
White Adipocytes ◽  
Obese Subjects ◽  
Baseline Values ◽  
Obese Human

Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels ( P < 0.05), systolic blood pressure ( P < 0.05), diastolic blood pressure ( P < 0.05), and serum kisspeptin levels ( P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 ( UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes. Impact statement Obesity has become the worldwide problem that causes adverse health consequences in individuals. The effects of EGCG on decreased obesity and improved metabolic profiles are still inconclusive. This study revealed that EGCG decreased 2 metabolic risk factors including blood pressure and triglyceride in human obese subjects but had no effect on obesity reduction. This study also showed a novel finding that EGCG decreased kisspeptin levels in human obese subjects. The study in human adipocytes showed that EGCG had no effects on lipolysis nor browning of human white adipocytes. These findings might suggest that EGCG treatment ameliorated metabolic parameters but did not reduce obesity in obese humans. However, further studies are required to explore the relationship between the effect of EGCG on reduction of blood pressure and kisspeptin levels.

scholarly journals Evaluation of T-3811ME (BMS-284756), a New Des-F(6)-Quinolone, for Treatment of Meningitis Caused by Penicillin-Resistant Streptococcus pneumoniae in Rabbits

2002 ◽  
Vol 46 (6) ◽  
pp. 1760-1765 ◽  
Author(s):  
Masahiro Takahata ◽  
Hiroshi Yamada ◽  
Teiichi Morita ◽  
Shinichi Furubou ◽  
Shinzaburo Minami ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Viable Cell ◽  
Treated Group ◽  
Dependent Manner ◽  
Free Base ◽  
Time Curve ◽  
Gram Positive Bacteria ◽  
Cell Counts ◽  
Concentration Time ◽  
Dose Dependent

ABSTRACT T-3811ME (BMS-284756) is a new des-F(6)-quinolone with high levels of activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae (PRSP) strains. T-3811, the free base of T-3811ME, exhibited potent activity against 28 clinical strains of PRSP isolated clinically (MIC at which 90% of the isolates tested are inhibited, 0.0625 μg/ml). After the intravenous dosing of T-3811ME (20 mg/kg of body weight as T-3811) in rabbits with meningitis caused by PRSP, the area under the concentration-time curve (AUC) of T-3811 in cerebrospinal fluid (CSF) was 5.79 μg · h/ml and was 4.5-fold higher than that of T-3811in the CSF of rabbits without meningitis. In addition, the AUC/MIC for T-3811ME (20 mg/kg as T-3811) in CSF was 185, which was 4.3-fold higher than that for ceftriaxone (administered intravenously at 100 mg/kg). After the administration of any dose of T-3811ME (5, 10, and 20 mg/kg as T-3811), the viable cell counts in CSF decreased in a dose-dependent manner. In particular, after dosing of 20 mg/kg (as T-3811), the viable cell counts in CSF were significantly less than those in the nontreated group (P < 0.01). By histopathological evaluation, 6 h after the administration of T-3811ME (20 mg/kg as T-3811), the thickening of the cerebral meninx and the infiltration of neutrophils into the cerebral meninx were less severe in the treated group than in the nontreated group. T-3811ME (BMS-284756) may be expected to be evaluated for the management of meningitis caused by highly penicillin-resistant pneumococci.

scholarly journals Increased Expression of PPAR-γ Modulates Monocytes Into a M2-Like Phenotype in SLE Patients: An Implicative Protective Mechanism and Potential Therapeutic Strategy of Systemic Lupus Erythematosus

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Liu ◽  
Shuangyan Luo ◽  
Yi Zhan ◽  
Jiayu Wang ◽  
Rui Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treated Group ◽  
Protective Role ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Systemic Lupus ◽  
Inflammatory Reactions ◽  
Ppar Γ ◽  
Underlying Mechanisms

