Publications by authors named "Hassan Rasouli"

18 Publications

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Antioxidant and glycohydrolase inhibitory behavior of curcumin-based compounds: Synthesis and evaluation of anti-diabetic properties in vitro.

Bioorg Chem 2021 May 11;110:104720. Epub 2021 Feb 11.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Naturally occurring anti-diabetic compound curcumin can prevent diabetes complications due to antioxidant and anti-inflammatory properties as well as the attenuation of postprandial hyperglycemia. In this line, we have synthesized thirteen curcumin based derivatives (L1-L13) by multi-component reaction, characterized by IR, HNMR, 13C NMR, MS, elemental analysis and evaluated for possible antioxidant properties and α-glucosidase (α-Glu) and α-amylase (α-Amy) inhibitory potential. The curcumin-based pyrano[2,3-d]pyrimidine derivatives could inhibit α-Glu and α-Amy enzyme activity which showed desirable antioxidant activity. Furthermore, among the series, L5, L12, L9, L10, L8 and L11 were identified as more potent inhibitors of α-Glu enzyme than curcumin and the compounds of L12, L4, L9, L5, L10, L8, L13, and L11 were the stronger inhibitors of the α-Amy enzyme in vitro. Besides, among them, L12 had the lowest IC for the inhibition of both enzymes. Since strong inhibitors for pancreatic α-Amy result in the progression of severe gastrointestinal side effects, the inhibitors that show the lower α-Amy/α-Glu inhibitory ratio have attracted much attention in medicinal chemistry. Besides, considering antioxidant characteristics of synthesized compounds, the L7 derivative with the highest antioxidant activity and the lowest "α-Amy/α-Glu inhibitory" ratio could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs.
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http://dx.doi.org/10.1016/j.bioorg.2021.104720DOI Listing
May 2021

Deciphering inhibitory activity of flavonoids against tau protein kinases: a coupled molecular docking and quantum chemical study.

J Biomol Struct Dyn 2020 Sep 8:1-14. Epub 2020 Sep 8.

Department of Chemistry, Federal University of Lavras, Lavras, Brazil.

Today, Alzheimer's disease (AD) is one of the most important neurodegenerative disorders that affected millions of people worldwide. Hundreds of academic investigations highlighted the potential roles of natural metabolites in the cornerstone of AD prevention. Nevertheless, alkaloids are only metabolites that successfully showed promising clinical therapeutic effects on the prevention of AD. In this regard, other plant metabolites such as flavonoids are also considered as promising substances in the improvement of AD complications. The lack of data on molecular mode of action of flavonoids inside brain tissues, and their potential to transport across the blood-brain barrier, a physical hindrance between bloodstream and brain tissues, limited the large-scale application of these compounds for AD therapy programs. Herein, a coupled docking and quantum study was applied to determine the binding mode of flavonoids and three protein kinases involved in the pathogenesis of AD. The results suggested that all docked metabolites showed considerable binding affinity to interact with target receptors, but some compounds possessed higher binding energy values. Because docking simulation cannot entirely reveal the potential roles of ligand substructures in the interaction with target residues, quantum chemical analyses (QCAs) were performed to cover this drawback. Accordingly, QCAs determined that distribution of molecular orbitals have a pivotal function in the determination of the type of reaction between ligands and receptors; therefore, using such quantum chemical descriptors may correct the results of virtual docking outcomes to highlight promising backbones for further developments.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1814868DOI Listing
September 2020

Curcumin-based antioxidant and glycohydrolase inhibitor compounds: Synthesis and in vitro appraisal of the dual activity against diabetes.

Med Chem 2020 May 5. Epub 2020 May 5.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah. Iran.

Background: Curcumin, as the substantial constituent of the turmeric plant (Curcuma longa), plays a significant role in the prevention of various diseases, including diabetes. It possesses ideal structure features as enzyme inhibitor, including a flexible backbone, hydrophobic nature, and several available hydrogen bond (H-bond) donors and acceptors.

