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Timeline of Sang Hyun Sung

2019
Mar
01
Published new article




Article

Multiple Targets of 3-Dehydroxyceanothetric Acid 2-Methyl Ester to Protect Against Cisplatin-Induced Cytotoxicity in Kid...

Published: 01 March 2019 by MDPI in Molecules

doi: 10.3390/molecules24050878

Chronic exposure to cisplatin, a potent anticancer drug, causes irreversible kidney damage. In this study, we investigated the protective effect and mechanism of nine lupane- and ceanothane-type triterpenoids isolated from jujube (Ziziphus jujuba Mill., Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. Cisplatin-induced LLC-PK1 cell death was most significantly reduced following treatment with 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME). Additionally, apoptotic cell death was significantly reduced. Expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 was markedly suppressed by 3DC2ME, indicating inhibition of the MAPK pathway. Treatment with 3DC2ME also significantly reduced expression of active caspase-8 and -3, Bcl-2-associated X protein (Bax), and B cell lymphoma 2 (Bcl-2), indicating the inhibition of apoptosis pathways in the kidneys. We also applied the network pharmacological analysis and identified multiple targets of 3DC2ME related to MAPK signaling pathway and apoptosis.

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2019
Feb
15
Published new article




Article

Expedient Synthesis of Alphitolic Acid and Its Naturally Occurring 2-O-Ester Derivatives

Published: 15 February 2019 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.8b00986

The expedient synthesis of alphitolic acid (1) as well as its natural C-3-epimer and 2-O-ester derivatives was accomplished in a few steps from the readily commercially available betulin (9). A Rubottom oxidation delivered an α-hydroxy group in a stereo- and chemoselective manner. The diastereoselective reduction of the α-hydroxy ketone was key to accessing the 1,2-diol moiety of this class of natural products. Our concise and stereoselective synthetic protocol allowed the gram-scale synthesis of these natural products, which will facilitate future biological evaluations.

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2019
Jan
24
Published new article




Article

Lignan Dimers from Forsythia viridissima Roots and Their Antiviral Effects

Published: 24 January 2019 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.8b00590

Six new dimeric lignans (1–6) and one new lignan glycoside (16) were isolated from Forsythia viridissima roots along with nine known lignans (7–15). Spectroscopic analyses and chemical methods were used to determine these new structures and their absolute configurations. Among these compounds, dimatairesinol (1) and viridissimaols A–E (2–6) were assigned as dimers of dibenzylbutyrolactone analogues. Furthermore, the isolated compounds were evaluated for their antiviral activities against coxsackievirus B3 (CVB3) and human rhinovirus 1B (HRV1B). In these tests, compounds 12 and 15 showed antiviral effects against CVB3 infection with IC50 values of 15.4 and 36.4 μM, respectively, while 2, 3, 8, and 9 showed activities against HRV1B with IC50 values of 45.7, 47.5, 13.0, and 43.2 μM, respectively.

0 Reads | 1 Citations
2019
Jan
02
Published new article




Article

Two complete chloroplast genome sequences and intra-species diversity for Rehmannia glutinosa (Orobanchaceae)

Published: 02 January 2019 by Informa UK Limited in Mitochondrial DNA Part B

doi: 10.1080/23802359.2018.1545529

Rehmannia glutinosa is a plant used as traditional medicine for its various tonic effects in Korea and China. In this study, chloroplast genomes of two R. glutinosa were completed by de novo assembly using whole-genome Illumina sequence data. The length of chloroplast genomes of R. glutinosa collected from China and Korea was 153,680 bp and 153,499 bp, respectively. A total of 114 coding regions were predicted in both R. glutinosa including 80 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. We identified abundant intra-species diversity of 87 InDels and 147 SNPs, among three R. glutinosa chloroplast genome sequences including one from GenBank. The phylogenetic analysis showed that these R. glutinosa were closely clustered with related Rehmannia species, separated from other Orobanchaceae and Scrophulariaceae species.

0 Reads | 1 Citations
2018
Dec
19
Published new article




Article

Screening of cytotoxic or cytostatic flavonoids with quantitative Fluorescent Ubiquitination-based Cell Cycle Indicator-...

