scholarly journals Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2282
Author(s):  
Norman Balcazar ◽  
Laura I. Betancur ◽  
Diana L. Muñoz ◽  
Frankly J. Cabrera ◽  
Adriana Castaño ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Ursolic Acid ◽  
Biological Activities ◽  
In Vitro Study ◽  
Strong Relationship ◽  
Eucalyptus Tereticornis ◽  
Insulin Resistant ◽  
Expression Of Genes ◽  
Acid Lactone

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.

scholarly journals RELATIVE POTENCY OF ANTI-DIABETIC COSTUS SPECIOSUSPLANT EXTRACT IN MOUSE FIBROBLAST CELL LINE

2016 ◽  
Vol 4 (3) ◽  
pp. 99-107
Author(s):  
Bindu ◽  
Rama Bhat ◽  
Girish ◽  
Krishna Prasad
Keyword(s):  
Glucose Uptake ◽  
Biological Activities ◽  
Glycogen Synthesis ◽  
In Vitro Study ◽  
Significant Inhibition ◽  
Mouse Fibroblast ◽  
Relative Potency ◽  
Major Pathway ◽  
Chemical Structures

Plant-derived compounds have been used clinically to treat type 2 diabetes for many years as they also exert additional beneficial effects on various other disorders. PI3K pathway is the major pathway activated by insulin receptor (IR). It induces glucose uptake, glycogen synthesis, protein synthesis, cell growth and differentiation. Hence metabolic assay was employed to assess glucose uptake based on the property of 3T3-L 1 cells to differentiate into adipocytes which can take up the glucose in medium due to the effect of insulin or insulin like molecules. The results of the current study showed that plants extract probably exerts its anti-diabetic properties by stimulating glucose uptake in adipocytes with significant inhibition of adipogenesis demonstrating reliable relative potency in comparision to the commercial insulin.  The ability of existing therapies to target various aspects of the insulin resistance syndrome induces other metabolic abnormalities, chiefly those involved in lipid metabolism. In this preliminary in-vitro study Costusspeciosus plant extract demonstrated to have significant relative potency in comparison to commercial Insulin which can be exploited to treat diabetes using natural herbal extracts Current study leads researchers to elucidate the chemical structures, isolate active ingrediatents in the crude extract for such biological activities in reference to commercial and recombinant insulins.

scholarly journals Myocardial Glucose Clearance by Aspalathin Treatment in Young, Mature, and Obese Insulin-Resistant Rats

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 75-82 ◽  
Author(s):  
Sybrand Smit ◽  
Rabia Johnson ◽  
Mignon Van Vuuren ◽  
Barbara Huisamen
Keyword(s):  
Glucose Uptake ◽  
South African ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
In Vitro Study ◽  
Trypan Blue Exclusion ◽  
Insulin Resistant ◽  
Male Wistar Rats ◽  
High Caloric Diet

AbstractRooibos, an indigenous South African plant ingested as herbal tea, is well known for its antioxidant effects. This in vitro study investigated aspalathin (C21H24O11), a dihydrochalcone unique to rooibos, for hypoglycemic effects in the context of age- and obesity-induced insulin resistance and the mechanisms involved. Male Wistar rats were allocated into three groups: 16 – 30 weeks feeding with either standard rat chow or a high-caloric diet, or 6 – 10 weeks feeding with standard rat chow. Ventricular cardiomyocytes were isolated by collagenase perfusion digestion, and glucose uptake was determined by 2-[3H]-deoxyglucose accumulation. Viability was tested by trypan blue exclusion or propidium iodide staining. The high-caloric diet significantly increased body weight gain (508.5 ± 50.0 vs. 417.3 ± 40.0 g), visceral adiposity (42.30 ± 10.1 vs. 21.75 ± 7.0 g), and fasting blood glucose (5.7 ± 0.4 vs. 4.7 ± 0.1 mM). Aspalathin (10 µM for 90 min) induced 2-[3H]-deoxyglucose uptake in young cardiomyocytes (37.2 ± 13.9 vs. 25.7 ± 2.5 pmol 2-[3H]-deoxyglucose/mg protein) and enhanced insulin-mediated 2-[3H]-deoxyglucose uptake in control cells (32.4 ± 6.4 vs. 23.5 ± 10.0 pmol 2-[3H]-deoxyglucose/mg protein), but failed to induce 2-[3H]-deoxyglucose uptake in high-caloric diet cells. Aspalathin induced glucose uptake in insulin-sensitive cardiomyocytes from young and aged rats, but not in high-caloric diet animals and enhanced the actions of insulin through a PI3K-dependent mechanism, resulting in an additive response.

