Showing papers by "Byung Sun Min published in 2017"
TL;DR: This study indicated that the crude extracts of, and bioactive substances from, the roots of D. asper suppress TGM and TLB and could be used as antifungal lead compounds.
38 citations
TL;DR: Investigation of the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B, α-glucosidase, peroxynitrite (ONOO−)-mediated tyrosin nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes indicates that prunin has significant potential as a selective PTP1B inhibitor and may possess anti-Diabetic properties by improving insulin resistance.
Abstract: Prunin is the main flavonoid in Prunus davidiana stems and improves hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats The aim of this study was to investigate the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, peroxynitrite (ONOO−)-mediated tyrosine nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes In addition, a molecular docking simulation was performed to predict specific prunin binding modes during PTP1B inhibition Prunin showed strong inhibitory activity against PTP1B, with an IC50 value of 55 ± 029 µM, and significant inhibitory activity against α-glucosidase, with an IC50 value of 317 ± 212 µM Moreover, a kinetics study revealed that prunin inhibited PTP1B (K
i = 866) and α-glucosidase (K
i = 18956) with characteristics typical of competitive and mixed type inhibitors, respectively Docking simulations showed that prunin selectively inhibited PTP1B by targeting its active site and exhibited good binding affinity, with a docking score of −9 kcal/mol Furthermore, prunin exhibited dose-dependent inhibitory activity against ONOO−-mediated tyrosine nitration and stimulated glucose uptake by decreasing PTP1B expression level in insulin-resistant HepG2 cells These results indicate that prunin has significant potential as a selective PTP1B inhibitor and may possess anti-diabetic properties by improving insulin resistance
34 citations
TL;DR: A new ellagitannin, agritann in, a new flavone glycoside, agriflavone, and another flavone Glycoside with spectroscopic data reported for the first time, along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb, and most of them were found to have moderate inhibitory effects.
34 citations
TL;DR: Findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme‐oxygenase‐1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases.
Abstract: In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.
30 citations
TL;DR: The chemical characterization of Selaginella tamariscina leaves resulted in the isolation of five lignanoside derivatives (1-4 and 6) and one neolignan (5) that were evaluated in terms of their inhibition of NO production in lipopolysaccharide (LPS)-stimulated activity in the macrophage cell line RAW 264.
26 citations
TL;DR: Five new compounds, 10-oxomornigrol F, together with 31 known compounds, were isolated from the twigs of Morus alba (Moraceae) and evaluated by investigating their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophage RAW 264.7 cells.
25 citations
TL;DR: Sesamin was demonstrated to inhibit T cell activation via regulation of MAPK phosphorylation pathway in phorbol 12-myristate 13-acetate (PMA)/A23187-stimulated T cells.
24 citations
TL;DR: The association of the intensity of bioactivity with the arrangement and characterization of the sugar moiety on the flavonoid skeleton is clearly depicted and suggests that prunin is the best fit to the PTP1B active site cavity.
23 citations
TL;DR: It is suggested that SPNA inhibits osteoclastogenesis and bone resorption by inhibiting the AKT/GSK‐3&bgr; signaling pathway and may be a potential candidate compound for the prevention and/or treatment of inflammatory bone loss.
21 citations
TL;DR: Investigation of the PTP1B inhibitors isolated from natural sources confirms that these compounds exhibited potential inhibitory effect on the P TP1B enzyme activity.
21 citations
TL;DR: Two new flavanonol glucoside isomers were isolated from the aerial parts of Agrimonia pilosa Ledeb.
TL;DR: The structures of the isolates were elucidated using spectroscopic analysis, mainly one- and two-dimensional NMR, high resolution-MS, and circular dichroism techniques as well as Mosher's esterification method.
Abstract: Four new lignans, a furofuran lignan medioresinol B (10) and three tetrahydrofuran lignans kobusinol C (16), 7'-methoxy magnostellin A (21), and mangnostellin D (23), along with 19 known lignans, were isolated from the flower buds of Magnolia biondii PAMP. The structures of the isolates were elucidated using spectroscopic analysis, mainly one- and two-dimensional NMR, high resolution-MS, and circular dichroism techniques as well as Mosher's esterification method. The anti-allergic effects of the isolated compounds were evaluated by analyzing the inhibition of interleukin-2 (IL-2) expression in Jurkat T-cells. Compounds 11-14 reduced IL-2 expression in a dose-dependent manner.
TL;DR: Molecular docking results showed that the tested inhibitors 1 and 6 exhibited good binding affinities toward BACE1, with binding energies of -8.8 and -10.3 kcal/mol, respectively.
TL;DR: Findings suggest that 15,16-dihydrotanshinone I (DHTS), as a C1-Ten protein tyrosine phosphatase inhibitor, could provide a novel therapeutic strategy for insulin resistance-associated metabolic syndrome through dual targeting of IRS-1 and AMPK.