Published: 19 December 2018 by The Royal Society in Royal Society Open Science

doi: 10.1098/rsos.181303

The Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) system can be used not only to study gene expression at a specific cell cycle stage, but also to monitor cell cycle transitions in real time. In this study, we used a single clone of FUCCI-expressing HeLa cells (FUCCI-HeLa cells) and monitored the cell cycle in individual live cells over time by determining the ratios between red fluorescence (RF) of RFP-Cdt1 and green fluorescence (GF) of GFP-Geminin. Cytotoxic and cytostatic compounds, the latter of which induced G2 or mitotic arrest, were identified based on periodic cycling of the RF/GF and GF/RF ratios in FUCCI-HeLa cells treated with anti-cancer drugs. With this cell cycle monitoring system, ten flavonoids were screened. Of these, apigenin and luteolin, which have a flavone backbone, were cytotoxic, whereas kaempferol, which has a flavonol backbone, was cytostatic and induced G2 arrest. In summary, we developed a system to quantitatively monitor the cell cycle in real time. This system can be used to identify novel compounds that modulate the cell cycle and to investigate structure–activity relationships.

0 Reads | 1 Citations
2018
Nov
23
Published new article




Article

A new phenolic compound from Phedimus middendorffianus with antiproliferative activity

Published: 23 November 2018 by Informa UK Limited in Natural Product Research

doi: 10.1080/14786419.2018.1527830

A new phenolic compound (1) and together with 12 known compounds–eight flavonoids (2 ∼ 9), two phenolic compounds (10 and 11) and two benzoic acid (12 and 13)–were isolated from Phedimus middendorffianus (Maxim.). The structures of all compound were determined on the basis of spectroscopic (MS and NMR) analyses. Compounds 4, 5, 7 and 11 ∼ 13 were showed anti-proliferative activities against MCF-7 than PC-3 cell line. Also compound 12 and 13 showed the significant cytotoxic activities against two cancer cell lines, PC-3 and MCF-7.

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2018
Nov
07
Published new article






Comprehensive mass spectrometry-guided plant specialized metabolite phenotyping reveals metabolic diversity in the cosmo...

Published: 07 November 2018 by Cold Spring Harbor Laboratory in bioRxiv

doi: 10.1101/463620

Plants produce a myriad of specialized metabolites to overcome their sessile habit and combat biotic as well as abiotic stresses. Evolution has shaped specialized metabolite diversity, which drives many other aspects of plant biodiversity. However, until recently, large-scale studies investigating specialized metabolite diversity in an evolutionary context have been limited by the impossibility to identify chemical structures of hundreds to thousands of compounds in a time-feasible manner. Here, we introduce a workflow for large-scale, semi-automated annotation of specialized metabolites, and apply it for over 1000 metabolites of the cosmopolitan plant family Rhamnaceae. We enhance the putative annotation coverage dramatically, from 2.5 % based on spectral library matches alone to 42.6 % of total MS/MS molecular features extending annotations from well-known plant compound classes into the dark plant metabolomics matter. To gain insights in substructural diversity within the plant family, we also extract patterns of co-occurring fragments and neutral losses, so-called Mass2Motifs, from the dataset; for example, only the Ziziphoid clade developed the triterpenoid biosynthetic pathway, whereas the Rhamnoid clade predominantly developed diversity in flavonoid glycosides, including 7-O-methyltransferase activity. Our workflow provides the foundations towards the automated, high-throughput chemical identification of massive metabolite spaces, and we expect it to revolutionize our understanding of plant chemoevolutionary mechanisms.

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2018
Nov
01
Published new article




Article

Chemical and genomic diversity of six Lonicera species occurring in Korea

Published: 01 November 2018 by Elsevier BV in Phytochemistry

doi: 10.1016/j.phytochem.2018.07.012

Lonicera spp. (Caprifoliaceae) are important not only as a common medicinal herb in East Asia but also as one of the most problematic invasive species in North America. In the present study, we performed a systemic analysis of genomic and chemical diversity among six Lonicera species occurring in Korea, L. japonica, L. maackii, L. insularis, L. sachalinensis, L. praeflorens, and L. vesicaria, using chloroplast DNA whole genome shotgun (WGS) sequencing and LC–MS analyses. The phylogenetic and phylochemical relationships did not coincide with each other, but partial consistency could be found among them. InDel-based cDNA marker for authentication was developed based on the genome sequences. Flavonoids, iridoids, and organic acids were identified in the LC–MS analyses, and their inter-species distribution and localization were also revealed.

