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Jung H.A.,Pukyong National University | Oh S.H.,Korean BioInformation Center | Choi J.S.,Pukyong National University | Choi J.S.,Dong - Eui University
Bioorganic and Medicinal Chemistry Letters | Year: 2010

In our consecutive research on an anti-AD remedy derived from maritime plants, the BACE1 inhibitory activities of Eisenia bicyclis and its isolated phlorotannins were evaluated. The E. bicyclis extract and its fractions exhibited predominant BACE1 inhibition. With the exception of phloroglucinol (1), all test phlorotannins isolated from the most active EtOAc soluble fraction, showed significant and non-competitive inhibition against BACE1:dioxinodehydroeckol (2, IC50 = 5.35 μM; Ki = 8.0); eckol (3, IC50 = 12.20 μM; Ki = 13.9); phlorofurofucoeckol-A (4, IC50 = 2.13 μM; Ki = 1.3); dieckol (5, IC50 = 2.21 μM; Ki = 1.5); triphloroethol A (6, IC50 = 11.68 μM; Ki = 12.1); 7-phloroethol (7, IC50 = 8.59 μM; Ki = 7.2). In addition, plausible protein-ligand interactions of 3, 4, and 5 were similar and may occur primarily through the TYR132 and THR133 of BACE1 via molecular docking simulations (autodock 4.0 and fred 2.0 programs). As a result, the E. bicyclis extract and the phlorotannins contained therein would clearly have beneficial use in the development of therapeutic and preventive agents for AD and suggest potential guidelines for the design of BACE-selective inhibitors. © 2010 Elsevier Ltd. All rights reserved. Source


Choi J.S.,Pukyong National University | Ali M.Y.,Pukyong National University | Jung H.A.,Chonbuk National University | Oh S.H.,Korean BioInformation Center | And 2 more authors.
Journal of Ethnopharmacology | Year: 2015

Ethnopharmacologic relevance: Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugarlowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine. Materials and methods: In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO--mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation. Results: The Coptis alkaloids 1-4 exhibited remarkable inhibitory activities against PTP1B with the IC50 values of 16.43, 24.19, 28.14, and 51.04 μM, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO--mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using the Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=-6.7 to -7.8 kcal/mol; Fred 2.0=-59.4 to -68.2 kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme. Conclusion: Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO--mediated protein tyrosine nitration, and thus hold promise as therapeutic agents for the treatment of diabetes and related disease. © 2015 Elsevier Ireland Ltd. All rights reserved. Source


Lee C.M.,Pukyong National University | Jung H.A.,Chonbuk National University | Oh S.H.,Korean BioInformation Center | Park C.H.,Daegu Haany University | And 3 more authors.
Archives of Pharmacal Research | Year: 2015

Aldose reductase (AR) is a key enzyme in the polyol pathway that is strongly implicated in the pathogenesis of diabetic complications. AR inhibitors have been proposed as therapeutic agents for diabetic complications through suppression of sorbitol formation and accumulation. In this study, we evaluated whether two major compounds of Corni Fructus, loganin and 7-O-galloyl-d-sedoheptulose, had an inhibitory effect on diabetic complications through AR inhibition. Because the iridoid glycoside loganin and the low-molecular-weight polyphenol 7-O-galloyl-d-sedoheptulose showed marginal inhibitory activities against rat lens AR (RLAR) and human recombinant AR (HRAR) in inhibition assays, we performed enzyme kinetic analyses and molecular simulation of the interaction of these two compounds with AR to further investigate their potential as inhibitors of diabetic complications. In kinetic analysis using Lineweaver-Burk plots and Dixon plots, loganin and 7-O-galloyl-d-sedoheptulose were both mixed inhibitors of RLAR with inhibition constants (K i) of 27.99 and 128.68 μÎœ, respectively. Moreover, molecular docking simulation of both compounds demonstrated negative binding energies (Autodock 4.0 = -6.7; -7.5 kcal/mol; Fred 2.0 = -59.4; -63.2 kcal/mol) indicating a high affinity and tight binding capacity for the active site of the enzyme. Iridoid nucleus and aromatic ring systems and glycoside and sedoheptulose moieties were found to bind tightly to the specificity pocket and the anion binding pocket in RLAR through Phe123, His111, Trp21, Tyr49, His111, and Trp112 residues. Our results clearly indicate that loganin and 7-O-galloyl-d-sedoheptulose have great promise for the treatment of diabetic complications through inhibition of AR. © The Pharmaceutical Society of Korea 2014. Source


Islam M.N.,Mawlana Bhashani Science and Technology University | Choi R.J.,University of Cambridge | Jung H.A.,Chonbuk National University | Oh S.H.,Korean BioInformation Center | Choi J.S.,Pukyong National University
Archives of Pharmacal Research | Year: 2016

Caffeoylquinic acids, flavonoids, and coumarins isolated from Artemisia capillaris have recently emerged as therapeutic candidates for diabetes and diabetic complications; however, there have been very few studies of the anti-diabetic potential of polyacetylenes. In the present study, we investigated the anti-diabetic potential of two polyacetylenes isolated from A. capillaris, namely capillin and capillinol by investigating their ability to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and rat lens aldose reductase (RLAR). Capillin displayed potent inhibitory activity against α-glucosidase, PTP1B, and RLAR, while capillinol showed moderate inhibitory activity against α-glucosidase and PTP1B at the concentrations tested. In addition, a kinetic study revealed that capillin inhibited α-glucosidase and RLAR in a noncompetitive manner, while inhibited PTP1B in a mixed-type manner. Capillinol inhibited α-glucosidase and PTP1B in a mixed-type manner. Docking simulations of these compounds demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B, indicating that these polyacetylenes have a high affinity and tight binding capacity for the active site of the enzyme. Furthermore, capillin dose-dependently inhibited peroxynitrite (ONOO-)-mediated tyrosine nitration. The results clearly demonstrate the promising potential of capillin and capillinol as therapeutic interventions for the management of diabetes as well as diabetes-associated complications. © The Pharmaceutical Society of Korea 2016. Source


Li S.,New York Medical College | Tighe S.W.,University of Vermont | Nicolet C.M.,University of Southern California | Grove D.,Pennsylvania State University | And 27 more authors.
Nature Biotechnology | Year: 2014

High-throughput RNA sequencing (RNA-seq) greatly expands the potential for genomics discoveries, but the wide variety of platforms, protocols and performance capabilitites has created the need for comprehensive reference data. Here we describe the Association of Biomolecular Resource Facilities next-generation sequencing (ABRF-NGS) study on RNA-seq. We carried out replicate experiments across 15 laboratory sites using reference RNA standards to test four protocols (poly-A-selected, ribo-depleted, size-selected and degraded) on five sequencing platforms (Illumina HiSeq, Life Technologies PGM and Proton, Pacific Biosciences RS and Roche 454). The results show high intraplatform (Spearman rank R > 0.86) and inter-platform (R > 0.83) concordance for expression measures across the deep-count platforms, but highly variable efficiency and cost for splice junction and variant detection between all platforms. For intact RNA, gene expression profiles from rRNA-depletion and poly-A enrichment are similar. In addition, rRNA depletion enables effective analysis of degraded RNA samples. This study provides a broad foundation for cross-platform standardization, evaluation and improvement of RNA-seq. © 2015 Nature America, Inc. Source

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