PTP-1b

Three new germacrane-type sesquiterpene lactones (1-3) were isolated alongside seven known related congeners (4-10) from the leaves of Eupatorium chinense L. (Compositae). The planar structures of 1-3 were elucidated by their spectroscopic data, including 1D and 2D NMR spectra. The relative and absolute configurations of 1-3 were determined using NOESY experiments and electronic circular dichroism analyses. Compounds 1, 4, 5, and 7 inhibited protein tyrosine phosphatase (PTP) 1B activity with IC50 values of 25, 11, 28, and 24 μM, respectively...

Diabetes is a chronic condition which is locally managed through the stem of Ficus foveolata . To find the exact chemical constituent responsible for this activity, a triterpene lactone (ficusonolide) isolated from F. foveolata was studied for antidiabetic potential through the in vitro antidiabetic paradigm employing L-6 cells and an in vivo antidiabetic assay against non-insulin-dependent rats. The results on glucose uptake in the L-6 cell line indicated that ficusonolide has enhanced the uptake of glucose by 53...

An extract from a PDB static culture of Malbranchea dendritica exhibited α-glucosidase and PTP-1B inhibitory activities. Fractionation of the active extract led to the isolation of gymnoascolide A ( 1 ), a γ-butenolide, and xanthones sydowinin A ( 2 ), sydowinin B ( 3 ), and AGI-B4 ( 4 ), as well as orcinol ( 5 ). Compound 1 exhibited important inhibitory activity against yeast α-glucosidase (IC50 = 0.556 ± 0.009 mM) in comparison to acarbose (IC50 = 0.403 ± 0.010 mM). Kinetic analysis revealed that 1 is a mixed-type inhibitor...

Diabetes, a glucose metabolic disorder, is considered one of the biggest challenges associated with a complex complication of health crises in the modern lifestyle. Inhibition or reduction of the dipeptidyl peptidase IV (DPP-IV), alpha-glucosidase, and protein-tyrosine phosphatase 1B (PTP-1B) enzyme activities or expressions are notably considered as the promising therapeutic strategies for the management of type 2 diabetes (T2D). Various food protein-derived antidiabetic bioactive peptides have been isolated and verified...

Endoplasmic reticulum (ER) stress contributes to endothelial dysfunction, which is the initial step in atherogenesis. Blockade of protein tyrosine phosphatase (PTP)1B, a negative regulator of insulin receptors that is critically located on the surface of ER membrane, has been found to improve endothelial dysfunction. However, the role of ER stress and its related apoptotic sub‑pathways in PTP1B‑mediated endothelial dysfunction, particularly its angiogenic capacity, have not yet been fully elucidated. Thus, the present study aimed to investigate the impact of PTP1B suppression on ER stress‑mediated impaired angiogenesis and examined the contribution of apoptotic signals in this process...

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals...

Chemical modification of the thiol group on protein tyrosine phosphatase (PTP) 1B triggers an activation of epidermal growth factor receptor (EGFR) signaling that is mimicked by environmental electrophiles through S-modification of PTP1B. While activation of PTP1B/EGFR by a single exposure to an electrophile has been established, the effects of combined exposure to electrophiles are unknown. Here, we examined the activation of EGFR signaling by combined exposure to ambient electrophiles in human epithelial carcinoma A431 cells...

The present study aimed to investigate the effects of mungbean water extract (MWE) on insulin downstream signaling in insulin-resistant HepG2 cells. Whole seed mungbean was extracted using boiling water, mimicking a traditional cooking method. Vitexin and isovitexin were identified in MWE. The results showed that MWE inhibited protein tyrosine phosphatase (PTP)-1B (IC50 = 10 μg/mL), a negative regulator of insulin signaling. MWE enhanced cellular glucose uptake and altered expression of genes involved in glucose metabolism, including forkhead box O1 (FOXO1), phosphoenolpyruvate carboxykinase (PEPCK), and glycogen synthase kinase (GSK)-3β in the insulin-resistant HepG2 cells...

Rohitukine (RH) was extracted from the stem bark of Dysoxylum binectariferum Hook. It was derivatized to different arylsulphanmides by treating with the corresponding aryl sulphonyl chlorides. These derivatives were tested in-vitro on protein tyrosine phosphatase 1B (PTP1B) inhibition. Among these the active compounds K2, K3, K5, and K8 significantly inhibited the PTP1B by 51.3%, 65.6%, 71.9%, and 55.9% respectively at 10 µg/ml, the results were also supported by in-silico docking experiments. The most potent compound K5 was analyzed for antidiabetic and antidyslipidemic activity in vivo...

Substituted phenylacetic ( 1-3 ), phenylpropanoic ( 4-6 ), and benzylidenethiazolidine-2,4-dione ( 7-9 ) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements...

Protein phosphorylation is an integral component of signal transduction pathways within eukaryotic cells, and it is regulated by coordinated interactions between protein kinases and protein phosphatases. Our previous study demonstrated differential expressions of serine/threonine protein phosphatases (PP2A and calcineurin) between diapause and developing eggs in Bombyx mori. In the present study, we further investigated expression of protein tyrosine phosphatases (PTPs) in relation to the Bombyx embryonic development...