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2018
Aug
14
Published new article




Article

Targeted Isolation of Neuroprotective Dicoumaroyl Neolignans and Lignans from Sageretia theezans Using in Silico Molecul...

Published: 14 August 2018 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.8b00292

The integration of LC–MS/MS molecular networking and in silico MS/MS fragmentation is an emerging method for dereplication of natural products. In the present study, a targeted isolation of natural products using a new in silico-based annotation tool named Network Annotation Propagation (NAP) is described. NAP improves accuracy of in silico fragmentation analyses by reranking candidate structures based on the network topology from MS/MS-based molecular networking. Annotation for the MS/MS spectral network of the Sageratia theezans twig extract was performed using NAP, and most molecular families within the network, including the known triterpenoids 1–7, could be putatively annotated, without relying on any previous reports of molecules from this species. Based on the in silico dereplication results, molecules were prioritized for isolation. In total, six dicoumaroyl 8-O-4′ neolignans (8–13) and three dicoumaroyl lignans (14–16) were isolated from the twigs of S. theezans and structurally characterized by spectroscopic analyses. Isolates were evaluated for their neuroprotective activity, and compounds 14–16 showed potent protective effects against glutamate-induced oxidative stress in mouse HT22 cells at a concentration of 12.5 μM.

0 Reads | 2 Citations
2018
Aug
06
Published new article




Article

Identification of candidate UDP-glycosyltransferases involved in protopanaxadiol-type ginsenoside biosynthesis in Panax ...

Published: 06 August 2018 by Springer Nature in Scientific Reports

doi: 10.1038/s41598-018-30262-7

Ginsenosides are dammarane-type or triterpenoidal saponins that contribute to the various pharmacological activities of the medicinal herb Panax ginseng. The putative biosynthetic pathway for ginsenoside biosynthesis is known in P. ginseng, as are some of the transcripts and enzyme-encoding genes. However, few genes related to the UDP-glycosyltransferases (UGTs), enzymes that mediate glycosylation processes in final saponin biosynthesis, have been identified. Here, we generated three replicated Illumina RNA-Seq datasets from the adventitious roots of P. ginseng cultivar Cheongsun (CS) after 0, 12, 24, and 48 h of treatment with methyl jasmonate (MeJA). Using the same CS cultivar, metabolomic data were also generated at 0 h and every 12–24 h thereafter until 120 h of MeJA treatment. Differential gene expression, phylogenetic analysis, and metabolic profiling were used to identify candidate UGTs. Eleven candidate UGTs likely to be involved in ginsenoside glycosylation were identified. Eight of these were considered novel UGTs, newly identified in this study, and three were matched to previously characterized UGTs in P. ginseng. Phylogenetic analysis further asserted their association with ginsenoside biosynthesis. Additionally, metabolomic analysis revealed that the newly identified UGTs might be involved in the elongation of glycosyl chains of ginsenosides, especially of protopanaxadiol (PPD)-type ginsenosides.

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2018
Jul
03
Published new article




Article

The complete chloroplast genome sequence of Korean Lonicera japonica and intra-species diversity

Published: 03 July 2018 by Informa UK Limited in Mitochondrial DNA Part B

doi: 10.1080/23802359.2018.1502637

Lonicera japonica is a traditional medicinal plant well known for its anti-inflammatory effect. The complete chloroplast genome sequence of L. japonica collected from Korea was obtained by de novo assembly using whole genome sequence data. The chloroplast genome is 155,060 bp in length, containing 88,853 bp in a large single copy (LSC), 18,653 bp in a small single copy (SSC) and 23,777 bp in a pair of inverted repeats (IRs). A total of 112 genes including 78 protein-coding genes and 34 structural RNA genes were identified. The sequence comparison of two L. japonica collected from Korea and China revealed 48 single nucleotide polymorphisms (SNPs) and 45 insertions/deletions (InDels). In addition, phylogenetic analysis represented intraspecific diversity within L. japonica species collected in Korea and China.

