• Journal of Marine Bioscience and Biotechnology
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• v.2 no.4
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• pp.230-233
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• 2007

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. As part of our searching for PTP1B inhibitors from natural products, the extracts of marine microorganisms were screened for the inhibitory effects on the activity of protein tyrosine phosphatase 1B (PTP1B). Among the tested 304 extracts, 29 extracts exhibited inhibition rate ranging 40.1 - 83.6 % against PTP1B at the concentration level of $30{\mu}g/mL$.

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

• Journal of Ginseng Research
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• v.38 no.1
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• pp.28-33
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• 2014

Background: Panax notoginseng has been used as a general tonic agent to invigorate human body for millennia in China and continued to be used until present. Methods: Some chromatographic methods were performed to isolate pure triterpenoids, and their structures were determined by nuclear magnetic resonance (NMR) experiments. Anti-diabetes activities of isolated compounds were evaluated through their inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) enzyme. Results and Conclusion: Three new dammarane-type triterpenoids, notoginsenoside-LX (1), notoginsenoside-LY (2), and notoginsenoside-FZ (3) together with eighteen known compounds were isolated from the Panax notoginseng leaves. The structure-activity relationship of the compounds with dammaranetype triterpenoids and their PTP1B inhibitory activity were also reported. Results showed that compounds 2, 15, 20, and 21 can significantly inhibit the enzyme activity of PTP1B in a dose-dependent manner, with inhibitory concentration 50 ($IC_{50}$) values of $29.08{\mu}M$, $21.27{\mu}M$, $28.12{\mu}M$, and $26.59{\mu}M$, respectively. The results suggested that Panax notoginseng leaves might have potential as a new therapeutic agent for the treatment of diabetes.

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

• Natural Product Sciences
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• v.13 no.4
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• pp.311-316
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• 2007

In this study, the twenty-four ethyl acetate extracts of twenty-two medicinal plants, traditionally used in Vietnam as anti-diabetes agents, were investigated for ${\alpha}$-amylase and protein tyrosine phosphatase 1B (PTP1B) enzymes inhibitory activity in vitro. The results indicated that, twelve materials (50.0%) showed moderate to strong inhibitory activity in ${\alpha}$-amylase inhibitory activity with $IC_{50}$ values ranging from 2.5 to $48.8{\mu}g/mL$; meanwhile, ten extracts (41.6%) could demonstrate PTP1B activity with $IC_{50}$ values less than $30.5{\mu}g/mL$. Some plants presented interesting activities against both of ${\alpha}$-amylase and PTP1B enzymes such as Catharanthus roseus, Carthamus tinctorius, Momordica charantia, Gynostemma pentaphyllum, Glycyrrhiza glabra, Smilax glabra, Psidium guajava (leave), and Rehmannia glutinosa. The study may provide a proof, at least in a part, for the ethno-medical use in diabetes disease of these plants.

• BMB Reports
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• v.45 no.3
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• pp.141-146
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• 2012

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPAR${\alpha}$ and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.319-326
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• 2023

Objectives: The study's goal was to find out whether Chrysanthemum rubellum extract has anti-diabetic properties by concentrating on α-glucosidase and the PTP-1B signaling pathway. C. rubellum flowers were used for extraction using Methanol/water (80/20) as solvent. Methods: LC-MS techniques was used to check the presence of phytoconstituents present in C. rubellum extract. In vitro antidiabetic activity was evaluated using α-glucosidase inhibitory activity and PTP-1B signaling pathway. On Streptozotocin (STZ)-induced rats with diabetes, the in vivo antidiabetic efficacy was assessed using a test for oral glucose tolerance. Results: The phytoconstituents identified in the extract of C. rubellum were apigenin, diosmin, myricetin, luteolin, luteolin-7-glucoside, and Quercitrin as compound 1-6, respectively. Results showed that diosmin exhibited highest α-glucosidase inhibitory activity i.e. 90.39%. The protein level of PTP-1B was lowered and the insulin signalling activity was directly increased by compounds 1-6. The maximum blood glucose levels were seen in all groups' OGTT findings at 30 minutes following glucose delivery, followed by gradual drops. In comparison to the control group, the extract's glucose levels were 141 mg/dL at 30 minutes before falling to 104 mg/dL after 120 minutes. The current study has demonstrated, in summary, that extract with phytoconstituents reduce blood sugar levels in rats. Conclusion: This finding suggests that extract may reduce the chance of insulin resistance and shield against disorders like hyperglycemia.

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

• Bulletin of the Korean Chemical Society
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• v.24 no.10
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• pp.1455-1464
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• 2003

Several series of compounds (benzoic acids, pyrazolecarboxylic acids, phenoxyacetic acids, and quinolinoxyacetic acids) were prepared and evaluated for their inhibitory activity against PTP-1B. Several compounds showed submicromolar inhibitory activity.

• Journal of Applied Biological Chemistry
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• v.50 no.2
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• pp.74-77
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• 2007

Crude extracts of 69 marine organisms (27 salt marsh plants and 42 seaweeds) were screened for the inhibitory activity against the protein tyrosine phosphatase 1B (PTP1) in vitro. The most active extracts were methanol extracts from Derbesia marina (80.6% in inhibitory activity) and Symphycladia latiscula (85.6%) at the concentration of $15{\mu}g/mL$. Methanol extracts of Codium adhaerens and Hisikia fuziformis were moderately inhibitory with 71.2 and 69.1% inhibition, respectively. It was peculiar that only the extracts from seaweeds show inhibitory activity where those from salt marsh plants do not show any significant effect.