• Bulletin of the Korean Chemical Society
• /
• v.33 no.1
• /
• pp.275-277
• /
• 2012

• Bulletin of the Korean Chemical Society
• /
• v.34 no.8
• /
• pp.2487-2490
• /
• 2013

SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of $I{\kappa}B{\alpha}$ in macrophages. The effects of SA51 in mice were compared with those of structurally related compounds, SA18 and SA32, which were previously reported as inhibitors of both enzymes - less potent against $IKK{\beta}$ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for $IKK{\beta}^{+/-}$ mice. In contrast, SA18 and SA32 showed anti-obesity effects without anti-diabetic effects. Collectively, the effects of SA51 could be due largely to the inhibition of $IKK{\beta}$, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.

• Applied Biological Chemistry
• /
• v.51 no.3
• /
• pp.171-176
• /
• 2008

The comparative molecular similarity indices analysis (CoMSIA) models between 3${\beta}$-Hydroxy-12-oleanen-28-oic acid (1-30) analogues as substrate molecule and their inhibitory activities ($pI_{50}$) against protein tyrosine phosphatase (PTP)-1B were derived and discussed quantitatively. Listing in order, the CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR model, these QSAR models had the better statistical values. The optimized CoMSIA F1 model at grid 3.0${\AA}$ had the best predictability and fitness ($q^2$=0.754 and $r^2$=0.976) by field fit alignment. The order of contribution ratio (%) of CoMSIA fields concerning the inhibitory activities was a H-bond acceptor (48.9%), steric field (25.8%) and hydrophobic field (25.4%), respectively. Therefore, the inhibitory activities of substrate molecules against PTP-1B were dependent upon H-bond acceptor field (A) of $R_4$-group. From the analytical results of CoMSIA contour maps, oleanolic acid derivatives will have better inhibition activities if $R_1$ group has H-bond acceptor disfavor, $R_3$group has steric disfavor and $R_4$ group has steric, hydrophobic, H-bond favor.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.4
• /
• pp.1275-1277
• /
• 2013

• Food Science and Preservation
• /
• v.24 no.7
• /
• pp.1007-1016
• /
• 2017

Melania snail (Semisulcospira libertina) was traditionally used as the healthy food in Korea. It was generally known to improve liver function and heal a diabetes. The aim of this study was to elucidate the anti-diabetic mechanism of melanian snail hydrolysates treated with protamex (MPH) by investigating the inhibitory action on protein tyrosine phosphatase 1B (PTP1B), the improving effect on the insulin resistance in C2C12 myoblast and the protective effect for pancreatic beta-cell (INS-1) under the glucose toxicity. The melania snail hydrolysates treated with protamex (MPH), which showed the highest degree of hydrolysis (43%), and inhibited effectively PTP1B activity ($IC_{50}=15.42{\pm}1.1{\mu}g/mL$), of which inhibitory effect was higher than usolic acid, positive control ($IC_{50}=16.65{\mu}g/mL$). MPH increased the glucose uptake in C2C12 myoblast treated with palmitic acid. In addition, MPH increased insulin mRNA expression level by over 160% with enhanced cell viability in INS-1 cell under the high glucose concentration (30 mM). These results suggest that MHP may improve the diabetic symptom by the inhibiting the PTP1B activity, increasing the glucose uptake in muscle cell and protecting the pancreatic beta-cell from glucose toxicity.

• Journal of Life Science
• /
• v.33 no.10
• /
• pp.783-790
• /
• 2023

Modern people have an increased incidence of metabolic diseases due to changed eating habits, and diabetes is considered the most significant metabolic disease. Given that existing diabetes treatments are accompanied by side effects, the aim of this study was to identify traditional natural products that have anti-diabetic activity. The potential anti-diabetic and antioxidant activities of natural products were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, α-glucosidase assay, and protein tyrosine phosphatase 1B (PTP1B) inhibition assay. Methanol extracts of Ulmus davidiana var. japonica, Acer tegmentosum branches, Nelumbo nucifera seeds, and Carthamus tinctorius seeds were found to have high anti-diabetic activity and further fractionated with solvents using ethyl acetate and butanol. Consequently, the ethyl acetate fraction of C. tinctorius seeds (MG-11-E) with high α-glucosidase and PTP1B inhibitory activity was selected. MG-11-E was subjected to preparative thin layer chromatography, and fraction #6 showed high α-glucosidase and PTP1B inhibitory activity. Fraction #6 was analyzed and fractionated via high performance liquid chromatography with 50% methanol as the mobile phase, and anti-diabetic activity was observed in the sample that eluted after 4 min as a single peak. The α-glucosidase inhibitory activity exhibited by this sample seemed to be greater than the PTP1B inhibitory activity; thus, it was concluded that a greater anti-diabetic therapeutic effect may be achieved by combining this agent with natural products that inhibit PTP1B activity.