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2018
Jul
03
Published new article




Article

The complete chloroplast genome sequence of Magic Lily (Lycoris squamigera)

Published: 03 July 2018 by Informa UK Limited in Mitochondrial DNA Part B

doi: 10.1080/23802359.2018.1527193

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2018
Jul
03
Published new article




Article

The complete chloroplast genome sequence of Hosta capitata (Koidz.) Nakai (Asparagaceae)

Published: 03 July 2018 by Informa UK Limited in Mitochondrial DNA Part B

doi: 10.1080/23802359.2018.1511858

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2018
Jun
15
Published new article




Article

Betulin Suppresses Osteoclast Formation via Down-Regulating NFATc1

Published: 15 June 2018 by MDPI in Journal of Clinical Medicine

doi: 10.3390/jcm7060154

Osteoporosis is a disease characterized by osteoclast-mediated low bone mass. The modulation of osteoclasts is important for the prevention or therapeutic treatment of loss of bone mass. Osteoclasts, which are bone-resorbing multinucleated cells, are differentiated from the hematopoietic stem cell monocyte/macrophage lineage by Receptor activator of nuclear factor kappa-B ligand (RANKL) expressed from osteoblasts and stromal cells. RANKL signaling ultimately activates nuclear factor of activated T Cells 1 (NFATc1), which is a master transcription factor in osteoclastogenesis. Betulin, a lupine type pentacyclic triterpenoid, was isolated from the bark of Betula platyphylla. Betulin inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1. Betulin may serve as a useful structural scaffold in the therapeutic agent development to prevention/treatment the osteoclast-mediated bone disorder.

0 Reads | 1 Citations
2018
May
25
Published new article




Article

Genome and evolution of the shade-requiring medicinal herb Panax ginseng

Published: 25 May 2018 by Wiley in Plant Biotechnology Journal

doi: 10.1111/pbi.12926

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane‐type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome‐scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics‐assisted breeding or metabolic engineering.

0 Reads | 3 Citations
2018
May
10
Published new article




Article

Simultaneous Determination and Stability Test of Two Phthalic Anhydride Derivatives, Senkyunolide A and Z -Ligustilide, ...

Published: 10 May 2018 by Wiley in Bulletin of the Korean Chemical Society

doi: 10.1002/bkcs.11471

Cnidium rhizome from Cnidium officinale Makino and Ligusticum chuanxiong Hort (Umbelliferae) is traditionally used to treat pain in East Asian countries. Senkyunolide A and Z‐ligustilide are phthalic anhydride derivatives that are the bioactive components of cnidium rhizome and chemical markers of the two species; they are also susceptible to external stimuli. In this study, we developed a method to identify two chemical markers using high‐performance liquid chromatography (HPLC) with an ultraviolet detector (UVD); the contents of senkyunolide A and Z‐ligustilide in cnidium rhizome from different regions were quantified. The stabilities of the compounds were tested at two different temperatures over 12 months. An HPLC‐UVD system was used to identify and quantify senkyunolide A and Z‐ligustilide in 10 C. officinale samples and 6 L. chuanxiong samples from China and Korea. The long‐term stability of the C. officinale samples in dark conditions at 4 and 25 °C was also tested. The calibration curves for the two chemical markers showed high linearity (R2 = 1.0000), the precision was high (relative standard deviation (RSD) 10% of the compounds degraded after storage at 4 and 25 °C for 6 months. A method was developed to rapidly identify two chemical markers in cnidium rhizome with good linearity, precision, and accuracy using HPLC‐UVD. These markers will be utilized for the quality control or evaluation of herbal preparations containing cnidium rhizome.

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2018
May
02
Published new article




Article

Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in...

