PTP1B Enzyme Research Articles

Activation and friction in enzymatic loop opening and closing dynamics

Protein loop dynamics have recently been recognized as central to enzymatic activity, specificity and stability. However, the factors controlling loop opening and closing kinetics have remained elusive. Here, we combine molecular dynamics simulations with string-method determination of complex reaction coordinates to elucidate the molecular mechanism and rate-limiting step for WPD-loop dynamics in the PTP1B enzyme. While protein conformational dynamics is often represented as diffusive motion hindered by solvent viscosity and internal friction, we demonstrate that loop opening and closing is activated. It is governed by torsional rearrangement around a single loop peptide group and by significant friction caused by backbone adjustments, which can dynamically trap the loop. Considering both torsional barrier and time-dependent friction, our calculated rate constants exhibit very good agreement with experimental measurements, reproducing the change in loop opening kinetics between proteins. Furthermore, we demonstrate the applicability of our results to other enzymatic loops, including the M20 DHFR loop, thereby offering prospects for loop engineering potentially leading to enhanced designs.

α-Glucosidase Inhibitors Based on Oleanolic Acid for the Treatment of Immunometabolic Disorders

Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes.

1,5-Anhydro-d-glucitol derivative and galloylated flavonoids isolated from the leaves of Acer ginnala Maxim. as dual inhibitors of PTP1B and α-glucosidase enzymes: In vitro and in silico studies

Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46–12.65 μM) and α-glucosidase (IC50 values ranging of 0.88–6.06 μM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 μM) or α-glucosidase (acarbose, IC50 = 141.62 μM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.

Diarylheptanoids with hypoglycemic potency from the rhizomes of Kaempferia galanga

Five new diarylheptanoids, kaemgalangins A–E (1–5), and seven known ones were isolated from the rhizomes of Kaempferia galanga. The structures of new compounds were identified by spectroscopic analyses involving 1D and 2D NMR, HRESIMS, IR, UV, [α]D, ECD calculations, and chemical methods. All compounds were tested for their hypoglycemic effects against α-glucosidase, Gpa and PTP1B enzymes, and stimulative effects on GLP-1 secretion. Kaemgalangins A (1) and E (5) showed significant inhibition on α-glucosidase with IC50 values of 45.3 and 116.0 μM; renealtin B (8) showed inhibition on GPa with an IC50 value of 68.1 μM; whereas all compounds were inactive to PTP1B. Docking study manifested that 1 well located in the catalytic pocket of α-glucosidase and OH-4″ played important roles in maintaining activity. Moreover, all compounds showed obviously stimulative effects on GLP-1 with promoting rates of 826.9%–1738.3% in NCI-H716 cells. This study suggests that the diarylheptanoids in K. galanga have antidiabetic potency by inhibiting α-glucosidase and Gpa enzymes, and promoting GLP-1 secretion.

Oral sub-chronic treatment with Terminalia phaeocarpa Eichler (Combretaceae) reduces liver PTP1B activity in a murine model of diabetes.