Objective: The present study aimed at synthesizing several novel curcumin derivatives and further evaluation of these compounds for possible antioxidant and anti-diabetic properties along with inhibitory effect against two carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, as these enzymes are therapeutic targets for attenuation of postprandial hyperglycemia.

Methods: Therefore, curcumin-based pyrido[2,3-d]pyrimidine derivatives were synthesized and identified using an instrumental technique like NMR spectroscopy and then screened for antioxidant and enzyme inhibitory potential. Total antioxidant activity, reducing power assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH• ) radical scavenging activity were done to appraisal the antioxidant potential of these compounds in vitro.

Results: Compounds L6-L9 showed higher antioxidant activity while L4, L9, L12 and especially L8 exhibited the best selectivity index (lowest α-amylase/α-glucosidase inhibition ratio).

Conclusion: These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index but also to limit the activity of the major reactive oxygen species (ROS) producing pathways.
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http://dx.doi.org/10.2174/1573406416666200506083718DOI Listing
May 2020

Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives.

Pharmacol Res 2020 05 24;155:104723. Epub 2020 Feb 24.

University of Belgrade, Faculty of Agriculture, Department of Food Technology and Biochemistry, 11080 Belgrade, Serbia.

Diabetes mellitus (DM) is a chronic metabolic disease which causes millions of death all over the world each year, and its incidence is on increase. The most prevalent form, type 2 DM, is characterized by insulin resistance and β-cell dysfunction, whereas type 1 DM is due to insulin deficiency as a result of β-cell destruction. Various classes of synthetic drugs have been developed to regulate glucose homeostasis and combat the development of late-diabetic complications. However, several of these chemical agents are either sub-optimal in their effect and/or may have side effects. Biologically, alkaloids unveiled a wide range of therapeutic effects including anti-diabetic properties. The chemical backbones of these compounds have the potential to interact with a wide range of proteins involved in glucose homeostasis, and thus they have received increasing attention as reliable candidates for drug development. This review sets out to investigate the anti-diabetic potential of plant alkaloids (PAs), and therefore, scientific databases were comprehensively screened to highlight the biological activity of 78 PAs with a considerable anti-diabetic profile. There are not enough clinical data available for these phytochemicals to follow their fingerprint in human, but current studies generally recommending PAs as potent α-glucosidase inhibitors. Except for some classes of monoterpene alkaloids, other compounds showed similar features as well as the presently available anti-diabetic drugs such as amino sugars and other relevant drugs. Moreover, the evidence suggests that PAs have the potential to be used as alternative additives for the treatment of DM, however, further in vitro and in vivo studies are needed to validate these findings.
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http://dx.doi.org/10.1016/j.phrs.2020.104723DOI Listing
May 2020

Characterization of MgO nanocatalyst to produce biodiesel from goat fat using transesterification process.

3 Biotech 2019 Nov 30;9(11):429. Epub 2019 Oct 30.

Department of Chemical Engineering, Bushehr Branch, Islamic Azad University, Bushehr, Iran.

In this study, biodiesel was produced from goat fat in the presence of magnesium oxide (MgO) nano-catalyst using transesterification process. The characteristics of the catalyst were studied using field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET), energy dispersive X-ray/mapping (EDX/Map), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and dynamic light scattering (DLS). The result showed that the specific surface area and the average pore diameter of the nanocatalyst were 40.44 m/g and 36.7 nm, respectively, which showed that the catalyst is mesoporous. According to the results of the DLS analysis, the average particle size of the catalyst was determined to be 5.5 nm. Also, the maximum biodiesel yield of 93.12% was obtained at temperature of 70 °C, methanol/oil molar ratio of 12:1, the catalyst content of 1 wt.%, and reaction time of 3 h. In addition, biodiesel was mixed with diesel at different ratios (B25, B50, B75, and B100) to improve fuel properties of the produced biodiesel. The results indicated that the mixtures of B75 and B100 had better density, viscosity, and flash point in comparison to the other mixtures and their properties were within the range of international standards.
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http://dx.doi.org/10.1007/s13205-019-1963-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821907PMC
November 2019

Devil's hand conceals behind the obscure side of AgNPs: A letter to the editor.