scholarly journals IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis

2017 ◽  
Vol 10 (4) ◽  
pp. 216 ◽  
Author(s):  
Dian Ayu Eka Pitaloka ◽  
Elin Yulinah Sukandar
Keyword(s):  
Ursolic Acid ◽  
Drug Combination ◽  
Resistant Strain ◽  
Inhibitory Concentration ◽  
In Vitro Study ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Minimum Concentration ◽  
Different Strains

Objective: The resurgence of tuberculosis (TB) caused by Mycobacterium TB (MTB) is associated with the rapid spread of multidrug-resistant,therefore, the development of new antimycobacterial agents is necessary. The aim of this study was to evaluate the antimycobacterial activity ofursolic acid (UA) when it using alone and combination with TB drugs.Methods: MTB H37Rv strain, streptomycin-rifampicin resistant strain, and isoniazid-ethambutol resistant strain were evaluated by susceptibility testusing a serial number of UA (25-150 µg/mL). Minimum inhibitory concentration (MIC) was read as minimum concentration of drugs that completelyinhibit visible growth of organism. Activities of drug combination of UA with TB drug were determined in Lowenstein-Jensen media by calculatingthe fractional inhibitory concentration index.Results: The results showed that MIC of UA was 50 µg/mL against three different strains of MTB. The combination of UA and TB drugs displayedsynergistic interaction, and no antagonism result from the combination was observed for strains of MTB.Conclusion: These results indicate that UA may serve as a promising lead compound for future antimycobacterial drug development.Keywords: Ursolic acid, Tuberculosis, Drug combination, Susceptibility test

scholarly journals In Vitro study for hesperidin nanoparticles effect on phagocytic activity against Staphylococcus aureus

2018 ◽  
Vol 12 (2) ◽  
pp. 36-39
Author(s):  
Saja Ali ◽  
Ghassan Sulaiman ◽  
Mohammed M. Al-Halbosiy
Keyword(s):  
Biological Activities ◽  
In Vitro Study ◽  
Particle Size Analysis ◽  
Poloxamer 407 ◽  
Size Analysis ◽  
Therapeutic Effects ◽  
X Ray Diffraction ◽  
Setup Cost ◽  
Phagocytosis Index

       Hesperidin is one of the flavonoids from citrus peels and it recognized to possess various biological activities such as, anti-inflammatory, anti-carcinogenic, antioxidant and antimicrobial potentials. The present investigation studies the immunological adjuvant influence of hesperidin nanoparticles. Hesperidin nanoparticles were prepared by nano-precipitation technique by using Poly (D, L-lactic-co-glycolic acid) (PLGA) polymer and Poloxamer 407 was used as a stabilizer. This method was used because of their advantage of low setup cost and simplicity. Hesperidin nanoparticles were characterized by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and particle size analysis (PSA) analytical methods. The effect of hesperidin nanoparticles was higher than the effect of pure hesperidin, and there was an obvious increase in phagocytosis index (PI 82%) of hesperidin nanoparticles when compared with pure hesperidin (PI 56%) and in comparison with the control samples (PI 22%). In conclusion we need further studies about if nano-hesperidin has therapeutic effects.

scholarly journals Anti-Diabetic Activity of 2,3,6-Tribromo-4,5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula through PTP1B Downregulation and α-Glucosidase Inhibition

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 166 ◽  
Author(s):  
Pradeep Paudel ◽  
Su Seong ◽  
Hye Park ◽  
Hyun Jung ◽  
Jae Choi
Keyword(s):  
Glucose Uptake ◽  
Methyl Ether ◽  
In Silico ◽  
Hepg2 Cells ◽  
Halogen Bond ◽  
Biological Activities ◽  
Tyrosine Phosphatase ◽  
Docking Simulations ◽  
Insulin Resistant ◽  
Ring Number

The marine alga, Symphyocladia latiuscula (Harvey) Yamada, is a good source of bromophenols with numerous biological activities. This study aims to characterize the anti-diabetic potential of 2,3,6-tribromo-4,5-dihydroxybenzyl derivatives isolated from S. latiuscula via their inhibition of tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Additionally, this study uses in silico modeling and glucose uptake potential analysis in insulin-resistant (IR) HepG2 cells to reveal the mechanism of anti-diabetic activity. This bioassay-guided isolation led to the discovery of three potent bromophenols that act against PTP1B and α-glucosidase: 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). All compounds inhibited the target enzymes by 50% at concentrations below 10 μM. The activity of 1 and 2 was comparable to ursolic acid (IC50; 8.66 ± 0.82 μM); however, 3 was more potent (IC50; 5.29 ± 0.08 μM) against PTP1B. Interestingly, the activity of 1–3 against α-glucosidase was 30–110 times higher than acarbose (IC50; 212.66 ± 0.35 μM). Again, 3 was the most potent α-glucosidase inhibitor (IC50; 1.92 ± 0.02 μM). Similarly, 1–3 showed concentration-dependent glucose uptake in insulin-resistant HepG2 cells and downregulated PTP1B expression. Enzyme kinetics revealed different modes of inhibition. In silico molecular docking simulations demonstrated the importance of the 7–OH group for H-bond formation and bromine/phenyl ring number for halogen-bond interactions. These results suggest that bromophenols from S. latiuscula, especially highly brominated 3, are inhibitors of PTP1B and α-glucosidase, enhance insulin sensitivity and glucose uptake, and may represent a novel class of anti-diabetic drugs.