The endemic Brazilian medicinal plants of the genus Terminalia (Combretaceae), popularly known as capitão, comprising the similar species Terminalia phaeocarpa Eichler and Terminalia argentea, are traditionally and indistinguishably used in the country to treat diabetes. The present work investigated the effect of 28 days of treatment with the crude ethanolic extract (CEE) and its derived ethyl acetate fraction (EAF) from T. phaeocarpa leaves in a mice model of diabetes. Streptozotocin-nicotinamide-fructose diabetic model was used to evaluate the antidiabetic activity of 28 days of treatment with the CEE and EAF from the leaves T. phaeocarpa and metformin as a positive control. Serum levels of total cholesterol, triglycerides, uric acid, ALP, AST, and ALT were measured with specific commercial kits and glucose with a strip glucometer. The thiobarbituric acid method measured the liver MDA level, while a colorimetric assay measured the GSH level and PTP1B activity. A UPLC-DAD profile was obtained to identify the main polyphenolic compound in the EAF. Treatment with CEE and EAF reduced plasma glucose in diabetic mice. At the end of the treatment, the plasma glucose level was significantly lower in EAF-treated (100 mg/kg) diabetic mice (106.1 ± 13.7 mg/dL) than those treated with 100 mg/kg CEE (175.2 ± 20.9 mg/dL), both significantly lower than untreated diabetic mice (350.4 ± 28.1 mg/dL). The serum levels of total cholesterol, triglycerides, uric acid, ALP, AST, and ALT were significantly reduced in diabetic mice treated with CEE and EAF. In the livers of diabetic mice, the treatment with CEE and EAF reduced MDA levels and the activity of the enzyme PTP1B (96.91 ± 3.7%, 113.8 ± 2.8%, and 134.8 ± 4.6% for CEE-, EAF-treated, and untreated diabetic mice, respectively). Galloylpunicalagin was the main polyphenol observed in the EAF of T. phaeocarpa. The present results demonstrate the significant antidiabetic effect of CEE and EAF of T. phaeocarpa and their reduction on the markers of liver dysfunction in diabetic mice. Moreover, the antidiabetic activity of T. phaeocarpa might be associated with lowering the augmented activity of the PTP1B enzyme in the liver of diabetic mice.

Integrated use of ligand and structure-based virtual screening, molecular dynamics, free energy calculation and ADME prediction for the identification of potential PTP1B inhibitors.

Protein tyrosine phosphatases (PTPs) are the group of enzymes that control both cellular activity and the dephosphorylation of tyrosine (Tyr)-phosphorylated proteins. Dysregulation of PTP1B has contributed to numerous diseases including Diabetes Mellitus, Alzheimer's disease, and obesity rendering PTP1B as a legitimate target for therapeutic applications. It is highly challenging to target this enzyme because of its highly conserved and positively charged active-site pocket motivating researchers to find novel lead compounds against it. The present work makes use of an integrated approach combining ligand-based and structure-based virtual screening to find hit compounds targeting PTP1B. Initially, pharmacophore modeling was performed to find common features like two hydrogen bond acceptors, an aromatic ring and one hydrogen bond donor from the potent PTP1B inhibitors. The dataset of compounds matching with the common pharmacophoric features was filtered to remove Pan-Assay Interference substructure and to match the Lipinski criteria. Then, compounds were further prioritized using molecular docking and top fifty compounds with good binding affinity were selected for absorption, distribution, metabolism, and excretion (ADME) predictions. The top five compounds with high solubility, absorption and permeability holding score of - 10 to - 9.3kcal/mol along with Ertiprotafib were submitted to all-atom molecular dynamic (MD) studies. The MD studies and binding free energy calculations showed that compound M4, M5 and M8 were having better binding affinity for PTP1B enzyme with ∆Gtotal score of - 24.25, - 31.47 and - 33.81kcal/mol respectively than other compounds indicating that compound M8 could be a suitable lead compound as PTP1B inhibitor.

Enzyme PTP-1B Inhibition Studies by Vanadium Metal Complexes: a Kinetic Approach.

The medical field now needs more novel drugs to treat obesity and type-2 diabetes mellitus (T2D) than ever before. Obesity and T2D are both characterized by resistance to the hormones leptin and insulin. PTP-1B is a promising target for drug growth, as strong genetic, pharmacological, and biochemical evidence points to the possibility of treating diabetes and obesity by blocking the PTP-1B enzyme. Studies have also found that PTP-1B is overexpressed in patients with diabetes and obesity, suggesting that inhibiting PTP-1B may be a useful technique in their care. There are no clinically used PTP-1B inhibitors, despite the fact that numerous naturally occurring PTP-1B inhibitors have demonstrated great therapeutic promise. This is most likely due to their low activity or lack of selectivity. It is still important to look for more effective and focused PTP-1B inhibitors. A few organovanadium metal complexes were synthesized and characterized, and binding studies on vanadium complexes with PTP-B were also performed using fluorescence emission spectroscopy. Additionally, we theoretically (molecular modeling) and experimentally (enzyme kinetics) examined the PTP-1B inhibitory effects of these vanadium metal complexes and found that they have excellent PTP-1B inhibitory properties.