Authors:
Hassan Rasouli

Int J Biol Macromol 2019 Mar 8;125:510-513. Epub 2018 Dec 8.

Medical Biology Research Center (MBRC), Kermanshah University of Medical Science, Kermanshah, Iran.. Electronic address:

From that time AgNPs become one of the most accessible and important antibacterial agents in our world, thousands of papers published regarding investigating all aspects of these materials. When the time elapsed and novel methods contrived to follow the fingerprint of AgNPs in the in vivo models, some critical concerns and arguments also appeared between researchers about the safety of these compounds for living cells and vital organs. The paper by Dehvari and Ghahaghaei published in Volume 108 International Journal of Biological Macromolecules, pages 1128-1139 (Dehvari and Ghahghaei, 2018) suffered some errors from safety concerns to obscurities in the results essentially needing the amendment to enhance its quality. Though the author(s) idea is commended enough, nevertheless, I could not find a profound trace with their results, and my concerns are discussed in detail as the following lines.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.12.076DOI Listing
March 2019

L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells.

Food Chem Toxicol 2019 Jan 10;123:399-411. Epub 2018 Nov 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Reducing the adverse effects of chemotherapy on normal cells such as endothelial cells is a determinant factor of treatment success especially in pregnant women. In this regard, modulatory effect of L-arginine on various cancers is still a controversial topic in cancer therapy. So, this study aimed to compare the effect of L-arginine treatment alone and in combination with 5-fluorouracil (5-FU) on the survival and angiogenesis of primary human umbilical vein endothelial cells (HUVECs) and the breast cancer cell line of MDA-MB-468. Combinations of L-arginine and 5-FU increased cell survival in HUVECs but induced cell death in MDA-MB-468 cells. Nitric oxide assay showed an increase of this molecule in both cell lines. Assessments of metabolic changes as well as molecular docking indicated a decrease in glycolytic activity of cancer cells but not normal cells. Angiogenesis induction in HUVECs was confirmed through VEGF and MMP-2,9 up-regulated gene expressions. However, a down-regulation of the above-mentioned genes expression was observed in MDA-MB-468. Furthermore, an in vivo increased angiogenesis and decreased embryo toxicity was observed in combination treatment. Altogether, these findings clearly suggest that L-arginine inhibits cell death induced by 5-FU in HUVECs through attenuating the adverse effects of 5-FU, while it does not do so in breast cancer cells.
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http://dx.doi.org/10.1016/j.fct.2018.11.018DOI Listing
January 2019

Comparative in vitro/theoretical studies on the anti-angiogenic activity of date pollen hydro-alcoholic extract: Highlighting the important roles of its hot polyphenols.