scholarly journals G-quadruplex ligands mediate downregulation of DUX4 expression

2020 ◽  
Vol 48 (8) ◽  
pp. 4179-4194 ◽  
Author(s):  
Lukasz Ciszewski ◽  
Ngoc Lu-Nguyen ◽  
Alex Slater ◽  
Andrew Brennan ◽  
Huw E L Williams ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
In Vitro Study ◽  
Bioinformatic Analysis ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Nuclear Magnetic Resonance Analysis ◽  
Therapeutic Effects ◽  
Muscle Fibrosis ◽  
Expression Of Genes ◽  
Genetic Structures

Abstract Abnormal DUX4 expression in skeletal muscles plays a key role in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, although the molecular mechanisms regulating DUX4 expression are not fully defined. Using bioinformatic analysis of the genomic DUX4 locus, we have identified a number of putative G-quadruplexes (GQs) forming sequences. Their presence was confirmed in synthetic oligonucleotiode sequences derived from the enhancer, promoter and transcript of DUX4 through circular dichroism and nuclear magnetic resonance analysis. We further examined the binding affinity of a naturally occurring GQ stabilizing compound, berberine, to these non-canonical genetic structures using UV–Vis and fluorescence spectroscopy. Subsequent in vitro study in FSHD patient myoblasts indicated that berberine treatment reduced DUX4 expression and also expression of genes normally switched on by DUX4. Further investigation in a mouse model overexpressing exogenous DUX4 confirmed the therapeutic effects of berberine in downregulating DUX4 protein expression, inhibiting muscle fibrosis, and consequently rescuing muscle function. Our data demonstrate for the first time that GQs are present in the DUX4 locus and that the GQ interactive ligand reduces DUX4 expression suggesting potential role of GQs in FSHD pathogenesis. Our work provides the basis of a novel therapeutic strategy for the treatment of FSHD.

A novel small molecule A2A adenosine receptor agonist, indirubin-3′-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes

2019 ◽  
Vol 476 (16) ◽  
pp. 2371-2391 ◽  
Author(s):  
Saynaz A. Choudhary ◽  
Nikita Bora ◽  
Dipanjan Banerjee ◽  
Leena Arora ◽  
Anindhya Sundar Das ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adenosine Receptor ◽  
In Vitro Study ◽  
A2a Adenosine Receptor ◽  
Insulin Resistant ◽  
Adenosine Receptor Agonist ◽  
Inflammatory State

Abstract Saturated free fatty acid-induced adipocyte inflammation plays a pivotal role in implementing insulin resistance and type 2 diabetes. Recent reports suggest A2A adenosine receptor (A2AAR) could be an attractive choice to counteract adipocyte inflammation and insulin resistance. Thus, an effective A2AAR agonist devoid of any toxicity is highly appealing. Here, we report that indirubin-3′-monoxime (I3M), a derivative of the bisindole alkaloid indirubin, efficiently binds and activates A2AAR which leads to the attenuation of lipid-induced adipocyte inflammation and insulin resistance. Using a combination of in silico virtual screening of potential anti-diabetic candidates and in vitro study on insulin-resistant model of 3T3-L1 adipocytes, we determined I3M through A2AAR activation markedly prevents lipid-induced impairment of the insulin signaling pathway in adipocytes without any toxic effects. While I3M restrains lipid-induced adipocyte inflammation by inhibiting NF-κB dependent pro-inflammatory cytokines expression, it also augments cAMP-mediated CREB activation and anti-inflammatory state in adipocytes. However, these attributes were compromised when cells were pretreated with the A2AAR antagonist, SCH 58261 or siRNA mediated knockdown of A2AAR. I3M, therefore, could be a valuable option to intervene adipocyte inflammation and thus showing promise for the management of insulin resistance and type 2 diabetes.

Sign in / Sign up

Export Citation Format

Share Document