Studies on the serum glucose reducing effect of vanadium metal complexes on Wistar rats

Few vanadium metal complexes of substituted acetyl acetones were synthesized, characterized and their anti-diabetic activities were evaluated. The purpose of this investigation is twofold. 1) To evaluate the inhibitory properties of these vanadium metal complexes on enzyme PTP-1B. 2) To know the ease with which these metal complexes are being transported by transporting proteins like BSA. To synchronize these results, experiments on induced diabetic Wistar Rats were conducted. Molecular modeling studies were also performed to support the in vitro results. Kinetic studies have shown that vanadium complexes are good inhibitors of PTP-1B enzyme. The order of glucose reducing properties of these metal complexes from different experiments is found to be the same. The vanadium ternary metal complex derived from 2,2,6,6-tetramethyl-3,5-heptanedione and imidazole as ligands has exhibited higher potency compared to methyl Imidazole and ethyl imidazole.

Investigation of Antidiabetic Effect of Pistacia atlantica Leaves by Activity-Guided Fractionation and Phytochemical Content Analysis by LC-QTOF-MS.

In this study, the antidiabetic, antiobesity, antioxidant, and antihyperlipidemic effects potential of Pistacia atlantica Desf. leaves were evaluated by in vitro methods. The effects of the leaves of the plant on pancreatic lipase, pancreatic cholesterol esterase, and PTP1B enzymes were investigated for the first time and it was observed that leaf methanol extract (IC50: 123.67 ± 0.40 μg/ml) and n-hexane sub-extract (IC50: 61.03 ± 0.11 μg/ml) had much stronger effects on pancreatic cholesterol esterase enzyme than simvastatin (IC50: 142.30 ± 5.67 μg/ml). The methanolic extract of P. atlantica leaves exerted strong inhibitory effect on the enzymes (α-amylase and α-glucosidase) effective on carbohydrate digestion. It was thought that the methanol extract could provide significant benefits against oxidative stress in diabetes mellitus since it showed antioxidant activities (DPPH radical scavenging activity and reducing power) as strong as reference compounds (ascorbic acid and quercetin). Qualitative and quantitative analyzes of rutin (0.328 ± 0.000 g/100 g dry extract), methyl gallate (5.245 ± 0.014 g/100 g dry extract), quercetin-3-O-glucoside (0.231 ± 0.000 g/100 g dry extract), and gallic acid (0.528 ± 0.127 g/100 g dry extract) in methanol extract were performed by RP-HPLC. The phytochemical content of the active sub-fraction obtained from the leaf methanol extract by activity-guided fractionation and column chromatography studies was characterized by LC-QTOF-MS. The presence of trigalloylglucose, digalloylglucose, and methyl gallate in the G6 coded sub-fraction obtained by chromatographic techniques from the ethyl acetate sub-extract, which has the highest inhibitory effect on α-amylase and α-glucosidase enzymes, was determined by LC-QTOF-MS. In addition to the G5 coded subfraction, a strong α-glucosidase enzyme inhibitory activity was also observed in the G6 coded sub-fraction, and methyl gallate, methyl digallate, 2″-O-galloyl-quercetin-3-O-hexoside, and myricetin-3-O-hexoside were identified in this sub-fraction. This study displayed that the methanol extract of P. atlantica leaves could be a potential source for bioactive compounds with antidiabetic effects by showing inhibitory effects on enzymes involved in carbohydrate digestion.

Multi-Mechanistic In Vitro Evaluation of Antihyperglycemic, Antioxidant and Antiglycation Activities of Three Phenolic-Rich Indian Red Rice Genotypes and In Silico Evaluation of Their Phenolic Metabolites.