Guavanoic acid functionalized gold nanoparticles exhibit anti-diabetic potential by improving insulin dependent glucose uptake in L6 rat skeletal muscle cells. The mode of action of the gold nanoparticles was established from the glucose uptake assay in the presence and absence of genistein and wortmannin. The anti-diabetic efficacy of guavanoic acid functionalized gold nanoparticles was put forth by in vitro assays like for PTP 1B, α-amylase and α-glucosidase enzyme activities. Studies on cytotoxicity revealed 50% inhibition of cells at 265 ± 0...

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder which is globally responsible for millions of fatalities per year. Management of T2DM typically involves orally administered anti-hyperglycaemic drugs in conjunction with dietary interventions. However, the current conventional therapy seems to be largely ineffective as patients continue to develop complications such as cardiovascular diseases, blindness and kidney failure. Existing alternative treatment entails the administration of organic therapeutic pharmaceuticals, but these drugs have various side effects such as nausea, headaches, weight gain, respiratory and liver damage...

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of chronic liver disease characterized by aberrant accumulation of triglycerides (TG) in hepatocytes without excessive alcohol consumption. Hepatic lipotoxicity derived from overaccumulation of free fatty acids is considered as one of the typical hallmarks of NAFLD. Insulin resistance (IR) and chronic inflammation are widely recognized as the key etiological factors associated with NAFLD. Dipeptidyl peptidase 4 inhibitor (DPP4i) is a novel pharmacological agent extensively applied in the treatment of Type 2 Diabetes Mellitus (T2DM) for decades which also have a liver protective effect...

BACKGROUND: The use of herbal therapies for treatment and management of diabetes mellitus and complications associated with this chronic condition is increasing. Plants contain a bounty of phytochemicals that have been proven to be protective by reducing the risk of various ailments and diseases, including alkaloids. Moreover, alkaloids are known to be among the oldest natural products used by humans for highlighting drugs that play crucial roles as therapeutic agents. The reason for this expanding interest and uses of alkaloids as a part of plant natural compounds-based treatments is that a significant proportion of diabetic patients do not respond very well to conventional therapeutic medication...

Bioassay screening using Indonesian plants, such as traditional foods (vegetables, spices, and tea) and folk medicinal herbs, identified eight protein tyrosine phosphatase (PTP) 1B inhibitory and two antibacterial plants. The leaves of Syzygium polyanthum (Wight) Walp. were examined in more detail to define PTP1B inhibitory components, resulting in the isolation of a new active acylbenzene (1) along with four related congeners of 1 (2-5) and four oleanane triterpenes (6-9). The structure of 1 was elucidated as 12-oxo-12-(2,3,5-trihydroxy-4-methylphenyl)dodecanoic acid based on its spectroscopic data...

An infusion prepared from the aerial parts of Salvia amarissima Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC50 ~88 and 33 μg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide ( 1 ), 5,6,4'-trihydroxy-7,3'-dimethoxyflavone ( 2 ), 6-hydroxyluteolin ( 3 ), rutin ( 4 ), rosmarinic acid ( 5 ), isoquercitrin ( 6 ), pedalitin ( 7 ) and a new neo -clerodane type diterpenoid glucoside, named amarisolide G ( 8a , b ). Compound 8a , b is a new natural product, and 2 - 6 are reported for the first time for the species...

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase (PTP) 1B (PTP1B) plays a critical role in the regulation of obesity, type 2 diabetes mellitus (T2DM), and other metabolic diseases. However, drug candidates exhibiting PTP1B selectivity and oral bioavailability are currently lacking. Here, the enzyme inhibitory characteristics and pharmacological benefits of BDB were investigated in vitro and in vivo. EXPERIMENTAL APPROACH: Surface plasmon resonance (SPR) assay was performed to validate the direct binding of BDB to PTP1B, and Lineweaver-Burk plotting of the enzymatic reaction was used to identify the inhibition type of BDB...

9,10-Phenanthrenequinone (9,10-PQ) is a polycyclic aromatic hydrocarbon quinone contaminated in diesel exhaust particles and particulate matter 2.5. It is an efficient electron acceptor that induces redox cycling with electron donors, resulting in excessive reactive oxygen species and oxidized protein production in cells. The current study examined whether 9,10-PQ could activate epidermal growth factor receptor (EGFR) signaling in A431 cells through S-oxidation of its negative regulators such as protein tyrosine phosphatase (PTP) 1B...

Diabetes and obesity have increased dramatically in recent decades worldwide. Diabetes mainly emerged as a major health care burden disease in both the US and other industrialized countries, among which type II diabetes is the most common. Discovering new and effective treatments for diabetes is currently a high international health priority. In the present study a computational technique was used to model 97 compounds with PTP-1B inhibitory activity, in order to demonstrate the Quantitative structure-activity relationship (QSAR) of these compounds a genetic function approximation (GFA) algorithm was applied to pick the best descriptors and multiple linear regression (MLR) was used to establish a relationship between the PTP-1B inhibitory activity of these compounds and the best molecular descriptors...