Published: 02 May 2018 by Springer Nature in BMC Complementary and Alternative Medicine

doi: 10.1186/s12906-018-2212-y

Terminalia chebula Retz. (Combretaceae) is a traditional herbal medicine that is widely used in the treatment of diabetes, immunodeficiency diseases, and stomach ulcer in Asia. However, the anti-amnesic effect of T. chebula has not yet been investigated. The present study was designed to determine whether T. chebula extract (TCE) alleviates amnesia induced by scopolamine in mice. We also investigated possible mechanisms associated with cholinergic system and anti-oxidant effects. TCE (100 or 200 mg/kg) was orally administered to mice for fourteen days (days 1–14), and scopolamine was intraperitoneally injected to induce memory impairment for seven days (days 8–14). Learning and memory status were evaluated using the Morris water maze. Hippocampal levels of acetylcholine (ACh), acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were measured ex vivo. Levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) in the hippocampus were also examined. In the Morris water maze task, TCE treatment reversed scopolamine-induced learning and memory deficits in acquisition and retention. TCE reduced hippocampal AChE activities and increased ChAT and ACh levels in the scopolamine-induced model. Moreover, TCE treatment suppressed scopolamine-induced oxidative damage by ameliorating the increased levels of ROS, NO, and MDA. These findings suggest that TCE exerts potent anti-amnesic effects via cholinergic modulation and anti-oxidant activity, thus providing evidence for its potential as a cognitive enhancer for amnesia. The online version of this article (10.1186/s12906-018-2212-y) contains supplementary material, which is available to authorized users.

5 Reads | 2 Citations
2018
May
01
Published new article




Article

Anti-inflammatory activity of mulberrofuran K isolated from the bark of Morus bombycis

Published: 01 May 2018 by Elsevier BV in International Immunopharmacology

doi: 10.1016/j.intimp.2017.11.002

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2018
Mar
24
Published new article




Article

Rhamnellosides A and B, ω-Phenylpentaene Fatty Acid Amide Diglycosides from the Fruits of Rhamnella franguloides

Published: 24 March 2018 by MDPI in Molecules

doi: 10.3390/molecules23040752

Two new ω-phenylpentaene fatty acid amide diglycosides, rhamnellosides A (1) and B (2), were isolated from the fruits of Rhamnella franguloides (Rhamnaceae). These compounds were prioritized using LC-MS/MS molecular networking dereplication based on our previous discovery of 2-acetoxy-ω-phenylpentaene fatty acid triglycosides berchemiosides A−C from a phylogenetically related species, Berchemia berchemiifolia. The structures of the isolated compounds were elucidated by spectroscopic analyses in combination with chemical derivatization. The pentaene groups of 1 and 2 were found to have (6E, 8E, 10Z, 12Z, 14E)-geometry, which is the same as that found in berchemioside A.

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2018
Jan
15
Published new article




Article

Anti-cholinesterase Activities of Hydrolysable Tannins and Polyhydroxytriterpenoid Derivatives from Terminalia chebula R...

Published: 15 January 2018 by ACG Publications in Records of Natural Products

doi: 10.25135/rnp.29.17.07.130

0 Reads | 1 Citations
2018
Jan
01
Published new article




Article

Efficient preparation of narcissin from Opuntia ficus-indica fruits by combination of response surface methodology and h...

Published: 01 January 2018 by Medknow in Pharmacognosy Magazine

doi: 10.4103/pm.pm_422_17

Background: Narcissin is well known for their various biological activities. Objective: To recover narcissin from the Opuntia ficus-indica fruits (OFIF), an efficient method was developed by a combination of response surface methodology (RSM) and high-speed countercurrent chromatography (HSCCC). Materials and Methods: Optimization of extraction conditions of narcissin from OFIF was determined using RSM with three-level-three-factor Box-Behnken design (BBD). Then, a rapid and efficient method for the isolation of narcissin from the rich narcissin extracts was developed using HSCCC. Results: Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as extraction time (X1), 6.02 h; solvent to material ratio (X2), 8.16 mL/g; and ethanol concentration (X3), 93.48%. Then, the rich narcissin extracts were separated by HSCCC with a two-phase solvent system composed of n-hexane: ethyl acetate: methanol: water (1.5:5:5:1.5, v/v/v/v) in one step within 60 min. As a result, 12 mg of narcissin was isolated from 100 mg of crude extract with purities of 98.5%, as determined by high-performance liquid chromatography (HPLC). Conclusion: This study can be useful to the development of industrial extraction processes, including further studies concerning the optimal number of sequential steps to enhance the efficacy of a large-scale extraction system.Abbreviations used: BBD: Box-Behnken design; HPLC: High-performance liquid chromatography; HSCCC: High-speed countercurrent chromatography; OFIF: Opuntia ficus-indica fruits; RSM: Response surface methodology

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2018
Jan
01
Published new article




Article

Classficiation of Bupleuri Radix according to Geographical Origins using Near Infrared Spectroscopy (NIRS) Combined with...