Bioimpacts 2018 14;8(4):281-294. Epub 2018 Jun 14.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Date palm pollen (DPP) is the male reproductive soft powder from date flowers widely used as the valuable dietary supplement to fortify the size of testis and ovarian to increase the power of sex. This part of date palm significantly exhibited anti-diabetic, anti-inflammation and protective effects against male and female infertility. Though the anticancer activity of date fruits was previously reported, the DPP anti-angiogenic effects were not reported, and as the first study, its inhibitory effects were examined in the current study. The DPP soft powder was collected to prepare its hydro-alcoholic extract to examine its anti-angiogenic activity in an model. At different concentrations, the cytotoxicity of the prepared extract was examined on human umbilical vein endothelial cells (HUVECs) using lactate dehydrogenase method. Cell proliferation was determined using the MTT assay and cytodex-3D model in collagen gel was used to assay its possible anti-angiogenic activity. The expression of VEGF, and genes was measured using real-time polymerase chain reaction (PCR). Finally, molecular docking simulation was used to highlight the possible role of DPP polyphenols to interact with the associated receptors. The prepared hydro-alcoholic extract exhibited significant anti-angiogenic activity in a dose-dependent manner and decreased the endothelial cell proliferation. The calculated IC value for the examined extract in angiogenesis model was 260 µg·mL, respectively. Also, the expression of VEGF, and genes were significantly decreased. Docking simulation results unveiled that the isolated DPP polyphenols have the affinity to interact with ctDNA, VEGF and its receptors. The DPP is the new source of non-toxic anti-cancer agents to use as a dietary supplement in the pre-treatment of cancer.
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http://dx.doi.org/10.15171/bi.2018.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209826PMC
June 2018

Correction to: Efficient Differentiation of Human Embryonic Stem Cells Toward Dopaminergic Neurons Using Recombinant LMX1A Factor.

Mol Biotechnol 2019 Jan;61(1):72

Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.

The original version of this article was published without article note. The article note is given below.
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http://dx.doi.org/10.1007/s12033-018-0131-2DOI Listing
January 2019

2-Methylpyridine-1-ium-1-sulfonate as an Inducer of Apoptosis and Cell Cycle Arrest: A comparative in vitro and Computational Study.

Nutr Cancer 2019 1;71(4):643-656. Epub 2018 Oct 1.

a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

"Let food be thy medicine and thy medicine be thy food" was expressed by Hippocrates and the health benefits of medicinal plants and natural products have been considered by humans since historic times. The current study aims to investigate the anti-cancer activity of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from bulbs of Allium hirtifolium. The MPS compound (in a dose-dependent manner) induced arrest the AGS cells in G1 and G2/M phases, and Caco-2 cells in G1 and S phases. These findings were associated with the down-regulation of cyclin D1, CDK4, and up-regulation of p21, p27 and p53. According to the morphological observations and DNA fragmentation assay, the MPS compound induced apoptosis in both cell lines, and also cause a significant increase in the expression of Bax/Bcl-2. In this context, our molecular docking results unveiled that the MPS compound has considerable affinity to interact with the minor groove of ctDNA and also with cell cycle kinases. To approve and find the accurate MPS mode of action against cancer cell lines (especially in gastrointestinal cancer) further studies is highly recommended.
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http://dx.doi.org/10.1080/01635581.2018.1506495DOI Listing
May 2020

Synthesis, characterization, anti-diabetic potential and DFT studies of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde oxime.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Dec 6;205:111-131. Epub 2018 Jul 6.

Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran.

A new compound named 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde oxime (7-Oxime) was synthesized and characterized by FT-IR, FT-Raman, H NMR and C NMR techniques. The conformer possibilities were studied to find the most stable conformer and its molecular geometry. Then, the dimer form of the most stable monomer was built and optimized. Density functional theory (DFT) B3LYP method with 6-311++G(d,p) basis set was applied to analyze the molecular electrostatic potential (MEP), HOMO and LUMO orbitals, the vibrational wavenumbers, the infrared intensities, the Raman scattering activities and several thermodynamic properties (at different temperatures). The stability of the molecule derived from hyperconjugative interactions and charge delocalization has been analyzed by using natural bond orbital (NBO) analysis. In order to find the possible inhibitory activity of 7-Oxime, an accurate molecular blind docking simulation was performed. The results indicated that the mentioned compound has a good binding affinity to interact with the active sites of human α-glucosidase and α-amylase. For the first time, our computational finding suggests that this compound has a potential to be used as a supplementary agent in the pre-management of diabetes mellitus.
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http://dx.doi.org/10.1016/j.saa.2018.07.009DOI Listing
December 2018

Comparative antibacterial effects of cellulose nanofiber, chitosan nanofiber, chitosan/cellulose combination and chitosan alone against bacterial contamination of Iranian banknotes.