The study evaluated the antidiabetic potential of three traditional Indian red rice genotypes/RR (Kattuyanam/KA, Chennangi/CH & Karungkuruvai/KU) using a combination of in vitro, metabolomics (Quadrupole-Time of Flight-Liquid chromatography-Mass spectrometry/Q-TOF-LC-MS/MS), and in silico techniques. In terms of antihyperglycemic potential, KA exhibited the highest inhibitory activity against α-amylase; CH against α-glucosidase; and KU against DPPIV and PTP1B enzymes. KA exhibited the highest antioxidant activity (DPPH, FRAP, and ABTS) and greater inhibition of protein glycation compared to other RR indicating its potential to mitigate diabetic complications. The metabolomic analysis confirmed the presence of 99 phenolics in the sample extracts (KU-71, KA-70, CH-68). Molecular docking studies revealed seven metabolites to be good inhibitors of the four target enzymes and activators of insulin receptor substrate/IRS. The antihyperglycemic and oxidation-glycation reduction composite index revealed KA to have the highest overall antidiabetic potential. Hence, the RR could be utilized in functional foods with a multi-barrelled strategy for diabetes prevention/management.

Isolation, Structural Characterization and Antidiabetic Activity of New Diketopiperazine Alkaloids from Mangrove Endophytic Fungus Aspergillus sp. 16-5c.

Six new DIKETOPIPERAZINE alkaloids aspergiamides A–F (1–6), together with ten known alkaloids (7–16), were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5c. The structures of the new compounds were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of aspergiamides A-F were established based on the experimental and calculated ECD data. All the compounds were evaluated for the antidiabetic activity against α-glucosidase and PTP1B enzyme. The bioassay results disclosed compounds 1 and 9 exhibited significant α-glucosidase inhibitory with IC50 values of 18.2 and 7.6 μM, respectively; compounds 3, 10, 11, and 15 exhibited moderate α-glucosidase inhibition with IC50 values ranging from 40.7 to 83.9 μM; while no compounds showed obvious PTP1B enzyme inhibition activity.

Unique Mechanisms in Treatment of Diabetes mellitus: A Herbal-Based Therapeutic Approach

Diabetes mellitus is a chronic metabolic disease that affects millions of people worldwide, described by hyperglycemia due to impaired insulin secretion, insulin action or both. As a consequence of the persistent hyperglycemia, several microvascular and macrovascular complications arise. In herbal treatments, there are quite a variety of mechanisms and pathways that could be targeted while considering the treatment of type II diabetes mellitus (T2DM); ranging from acting on pancreatic insulin, decreasing carbohydrates digestion, to inhibiting enzymes responsible for this disease like glucosidases, maltase fructose-1,6-bisphosphatase, G6Pase and PTP1B enzymes and increasing GLUT-2 and GLUT-4 translocation. There is a diverse amount of plants that have individual active constituents that are responsible for their anti-diabetic effect; such constituents belong to classes like flavonoids, phenolic compounds and alkaloids. In our review, we will report a large variety of plants and phytoconstituents that have anti-diabetic action and discuss their mechanism of action highlighting their uniqueness and thus, providing for novel targets for anti-diabetic molecules either solely or as adjunctive therapies. Ethnopharmacological studies could aid in the selection of medicinal plants to be employed in these preliminary studies. However, the exact bioactive metabolite, along with the definite mechanism of action, should be studied before experimental and clinical studies.

Effectiveness of cyclohexyl functionality in ugonins from Helminthostachys zeylanica to PTP1B and α-glucosidase inhibitions

Ugonins are unique flavonoids with cyclohexyl motif from Helminthostachys zeylanica. Ugonins (1–6) from the target plant displayed significant inhibitions against both PTP1B (IC50s = 0.6–7.3 μM) and α-glucosidase (IC50s = 3.9–32.9 μM), which are crucial enzymes associated with diabetes. A cyclohexyl motif was proved to be the key functionality for PTP1B and α-glucosidase. For example, 1 was 26-fold effective to PTP1B and 15-fold to α-glucosidase than its mother compound, luteolin. This tendency was well elucidated with distinctive differences of binding affinities (KSV) between ugonins and mother compounds to PTP1B enzyme. Inhibitory mechanisms to PTP1B and α-glucosidase were fully characterized to be competitive, non-competitive and mixed type I according to the position of cyclohexyl functionality. In particular, the ugonin J (1) has a cyclohexyl on the B ring was estimated as a reversible, competitive and a slow binding inhibitor with parameters: Kiapp = 0.1234 μM, k3 = 0.5713 μM−1 min−1, and k4 = 0.0705 min−1. In-depth molecular docking experiments disclosed the specific binding sites and residues of competitive inhibitor (1) and non-competitive inhibitor (4) to PTP1B enzymes. As well, all six ugonins (1–6) also inhibited α-glucosidase effectively, in which cyclohexyl motif was also the key functionality of inhibitions.