Systemic lupus erythematosus (SLE) is a spectrum of autoimmune disorders characterized by continuous inflammation and the production of autoantibodies. Monocytes, as precursors of dendritic cells and macrophages, are involved in the pathogenesis of SLE, particularly in the inflammatory reactions. Previous studies have proved that Pam3CSK4, as a synthetic ligand of TLR2, could stimulate monocytes to differentiated into a M2-like phenotype which presented immunosuppressive functions. However, the underlying mechanisms remain to be further studied. Here, we reported an increased expression of PPAR-γ in the CD14+ monocytes from SLE patients, particularly in the treated group of SLE patients and the group with positive anti-dsDNA antibodies. Additionally, PPAR-γ expression decreased in the SLE patients with skin lesion. Furthermore, we demonstrated that Pam3CSK4 stimulation can decrease the expression of CCR7, CD80, IL-1β, IL-6, IL-12, and NF-κB which were related to the M1-like subset of monocytes and increased the expression of ARG1 which was related to the M2-like subset through upregulated PPAR-γ expression and consequently downregulated NF-κB expression in the CD14+ monocytes in a time-dependent manner. ChIP-qPCR results further demonstrated that Pam3CSK4 pretreatment could modulate PPAR-γ expression by regulating histone modification through the inhibition of Sirt1 binding to the PPAR-γ promoter. Taken together, our study indicated a protective role of TLR2/Sirt1/PPAR-γ pathway in the pathogenesis of SLE which provided potential therapeutic strategies.

scholarly journals ASSESSMENT OF STRESS END POINTS IN VIGNA RADIATA SEEDLINGS EXPOSED TO PRE-ACTIVATED TIO2 AND TISIO4 NANOPARTICLES UNDER SOLAR RADIATION

2016 ◽  
Vol 8 (10) ◽  
pp. 198 ◽  
Author(s):  
Shweta Kaur ◽  
Anurag Maurya
Keyword(s):  
Vigna Radiata ◽  
Treated Group ◽  
Dependent Manner ◽  
End Points ◽  
Treatment Groups ◽  
Stress Biomarkers ◽  
Bulk Powder ◽  
Mechanism Of Toxicity ◽  
Dose Dependent ◽  
Assessment Of Stress

<p class="03-Address"><strong>Objective: </strong>The present study was aimed to evaluate the phototoxic effects of sunlight pre-irradiated/nonirradiated TiO<sub>2</sub>, TiSiO<sub>4</sub> nanoparticles and TiO<sub>2 </sub>bulk powder to Vigna radiata seedlings.</p><p class="03-Address"><strong>Methods</strong><strong>: </strong>Different concentrations (0.05, 0.2, 0.5 and 1.0 g/l) of nano/bulk particles were applied to the germinated seedlings for 24 h and various biochemical end points were assessed. The end points were superoxide dismutase activity, catalase activity, malondialdehyde (MDA) and proline content.</p><p class="03-Address"><strong>Results: </strong>The irradiated nano TiO<sub>2 </sub>was more phototoxic to the seedlings as compared to both the non-irradiated nano TiO<sub>2 </sub>as well as the irradiated/non-irradiated TiO<sub>2</sub> bulk powder, as revealed by the increased level of antioxidant enzymes activity in irradiated TiO<sub>2</sub> nanoparticles treated group. Toxicity in nano TiO<sub>2</sub> group was more confined to the lowest concentration (0.05 g/l). Proline, a well-recognized stress biomarker, was found to increase in all the irradiated as well as the non-irradiated groups in a dose dependent manner (0.20 to 1.0 g/l), offering a different mechanism of toxicity from that of antioxidative enzymes. TiSiO<sub>4</sub> nanoparticles were not found to be phototoxic significantly under either exposure conditions.</p><p class="03-Address"><strong>Conclusion: </strong>The seedlings of the three treatment groups responded variably to the stress biomarkers, indicating that the mode of action of the nanoparticles to the plant was different from that of the bulk particles in irradiated and non-irradiated conditions and was governed by more than a single factor.</p>

scholarly journals Antimalarial Activity of Kaempferol and Its Combination with Chloroquine in Plasmodium berghei Infection in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Voravuth Somsak ◽  
Awatsada Damkaew ◽  
Pinanong Onrak
Keyword(s):  
Plasmodium Berghei ◽  
Chronic Toxicity ◽  
Antimalarial Activity ◽  
Chronic Administration ◽  
Treated Group ◽  
Effective Vaccine ◽  
Dependent Manner ◽  
Standard Procedures ◽  
Dose Dependent