Abstract: Insulin resistance causes type 2 diabetes; therefore, increasing insulin sensitivity is a therapeutic approach against type 2 diabetes. Activating AMP-activated protein kinase (AMPK) is an effective approach for treating diabetes, and reduced insulin receptor substrate-1 (IRS-1) protein levels have been suggested as a molecular mechanism causing insulin resistance. Thus, dual targeting of AMPK and IRS-1 might provide an ideal way to treat diabetes. We found that 15,16-dihydrotanshinone I (DHTS), as a C1-Ten protein tyrosine phosphatase inhibitor, increased IRS-1 stability, improved glucose tolerance and reduced muscle atrophy. Identification of DHTS as a C1-Ten inhibitor revealed a new function of C1-Ten in AMPK inhibition, possibly through regulation of IRS-1. These findings suggest that C1-Ten inhibition by DHTS could provide a novel therapeutic strategy for insulin resistance-associated metabolic syndrome through dual targeting of IRS-1 and AMPK.
TL;DR: The results support the use of triterpenoids in traditional medicine for prevention and treatment of diabetes and cancer.
Abstract: Recently, PTP1B inhibitors have become the frontier as possible targeting for anti-cancer and anti-diabetic drugs. Twelve triterpenoids from the aerial parts of Agrimonia pilosa were investigated for PTP1B inhibitory and cytotoxic activities. In the results, compounds 3 (IC50 = 0.50 μM) and 7 (IC50 = 5.88 μM) were found to possess very powerful inhibitory activity against the PTP1B enzyme, comparable to the positive control ursolic acid (IC50 = 6.60 μM). In addition, compounds 1, 2, 4, and 10‒12 showed potent inhibitory effects against PTP1B, with an IC50 range of 13.48‒14.98 μM. In the kinetic assay of the PTP1B enzyme, compounds 1 and 2 were noncompetitive, whereas 7 and 11 showed a mixed type. In the docking analysis, the results showed that different residues of PTP1B interacted with twelve triterpenoids. Furthermore, compounds 6 (IC50 = 3.65 μM) and 12 (IC50 = 1.21 μM) displayed strong cytotoxic effects against the HeLa cell line. Compounds 2 (IC50 = 16.06 μM) and 4 (IC50 = 14.73 μM) showed moderate cytotoxic activities against the HeLa cell line. Compound 2 exhibited comprehensive cytotoxicity against the HL-60 (IC50 = 45.53 μM) and MCF-7 (IC50 = 34.21 μM) cell lines. These results support the use of triterpenoids in traditional medicine for prevention and treatment of diabetes and cancer.
TL;DR: Two new phloroglucinols (7 and 10) and 12 known derivatives (1-6, 8-9, and 11-14) were isolated from the roots of Dryopteris crassirhizoma and their chemical structures were elucidated by various spectroscopic methods.
TL;DR: It is reported for the first time the isolation of erythrofordin V from a natural source and that of the remaining eight known diterpenoids (4-5, 8-13) from E. fordii.
TL;DR: It is demonstrated that 3-ANE inhibited the vascular endothelial growth factor (VEGF)-mediated proliferation, migration, invasion, and capillary-like tube formation of human umbilical vascular endothelium cells (HUVECs), without inducing apoptosis, the first evidence that3-ANE inhibits tumor angiogenesis by inhibiting the VEGF-mediated eNOS activation and NO production.
Abstract: Nara Tae 1 , Tran Manh Hung 2, 4 , Okwha Kim 1 , Namho Kim 1 , Suhyun Lee 1 , Sunghun Na 3 , Byung-Sun Min 2 and Jeong-Hyung Lee 1 1 Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Republic of Korea 2 College of Pharmacy, Catholic University of Daegu, Daegu, Republic of Korea 3 Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea 4 Current/Present address: Biomedical Science Department, VNUK Institute for Research & Executive Education, The University of Da Nang, Da Nang, Vietnam Correspondence to: Byung-Sun Min, email: bsmin@cu.ac.kr Jeong-Hyung Lee, email: jhlee36@kangwon.ac.kr Keywords: angiogenesis, cassaine diterpene alkaloid, VEGF, eNOS, HSP90 Received: April 15, 2017 Accepted: August 26, 2017 Published: September 28, 2017 ABSTRACT Angiogenesis is one of the hallmarks of cancer, playing an essential role in tumor growth, invasion, and metastasis. 3β-Acetyl-nor-erythrophlamide (3-ANE), a cassaine diterpene alkaloid compound from Erythrophleum fordii , exerts various pharmacological effects, including antitumor activity. However, the effects of 3-ANE on tumor angiogenesis and its potential molecular mechanism are still unknown. Here, we demonstrated that 3-ANE inhibited the vascular endothelial growth factor (VEGF)-mediated proliferation, migration, invasion, and capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs), without inducing apoptosis. We also found that 3-ANE blocked angiogenesis in vivo , and suppressed tumor angiogenesis and human lung adenocarcinoma growth in the xenograft tumor model. Furthermore, we showed that 3-ANE blocked VEGF-mediated endothelial nitric oxide synthase (eNOS) phosphorylation, vascular permeability and NO production in HUVECs, via disrupting the VEGF-induced association of eNOS and heat-shock protein 90 (HSP90). Our studies therefore provide the first evidence that 3-ANE inhibits tumor angiogenesis by inhibiting the VEGF-mediated eNOS activation and NO production, and 3-ANE could be a potential candidate in angiogenesis-related disease therapy.