Published: 01 January 2018 by The Korean Society of Pharmacognosy (KAMJE) in Natural Product Sciences

doi: 10.20307/nps.2018.24.3.164

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2017
Dec
01
Published new article




Article

Discrimination and Authentication of Eclipta prostrata and E. alba Based on the Complete Chloroplast Genomes

Published: 01 December 2017 by Korean Society of Breeding Science in Plant Breeding and Biotechnology

doi: 10.9787/pbb.2017.5.4.334

0 Reads | 1 Citations
2017
Nov
10
Published new article




Article

Authentication of Zanthoxylum Species Based on Integrated Analysis of Complete Chloroplast Genome Sequences and Metaboli...

Published: 10 November 2017 by American Chemical Society (ACS) in Journal of Agricultural and Food Chemistry

doi: 10.1021/acs.jafc.7b04167

We performed chloroplast genome sequencing and comparative analysis of two Rutaceae species, Zanthoxylum schinifolium (Korean pepper tree) and Z. piperitum (Japanese pepper tree), which are medicinal and culinary crops in Asia. We identified more than 837 single nucleotide polymorphisms and 103 insertions/deletions (InDels) based on a comparison of the two chloroplast genomes and developed seven DNA markers derived from five tandem repeats and two InDel variations that discriminated between Korean Zanthoxylum species. Metabolite profile analysis pointed to three metabolic groups, one with Korean Z. piperitum samples, one with Korean Z. schinifolium samples, and the last containing all the tested Chinese Zanthoxylum species samples, which are considered to be Z. bungeanum based on our results. Two markers were capable of distinguishing among these three groups. The chloroplast genome sequences identified in this study represent a valuable genomics resource for exploring diversity in Rutaceae, and the molecular markers will be useful for authenticating dried Zanthoxylum berries in the marketplace.

0 Reads | 2 Citations
2017
Nov
01
Published new article




Article

Nrf2-Mediated HO-1 Induction and Antineuroinflammatory Activities of Halleridone

Published: 01 November 2017 by Mary Ann Liebert Inc in Journal of Medicinal Food

doi: 10.1089/jmf.2017.3949

Nuclear factor E2-related factor 2 (Nrf2) is the master regulator of antioxidant enzymes and is known to act on the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Few studies have examined the bioactivity of halleridone. Herein, we investigated whether halleridone, which was isolated from the stems of the plant Cornus walteri, could regulate Nrf2-mediated heme oxygenase (HO)-1 expression and prevent intramicroglial inflammation induced by amyloid beta (Aβ)1-42 overexpression. Biochemical and molecular experiments, such as real-time polymerase chain reaction, Western blot analysis, immunocytochemistry, immunofluorescence, and luciferase reporter gene assays, were performed. The results demonstrated that halleridone promoted the upregulation of Nrf2 expression and its translocation to the nucleus, thereby activating antioxidant response element gene transcription and HO-1 expression in murine hippocampal HT22 cells. Additionally, halleridone removed intramicroglial Aβ1-42 and suppressed the production of inflammatory mediators such as interleukin (IL)-1β, IL-6, prostaglandin E2, and nitric oxide (NO) induced by artificially overexpressed Aβ1-42 and decreased pNF-κB accumulation in the nucleus and the expression of inducible NO synthase and cyclooxygenase II in BV-2 cells. In conclusion, halleridone activated Nrf2-mediated HO-1 expression and inhibited Aβ1-42-overexpressed microglial BV-2 cell activation. These observations suggest that halleridone may have therapeutic potential for targeting neurodegeneration through neuroinflammation.

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2017
Oct
06
Published new article




Article

C-Methylated Flavonoid Glycosides from Pentarhizidium orientale Rhizomes and Their Inhibitory Effects on the H1N1 Influe...