The search for new antimalarial drugs has become an urgent requirement due to resistance to the available drugs and the lack of an effective vaccine. In this respect, the present study aimed to evaluate the antimalarial activity of kaempferol against Plasmodium berghei infection in mice as an in vivo model. Chronic toxicity and antimalarial activities of kaempferol alone and in combination with chloroquine were investigated in P. berghei ANKA infected ICR mice using standard procedures. The results showed that chronic administration of 2,000 mg/kg of kaempferol resulted in no overt signs of toxicity as well as no hepatotoxicity, nephrotoxicity, or hematotoxicity. Interestingly, kaempferol exerted significant (P < 0.05) chemosuppressive, chemoprophylactic, and curative activities in a dose-dependent manner. The highest antimalarial activity was found at a dose of 20 mg/kg which resulted in a significantly (P < 0.05) prolonged survival of infected mice. Moreover, combination treatment of chloroquine and kaempferol also presented significant (P < 0.05) antimalarial effects, although the effects were not significantly different from the chloroquine treated group. From the results of the present study, it can be concluded that kaempferol possesses acceptable antimalarial activities. However, further investigation should be undertaken on the mechanism responsible for the observed antimalarial activity.

scholarly journals Morusin Functions as a Lipogenesis Inhibitor as Well as a Lipolysis Stimulator in Differentiated 3T3-L1 and Primary Adipocytes

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2004 ◽  
Author(s):  
Mi Rim Lee ◽  
Ji Eun Kim ◽  
Jun Young Choi ◽  
Jin Ju Park ◽  
Hye Ryeong Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Insulin Receptor ◽  
Adipogenic Differentiation ◽  
Treated Group ◽  
G1 Arrest ◽  
Dependent Manner ◽  
Glycerol Release ◽  
Insulin Receptor Signaling ◽  
Dose Dependent

Conflicting results for morusin activity during adipogenic differentiation are reported in 3T3-L1 adipocytes and cancer cells. To elucidate the influence of morusin on fat metabolism, their anti-obesity effects and molecular mechanism were investigated in 3T3-L1 cells and primary adipocytes. Morusin at a dose of less than 20 µM does not induce any significant change in the viability of 3T3-L1 adipocytes. The accumulation of intracellular lipid droplets in 3T3-L1 adipocytes stimulated with 0.5 mM 3-isobutyl-1-methylxanthine, 1 µM dexamethasone, 10 µg/mL insulin in DMEM containing 10% FBS (MDI)-significantly reduces in a dose-dependent manner after morusin treatment. The phosphorylation level of members in the MAP kinase signaling pathway under the insulin receptor downstream also decrease significantly in the MDI + morusin-treated group compared to MDI + vehicle-treated group. Also, the expression of adipogenic transcription factors (PPARγ and C/EBPα) and lipogenic proteins (aP2 and FAS) are significantly attenuated by exposure to the compound in MDI-stimulated 3T3-L1 adipocytes. Furthermore, the decrease in the G0/G1 arrest of cell cycle after culturing in MDI medium was dramatically recovered after co-culturing in MDI + 20 µM morusin. Moreover, morusin treatment induces glycerol release in the primary adipocytes of SD rats and enhances lipolytic protein expression (HSL, ATGL, and perilipin) in differentiated 3T3-L1 adipocytes. Overall, the results of the present study provide strong evidence that morusin inhibits adipogenesis by regulating the insulin receptor signaling, cell cycle and adipogenic protein expression as well as stimulating lipolysis by enhancing glycerol release and lipolytic proteins expression.

Madhuca longifolia embedded silver nanoparticles attenuates diethylnitrosamine (DEN) -induced renal cancer via regulating oxidative stress

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepika Singh ◽  
Ekta Yadav ◽  
Vikas Kumar ◽  
Amita Verma
Keyword(s):  
Silver Nanoparticles ◽  
Renal Cancer ◽  
Safety Concern ◽  
Treated Group ◽  
Dependent Manner ◽  
Protective Effects ◽  
Antineoplastic Effect ◽  
Tnf Α ◽  
Madhuca Longifolia ◽  
Dose Dependent

Objective: Madhuca longifolia has been used for the treatment of renal cancer. Therefore, the current study describes the protective effects of biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia aqueous leaves extract against diethylnitrosamine (DEN) induced renal cell carcinoma (RCC) in rats. Methods: Animals were categorized into five groups and treated with doses of silver nanoparticles for 16 weeks. Antineoplastic effect in renal cancer was dose dependent to control the macroscopical variations when compared to DEN induced group. Significant changes were observed in biochemical parameters and dose graded improvement in the level of antioxidants parameters were accountable for its protective nature. Result: Silver nanoparticles in dose dependent manner was effective to modify the raised levels of pro-inflammatory cytokines and inflammatory mediators during renal cancer. Alteration in renal histopathology were also detected in the silver nanoparticles treated group, which show its safety concern. Biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia can convey significant chemo-protective effect against renal cancer by suppressing the IL-6, TNF-α and IL-1β by nuclear factor-kappa B (NF-κB) pathway. Conclusion: Our outcomes implicates that biofabricated MLAgNPs exhibited a chemoprotective potential in the prevention and intervention of RCC.