Int J Biol Macromol 2018 Oct 30;118(Pt A):1045-1054. Epub 2018 Jun 30.

Medical Biology Research Center (MBRC), Kermanshah University of Medical Science, Kermanshah, Iran. Electronic address:

The aims of the current study were to evaluate the antibacterial effects of cellulose nanofiber (CNF), chitosan nanofiber (ChNF), CNF/ChNF combination and chitosan alone (Ch) against the isolated bacterial contaminations from the surface of Iranian banknotes using biochemical, disc diffusion and molecular analyses. The results unveiled that the CNF did not show the significant antibacterial effect against isolated bacterial strains, whereas the combination of CNF/ChNF (at concentration 100 μg/disc 1:1) exhibited the synergistic effects against Stenotrophomonas maltophilia. Also, ChNF (100 μg/disc) and Ch (100 and 200 μg/disc) displayed dose-dependent antibacterial effects against the sensitive bacteria including Bacillus subtilis, Bacillus pumilus, Micrococcus sp. Kosakonia cowanii, Brevibacterium frigoritolerans, Escherichia coli standard ATCC 25922, Staphylococcus aureus standard ATCC 25923. On the other hand, chitosan displayed the highest inhibitory effects against Gram-positive bacteria. Our results showed that the coating of banknotes with these compounds is a novel strategy to reduce the bacterial contaminations and increase the durability (or quality) of banknotes, without being toxic to the surrounding environment.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.06.160DOI Listing
October 2018

Comparative experimental/theoretical studies on the EGFR dimerization under the effect of EGF/EGF analogues binding: Highlighting the importance of EGF/EGFR interactions at site III interface.

Int J Biol Macromol 2018 Aug 14;115:401-417. Epub 2018 Apr 14.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Epidermal growth factor receptors (EGFRs) and their cytoplasmic tyrosine kinases play significant roles in cell proliferation and signaling. All the members of the EGFR/ErbB family are primary goals for cancer therapy, particularly for tumors of breast, cervix, ovaries, kidney, esophagus, prostate and non-small-cell lung carcinoma and head and neck tumors. However, the therapeutic ability of accessible anti-ErbB agents is limited. Therefore, recognizing EGF analogues or small organic molecules with high affinity for the extracellular domain of the EGFR is a critical target on cancer research. An effective EGF analogue should have a comparable binding affinity for EGFR in order to create an effective ligand competitive inhibition against circulating wild EGF while fails to transduce appropriate downstream signaling into the cancer cell. In our earlier study we have developed a mutant form of human EGF (mEGF, lacking the four critical amino acid residues; Gln, Tyr, Arg and Asp at the C-terminal of the protein) and its binding properties and mitogenic activity were assessed. The mEGF showed high affinity for EGFR binding domains but caused poor EGFR dimerization and phosphorylation and especially, mEGF induced EGFR internalization. However, underlying mechanism of action of EGF analogues is still unclear and thus considered to be worthwhile for further study. With regard to different effects of the EGF analogue on EGFR activating process, computational analysis of wild EGF/EGFR and mEGF/EGFR complexes (along with EGFt/EGFR complex) were done. Results of the protein dissection identified several interactions within "ligand/EGFR" that are common among EGF and EGFt/mEGF. These results disclose that while several interactions are conserved within EGF/EGFR interfaces, EGF/EGFR interactions on site III interface controls the affinity, EGFR dimerization and subsequent downstream signaling through a heterogeneous set of non-covalent interactions. These findings not only represent the EGFR dynamics complexity but also smooth the path for structure-based design of therapeutics targeting C-terminal region of EGF (and the related domain within the receptor) or EGFR-based imaging probes.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.04.066DOI Listing
August 2018

2-Methylpyridine-1-ium-1-sulfonate from Allium hirtifolium: An anti-angiogenic compound which inhibits growth of MCF-7 and MDA-MB-231 cells through cell cycle arrest and apoptosis induction.