PTP1B INHIBITORS FROM ISODON TERNIFOLIUS COLLECTED IN VIETNAM

From the whole plant of Isodon ternifolius collected in Vietnam, four triterpens including ursaldehyde (1), ursolic acid (2), b-sitosterol (3) and b-sitosteryl ferulate (4) were purified. Their chemical structures were determined by interpretation of NMR and MS data and comparison with the literatures. Compounds 1-4 were evaluated for their inhibitory activity against PTP1B enzyme activity using in vitro assay. Compounds 1 and 2 displayed potential activities with IC50 values of 16.92 ± 0.12 and 3.42 ± 0.45 μM, respectively. This is the first time that compounds 1 and 4 have been isolated from the Isodon genus and I. ternifolius has been evaluated for the PTP1B inhibitory activity.

PTP1B and α-glucosidase inhibitors from Selaginella rolandi-principis and their glucose uptake stimulation.

As part of an ongoing search for new protein tyrosine phosphatase 1B inhibitors and glucose uptake stimulators from nature, a new coumarin, selaginolide A (1) and four known isoflavones (2‒5) were isolated from the ethanol extract of a Vietnamese medicinal plant Selaginella rolandi-principis. The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds 3‒5 have been identified from Selaginella genus for the first time. The antidiabetic properties of the isolates (1‒5) were investigated using in vitro assay on 2-NBDG uptake in 3T3-L1 adipocytes and against PTP1B and α-glucosidase enzyme activities as well. Compounds 1 exhibited the most potency with inhibitory IC50 values of 7.40 ± 0.28 and 7.52 ± 0.37µM against PTP1B and α-glucosidase, respectively. Compounds 3 and 5 possessed potential inhibitions on PTP1B enzyme with IC50 values of 23.02 ± 1.29 and 11.08 ± 0.92µM and moderate inhibitions on α-glucosidase with IC50 values of 36.47 ± 1.87 and 55.73 ± 2.58µM, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC50 > 30µM) but displayed remarkable α-glucosidase inhibition with IC50 values of 3.39 ± 0.87 and 9.72 ± 0.62µM, respectively. Furthermore, ursolic acid as a positive control (IC50 3.42 ± 0.26µM) and compounds 1 and 5 acted as mixed-competitive inhibitors against PTP1B enzyme with Ki values of 6.46, 10.28, and 15.01µM, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10µM. The obtained result might suggest the potential of new coumarin (1) as a new type of natural PTP1B and α-glucosidase inhibitor for further research and development of antidiabetic and obese agents.Graphic abstract.

Natural plant-derived polygalacturonic acid-oleanolic acid assemblies as oral-delivered nanomedicine for insulin resistance treatment

Exogenous insulin administration is still the most used treatment for diabetes (mainly used for type-1 diabetes in clinic), however type 2 diabetes (T2D) with the characteristics of insulin resistance accounts for the vast majority proportion (90–95%) of diabetic population, which makes insulin function failure. Currently, many efforts have been devoted to insulin delivery with nanomedicine means, whereas the treatment of insulin resistance in T2D using nanotechnology strategy is rarely reported. In this study, we transformed a plant-derived natural insulin sensitizer into biocompatible nano-transport system, where the natural insulin sensitizer oleanolic acid (OA) was conjugated onto natural polymer polygalacturonic acid (PGA) to form self-assembled micelles as oral administrated nanomedcine for insulin resistance treatment in T2D. In vitro and in vivo investigation demonstrated that OA loaded PGA-OA micelles possess stability to cross the gastrointestinal barriers and improve drug intestinal absorption, remarkably maintaining plasma drug concentration for a longer time. Therefore, this formulation manifested good reversal effect on insulin resistance in the T2D rat model, and thereby exhibited long-term outcomes in glucose level control even after drug withdrawal. Additionally, the molecular mechanism of OA loaded PGA-OA mediated insulin-resistant reversal was found that it was probable mediated by promoting IRS-1/PI3K/AKT signaling pathway and inhibiting the activity of PTP1B enzyme simultaneously. In this regard, such a facile, safe and potent nanomedicine strategy may be promising alternative for long-acting insulin-resistant treatment in T2D therapy.