Primary chemoprevention of endometrial hyperplasia with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone in the PTEN heterozygote murine model

2008 ◽  
Vol 18 (2) ◽  
pp. 329-338 ◽  
Author(s):  
W. Wu ◽  
J. Celestino ◽  
M. R. Milam ◽  
K. M. Schmeler ◽  
R. R. Broaddus ◽  
...  
Keyword(s):  
Cell Lines ◽  
Murine Model ◽  
Endometrial Hyperplasia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Dose Dependent

PTEN mutations have been implicated in the development of endometrial hyperplasia and subsequent cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have demonstrated antineoplastic and chemopreventive effects. The purpose of this study was to evaluate the effects of the PPAR-γ agonist rosiglitazone on both PTEN wild type and PTEN null cell lines and in the PTEN heterozygote(+/−) murine model. Hec-1-A (PTEN wild type) and Ishikawa (PTEN null) cells were treated with rosiglitazone. Thirty-five female PTEN+/− mice were genotyped and placed into one of four groups for treatment for 18 weeks: A) PTEN wild type with 4 mg/kg rosiglitazone, B) PTEN+/− mice with vehicle, C) PTEN+/− mice with 4 mg/kg rosiglitazone, and D) PTEN+/− mice with 8 mg/kg rosiglitazone. Proliferation and apoptosis were measured by bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of DNA fragmentation sites assay. Rosiglitazone caused cell growth inhibition in both Hec-1-A and Ishikawa in a dose-dependent manner (P< 0.02 and P< 0.03, respectively). Rosiglitazone also induced apoptosis in both Hec-1-A (P< .001) and Ishikawa (P< .001) cells in a dose-dependent manner. In the murine model, rosiglitazone decreased proliferation of the endometrial hyperplastic lesions (B vs C; 39.7% vs 9.3% and B vs D; 39.7% vs 4.2%; P< 0.0001) and increased apoptosis of glandular endometrial epithelial cells (B vs C; 2.8% vs 22.4%; P< 0.0001 and B vs D; 2.8% vs 30.2%; P= 0.003). PPAR-γ agonist rosiglitazone inhibits proliferation and induces apoptosis in both PTEN intact and PTEN null cancer cell lines and in hyperplastic endometrial lesions in the PTEN+/− murine model.

Discovery of Glabridin as Potent Inhibitor of Epidermal Growth Factor Receptor in SK-BR-3 Cell

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 113-125
Author(s):  
Kun Zhu ◽  
Kang Li ◽  
Haonan Wang ◽  
Li Kang ◽  
Chengxue Dang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Treated Group ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Epidermal Growth ◽  
Dose Dependent

The breast cancer is the leading cause of death in women. Therefore, objective of the present study was to examine the antibreast cancer effect of glabridin (GBN) and to evaluate its mechanism of action. In this study, we have demonstrated that GBN causes reduction of cellular viability of human breast cancer SK-BR-3 in MTT assay. Results from Hoechst 33342 and propidium iodide staining assay suggested that GBN causes significant enhancement in the apoptosis. At the molecular level, in western blot analysis, GBN causes significant increase in c-PARP and c-caspases 3, 8, and 9 concentrations in a dose-dependent manner in breast cancer cells. The GBN further showed reduced level of p-epidermal growth factor receptor, p-AKT, p-ERK1/2, and cyclin D1 as the concentration rose in treated cells. Subsequent to this, GBN showed beneficial effect in 7,12-dimethylbenz[a]anthracene-induced breast cancer in experimental mice as confirmed by increase in body weight, reduction in tumor volume, oxidative stress, and dose-dependent restoration of all tested enzymes (phase I and II) in the treated group. GBN may, thus, play a protective role as an antibreast cancer drug for the prevention of breast cancer.

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