• Natural Product Sciences
• /
• v.27 no.2
• /
• pp.99-114
• /
• 2021

Type 2 diabetes mellitus (T2DM) and its complications are important noncommunicable diseases with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase inhibitors are recently approached and advanced for T2DM and its complications therapy. Matricaria chamomilla L. is acknowledged as a worldwide medicinal herb that has many beneficial health effects as well as antidiabetic effects. Our research was designed to determine the most potential antidiabetic phytochemicals from M. chamomilla employing in silico study. 142 phytochemicals were obtained from the databases. The first screening employed iGEMdock and Swiss ADME, involving 93 phytochemicals. Finally, 30 best phytochemicals were docked. Molecular docking and visualization analysis were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. Molecular docking results demonstrate that ligand-protein interaction's binding affinities were -5.16 to -7.54 kcal/mol and -5.30 to -12.10 kcal/mol for PTP1B and aldose reductase protein targets respectively. In silico results demonstrate that M. chamomilla has potential antidiabetic phytochemical compounds for T2DM and its complications. We recommended anthecotulide, quercetin, chlorogenic acid, luteolin, and catechin as antidiabetic agents due to their binding affinities against both PTP1B and aldose reductase protein. Those phytochemicals' significant efficacy and potential as antidiabetic must be investigated in further advanced research.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.34 no.2
• /
• pp.109-115
• /
• 2008

The comparative molecular field analyses(CoMFA) models between the substituents with changing groups($R_1{\sim}R_4$) of $3{\beta}$-hydroxy-12-oleanen-28-oic acid derivatives as substrate molecule and their inhibitory activities($pI_{50}$) against protein tyrosine phosphatase(PTP)-1B were derived and discussed quantitatively. The optimized CoMFA F1 model have best predictability and fitness($r^2_{cv.}=0.654$ and $r^2_{ncv.}=0.995$). The order of contribution ratio (%) with CoMFA fields on the inhibitory activities was a steric field(53.0%), electrostatic field(36.2%) and hydrophobic field(10.8%). From the analytical results of CoMFA contour maps, the inhibitory activities were dependent on the R4 group in substrate molecules. Particularly, the new active compounds(P1 & P2) with the inhibitory activity against melanin synthesis were expected.

• Journal of Microbiology and Biotechnology
• /
• v.22 no.7
• /
• pp.1029-1033
• /
• 2012

A number of evidence have been accumulated that the regulation of reversible tyrosine phosphorylation, which can be regulated by the combinatorial activity of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), plays crucial roles in various biological processes including differentiation. There are a total of 107 PTP genes in the human genome, collectively referred to as the "PTPome." In this study, we performed PTP profiling analysis of the HIB-1B cell line, a brown preadipocyte cell line, during brown adipogenesis. Through RT-PCR and real-time PCR, several PTPs showing differential expression pattern during brown adipogenesis were identified. In the case of PTP-RE, it was shown to decrease significantly until 4 days after brown adipogenic differentiation, followed by a dramatic increase at 6 days. The overexpression of PTP-RE led to decreased brown adipogenic differentiation via reducing the tyrosine phosphorylation of the insulin receptor, indicating that PTP-RE functions as a negative regulator at the early stage of brown adipogenesis.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.5
• /
• pp.1505-1508
• /
• 2012

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound ($\mathbf{4}$) was first observed to have moderate inhibitory activity against PTP1B with an $IC_{50}$ value of $13.72{\pm}1.53{\mu}M$. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound ($\mathbf{4}$) as the lead compound. Compound $\mathbf{4l}$ ($IC_{50}=3.12{\pm}0.18{\mu}M$) was 4.4-fold more potent than the lead compound $\mathbf{4}$ ($IC_{50}=13.72{\pm}1.53{\mu}M$), and more potent than the positive control, ursolic acid ($IC_{50}=3.40{\pm}0.21{\mu}M$). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.