Biomed Pharmacother 2017 Sep 16;93:117-129. Epub 2017 Jun 16.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Natural products have well been recognized as sources of drugs in cancer treatment. Some medicinal plants contain the constituents with potent anti-angiogenic and anti-cancer effects, which have offered great hopes of being used as drugs for treating various cancers. The present study aims at identifying the anti-angiogenic effects of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from the ethyl acetate extract (EA) of Persian shallot (Allium hirtifolium). In a concentration-dependent manner, the MPS was able to inhibit endothelial cell migration and angiogenesis in both in vivo and in vitro assays, and also significantly suppressed proliferation of MCF-7 and MDA-MB-231 human breast cancer cell lines. Additionally, treatment with MPS showed a significant reduction in the vascular endothelial growth factor (VEGF) secretion level and production/activity of matrix metalloproteinases (MMP-2 and MMP-9) in the studied cells. The flow cytometry analysis indicated that MPS suppressed growth of MCF-7 and MDA-MB-231 cells at G0/G1 and S phases, respectively. Our results indicated that the induction of cell cycle arrest was correlated with the obvious changes in expression of p21, p27 and p53. According to the DNA fragmentation assay, MPS caused apoptosis in both cell lines, which confirms the results obtained with the growth assay. Moreover, the compound-mediated apoptosis accompanied with the increase in the Bax/Bcl-2 ratio and caspase-3 and -9 activities. Molecular docking results indicated that the MPS compound can surprisingly bind to VEGF and VEGF receptors and interacts with their critical amino acids. Finally, compounds with anticancer inhibitory activity (e.g. MPS) are abundant in nature and can be obtained from several sources. So, our data can be clinically developed for treating angiogenesis and cancer significantly.
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http://dx.doi.org/10.1016/j.biopha.2017.06.013DOI Listing
September 2017

Differential α-amylase/α-glucosidase inhibitory activities of plant-derived phenolic compounds: a virtual screening perspective for the treatment of obesity and diabetes.

Food Funct 2017 May;8(5):1942-1954

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Recently, due to their biological properties, polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for diabetes mellitus. Inhibition of α-amylase and α-glucosidase enzymes using natural products (especially polyphenols) is a novel oral policy to regulate carbohydrate metabolism and hyperglycemia. The present study aims to evaluate the α-amylase and α-glucosidase inhibitory activity of 26 polyphenols using molecular docking and virtual screening studies. The results speculate that among selected compounds caffeic acid, curcumin, cyanidin, daidzein, epicatechin, eridyctiol, ferulic acid, hesperetin, narenginin, pinoresinol, quercetin, resveratrol and syringic acid can significantly inhibit the α-glucosidase enzyme. In addition, catechin, hesperetin, kaempferol, silibinin and pelargonidin are potent α-amylase inhibitors. Therefore the primary structure of polyphenols can change the inhibitory effect versus the α-amylase and α-glucosidase enzymes. Finally, we speculate that consumption of polyphenol-rich functional foods (by considering the best dose of each compound and assessing their possible side effects) in diabetic patients may be useful for regulating carbohydrate metabolism and related disorders. The findings of the current study may also shed light on a way of generating a new class of amylase/glucosidase inhibitors that will discriminately inhibit the on-target enzymes with negligible undesired off-target side effects.
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http://dx.doi.org/10.1039/c7fo00220cDOI Listing
May 2017

Anti-angiogenic potential of trypsin inhibitor purified from Cucumis melo seeds: Homology modeling and molecular docking perspective.