TL;DR: Results suggest that α-methyl artoflavanocoumarin from J. chinensis has therapeutic potential in T2DM by inhibiting PTP1B and activating insulin signaling pathways.
Abstract: Diabetes mellitus is one of the greatest global health issues and much research effort continues to be directed toward identifying novel therapeutic agents. Insulin resistance is a challenging integrally related topic and molecules capable of overcoming it are of considerable therapeutic interest in the context of type 2 diabetes mellitus (T2DM). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling transduction and is regarded a novel therapeutic target in T2DM. Here, we investigated the inhibitory effect of α-methyl artoflavanocoumarin (MAFC), a natural flavanocoumarin isolated from Juniperus chinensis, on PTP1B in insulin-resistant HepG2 cells. MAFC was found to potently inhibit PTP1B with an IC50 of 25.27 ± 0.14 µM, and a kinetics study revealed MAFC is a mixed type PTP1B inhibitor with a K
i
value of 13.84 µM. Molecular docking simulations demonstrated MAFC can bind to catalytic and allosteric sites of PTP1B. Furthermore, MAFC significantly increased glucose uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells, down-regulated the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307), and dose-dependently enhanced the protein levels of IRS-1, phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and ERK1. These results suggest that MAFC from J. chinensis has therapeutic potential in T2DM by inhibiting PTP1B and activating insulin signaling pathways.
TL;DR: This finding indicated that tetracyclic triterpenoids isolated from E. utilis may have potential beneficial effects for the treatment of cancer.
TL;DR: This is the first study to investigate the significant anti-tumor properties of isolated compounds from the stem bark of S. obassia as well as identify seven known compounds that exhibited cytotoxic activity against breast cancer cell line MCF-7.
Abstract: Cancer is a major public health burden in both developed and developing countries. Plant-derived compounds have played an important role in the development of useful anti-cancer agents. The current study was designed to evaluate the cytotoxic activity of chemical compounds from the stem bark of Styrax obassia. Seven known compounds (1-7) were isolated and identified. Compound 2 exhibited cytotoxic activity against the breast cancer cell line MCF-7 with an IC5₅₀ of 27.9 μM, followed by the human cervical cancer cell line Hela with an IC₅₀ of 23.3 μM, and the human promyelocytic leukemia cell line HL-60 with an IC₅₀ of 47.8 RM. Compound 7 exhibited cytotoxicity against Hela cells with an ICso of 16.8 pM, followed by MCF-7 cells with an IC₅₀ of 53.5 μM. This is the first study to investigate the significant anti-tumor properties of isolated compounds from the stem bark of S. obassia.
TL;DR: Four compounds, (-)-parthenolide (2), eudesm-4(15)-eno-1β,6α-diol (5), biondinin D (12), and tiliroside (16), showed cytotoxicity against Jurkat T cells and exhibited cytot toxicity against the human cervical cancer HeLa cell line, the human breast cancer MCF-7, and human promyelocytic leukemia HL-60 cell lines.
Abstract: Ten sesquiterpenoids (1-10) and six phenylpropanoid derivatives (11-16) were isolated from the flower buds of Magnolia biondii Pamp. Their structures were determined by 1D- and 2D-NMR spectroscopy,...
TL;DR: The isolation of the MeOH extract from the flower bud of Magnolia biondii Pamp led to eleven neoglignan derivatives, which were tested for anti-allergic effects using IL-2 inhibitory assay in Jurkat T cells.
Abstract: − The isolation of the MeOH extract from the flower bud of Magnolia biondii Pamp. using various column chromatographies and HPLC led to eleven neoglignan derivatives (1 11). Their structures were mainly determined by 1D and 2D NMR spectral data analysis and physiological methods. The isolated compounds (1 11) were tested for anti-allergic effects using IL-2 inhibitory assay in Jurkat T cells.
TL;DR: Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations.
Abstract: S-1 (TS-1®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of SDT on the pharmacokinetics of S-1. Sprague-Dawley rats were pretreated with a single dose or repeated doses of SDT for seven consecutive days (1200 mg/kg/day). After the completion of pretreatment with SDT, S-1 was orally administered and plasma concentrations of tegafur, its active metabolite 5-FU, and gimeracil were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A population pharmacokinetic model was developed to evaluate the effect of SDT on pharmacokinetics of tegafur and 5-FU. Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations. Population pharmacokinetic modeling also showed the enhanced elimination of 5-FU in the SDT-pretreated group. Repeated doses of SDT may inhibit the absorption of gimeracil, an inhibitor of 5-FU metabolism, resulting in enhanced elimination of 5-FU and decrease its plasma level.