Chemical constituents from the roots of Kadsura coccinea with their protein tyrosine phosphatase 1B and acetylcholinesterase inhibitory activities.

Kadsura coccinea (Lem.) A. C. Smith has been used as a tonic, decongestant, and digestive agent. The roots are also employed in traditional medicine to treat chronic enteritis, acute gastritis, duodenal ulcers, rheumatic pain in bone, and traumatic injuries. In the present study, we have described the biological evaluation of constituents from the roots of K. coccinea with PTP1B and AChE inhibitory activities for the first time in literature. A new compound (1), kadcoccilactone T, and 24 known ones (2‒25) were isolated and identified using spectroscopic methods. All the isolates were examined for PTP1B and AChE inhibitory activities. Compounds 4 and 8 expressed strong PTP1B inhibition with IC50 values of 1.57 ± 0.11 and 3.99 ± 1.08μM, respectively. Apparently, these compounds were further studied for PTP1B enzyme kinetic analysis. The result indicated that compounds 4 and 8 exhibited mixed-type inhibition with the Κi values of 4.97 and 3.26µM, respectively.

Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors

A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2-23.2 µg/mL) and PTP1B (IC50 = 2.9-21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

Chemical and Pharmacological Evaluation of Hulls of Prunus dulcis Nuts.

Researchers have shown that the almond hulls, normally wasted after utilization of nuts, contain a number of biologically active compounds based on which the present study has been carried out. Focus is placed on the mass spectrometric determination of the analytes along with the estimation of total polyphenolic and total flavonoid contents in the 70% ethanol extract. After partitioning the 70% ethanol extract in hexane, chloroform, ethyl acetate, n-butanol, and water, all the extracts were evaluated for their antioxidant, antidiabetic, and antimicrobial activities. The results delivered total polyphenolic compounds as gallic acid equivalents (1% w/w) of the dried extract and total flavonoid contents as quercetin equivalents (0.2% w/w) of the dried extract. Mass spectrometric analysis resulted in the identification of 15 compounds containing various derivatives of (epi)catechin, chlorogenic acid, kaempferol, isorhamnetin and their glycosides, ursolic acid, amygdalactone, and benzoic acid derivatives. Antioxidant activity experiments showed that highest activity was found in n-butanol extract among the studied samples with IC50 value as 76.04 μg/ml, while hexane and chloroform extracts were active against the PTP1B enzyme with IC50 values 9.66 μg/ml and 37.95 μg/ml, respectively. Hexane and chloroform fractions were active against Staphylococcus aureus with the zone of inhibition diameter 9 mm and 12 mm, respectively.

Protein tyrosine phosphatase 1B inhibitory activities of compounds isolated from Polygonum cuspidatum

AbstractIn the search for new natural PTP1B inhibitory compounds from medicinal plants, two 9,10‐anthraquinones were isolated and structurally identified as physcion (1) and emodin (2) from the alcoholic extract of the root of Polygonum cuspidatum. Chemical structures of these isolates were identified by interpretation of spectroscopic data (1H, 13C NMR and MS) as well as comparing with reported literatures. Compounds 1–2 possessed inhibitory activity on PTP1B enzyme with IC50 values of 26.1 ± 0.7 and 13.3 ± 0.4 μM, respectively. Ursolic acid was used as positive control showing an IC50 value of 3.5 ± 0.2 μM in this assay. This result reveals that these 9,10‐anthraquinones might be considered as new natural compounds for development of antidiabetic agents.