Int J Biol Macromol 2017 Mar 10;96:118-128. Epub 2016 Dec 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Melons have a good source of protease inhibitors. Its fruit and seeds have been used as a traditional medicine. However, its effects on angiogenesis and mechanism of its action remain elusive. Herein trypsin inhibitor from aqueous extract of C. melo seeds (TICMS) was purified. Its effects on different steps of angiogenesis were evaluated. Also, we examined its effects on migration and angiogenesis of endothelial cells. Three dimensional model of TICMS protein was accurately built in which TICMS docked to αβ integrin and VEGFR1. Electrophoresis analysis of the purified protein revealed a single band with a molecular mass of about 3kDa. Treatment with TICMS at six doses resulted in a significant decrease of endothelial cell proliferation with an IC value of about 20μg/ml. Tubulogenesis assay revealed that a dose dependent anti-angiogenic activity of TICMS (5-40μg/ml). Also, TICMS had inhibitory effects on VEGF, MMP-2 and MMP-9 secretion. Our docking result speculated that TICMS could bind to the cleft between the αβ integrin and it able to decrease the activity of this receptor. The TICMS was also able to interact with VEGFR1 receptor, but with low probability. Based on our study, TICMS could be used as a specific angiogenesis inhibitor.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.12.027DOI Listing
March 2017

Plant Cell Cancer: May Natural Phenolic Compounds Prevent Onset and Development of Plant Cell Malignancy? A Literature Review.

Molecules 2016 Aug 23;21(9). Epub 2016 Aug 23.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714967346, Iran.

Phenolic compounds (PCs) are known as a chemically diverse category of secondary and reactive metabolites which are produced in plants via the shikimate-phenylpropanoid pathways. These compounds-ubiquitous in plants-are an essential part of the human diet, and are of considerable interest due to their antioxidant properties. Phenolic compounds are essential for plant functions, because they are involved in oxidative stress reactions, defensive systems, growth, and development. A large body of cellular and animal evidence carried out in recent decades has confirmed the anticancer role of PCs. Phytohormones-especially auxins and cytokinins-are key contributors to uncontrolled growth and tumor formation. Phenolic compounds can prevent plant growth by the endogenous regulation of auxin transport and enzymatic performance, resulting in the prevention of tumorigenesis. To conclude, polyphenols can reduce plant over-growth rate and the development of tumors in plant cells by regulating phytohormones. Future mechanistic studies are necessary to reveal intracellular transcription and transduction agents associated with the preventive role of phenolics versus plant pathological malignancy cascades.
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http://dx.doi.org/10.3390/molecules21091104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274315PMC
August 2016

Efficient differentiation of human embryonic stem cells toward dopaminergic neurons using recombinant LMX1A factor.

Mol Biotechnol 2015 Feb;57(2):184-94

Department of Molecular Systems Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Direct differentiation of dopaminergic (DA) neurons from human pluripotent stem cells (hPSCs) in the absence of gene manipulation is the most desired alternative to clinical treatment of Parkinson disease. Protein transduction-based methods could be efficient, safe approaches to enhance direct differentiation of human embryonic stem cells (hESCs) to DA neurons. In the present study, we compared the differentiation efficiency of DA neurons from hESCs with and without the application of LIM homeobox transcription factor 1 alpha (LMX1A), a master regulatory protein in the development of the midbrain neurons and SHH proteins. The results obtained revealed that the treatment of hESCs with recombinant LMX1A (rLMX1A) protein along with dual SMAD inhibition led to higher expression of LMX1B, LMX1A, FOXA2, PITX3, EN1, and WNT1 effector endogenous genes and two-fold expression of PITX3. Moreover, the highest expression level of PITX3 and TH was observed when rLMX1A was added to the induction medium supplemented with SHH. To our best knowledge, this is the first report demonstrating the application of TAT-LMX1A recombinant protein to enhance hESC differentiation to DA as shown by the expression of DA specific makers. These findings pave the way for enhancing the differentiation of hESCs to DA neurons safely and efficiently without genetic modification.
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http://dx.doi.org/10.1007/s12033-014-9814-5DOI Listing
February 2015
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