Published: 06 October 2017 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.7b00677

Thirteen C-methylated flavonoid glycosides (1–13), along with 15 previously known flavonoids (14–28), were isolated from rhizomes of Pentarhizidium orientale. Among these compounds, matteuorienates D–K (1–8) were obtained as analogues of matteuorienates A–C (14–16), which contain a characteristic 3-hydroxy-3-methylglutaryl (HMG) moiety. The structures of 1–13 were characterized by spectroscopic analysis and chemical derivatization. The isolates were evaluated for their antiviral activities against influenza virus (H1N1), with compounds 21, 22, 23, 25, and 26 showing inhibitory effects (IC50 of 23.9–30.3 μM) against neuraminidases.

0 Reads | 2 Citations
2017
Oct
03
Published new article




Article

Berchemiosides A–C, 2-Acetoxy-ω-phenylpentaene Fatty Acid Triglycosides from the Unripe Fruits of Berchemia berchemiifol...

Published: 03 October 2017 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.7b00602

Three compounds in a new class of 2-acetoxy-ω-phenylpentaene fatty acid triglycosides, berchemiosides A–C (1–3), and a biosynthetically related phenolic glycoside (4) were isolated from the unripe fruits of Berchemia berchemiifolia, along with three flavonoid 5-O-diglycosides (5–7) and three known flavonoids (8–10). Their chemical structures including absolute configurations were determined by spectroscopic analysis in combination with chemical derivatization. The pentaene group of 1 was found to have (6E,8E,10Z,12Z,14E)-geometry, whereas those of 2 and 3 exhibited all-E geometries. The isolated compounds were examined for their cytotoxicity and xanthine oxidase (XO) inhibitory activity; only compound 7 showed weak XO inhibitory activity.

0 Reads | 3 Citations
2017
Oct
01
Published new article




Article

Ceanothane- and lupane-type triterpene esters from the roots of Hovenia dulcis and their antiproliferative activity on H...

Published: 01 October 2017 by Elsevier BV in Phytochemistry

doi: 10.1016/j.phytochem.2017.06.014

Three ceanothane-type and three lupane-type triterpenoids, as well as three known compounds, were isolated from the roots of Hovenia dulcis (Rhamnaceae), based on LC-MS dereplication. The previously undescribed compounds were determined to be 27-O-protocatechuoyl-3-dehydroxyisoceanothanolic acid, 27-O-protocatechuoyl-3-dehydroxycolubrinic acid, 27-O-protocatechuoyl-3-dehydroxyepicolubrinic acid, 27-O-protocatechuoylbetulinic acid, 27-O-p-hydroxybenzoylbetulinic acid, and 27-O-syringoylbetulinic acid by 1D and 2D NMR spectroscopic and HR mass spectrometric data analysis. The isolates were examined for their antiproliferative activity in HSC-T6 hepatic stellate cells; compounds 1, 2, 3, and 6 showed IC50 values in the range of 15-50 μM.

0 Reads | 2 Citations
2017
Sep
14
Published new article




Article

Nrf2-Mediated HO-1 Induction and Antineuroinflammatory Activities of Halleridone.

Published: 14 September 2017 in Journal of Medicinal Food

doi:

Nuclear factor E2-related factor 2 (Nrf2) is the master regulator of antioxidant enzymes and is known to act on the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Few studies have examined the bioactivity of halleridone. Herein, we investigated whether halleridone, which was isolated from the stems of the plant Cornus walteri, could regulate Nrf2-mediated heme oxygenase (HO)-1 expression and prevent intramicroglial inflammation induced by amyloid beta (Aβ)1-42 overexpression. Biochemical and molecular experiments, such as real-time polymerase chain reaction, Western blot analysis, immunocytochemistry, immunofluorescence, and luciferase reporter gene assays, were performed. The results demonstrated that halleridone promoted the upregulation of Nrf2 expression and its translocation to the nucleus, thereby activating antioxidant response element gene transcription and HO-1 expression in murine hippocampal HT22 cells. Additionally, halleridone removed intramicroglial Aβ1-42 and suppressed the production of inflammatory mediators such as interleukin (IL)-1β, IL-6, prostaglandin E2, and nitric oxide (NO) induced by artificially overexpressed Aβ1-42 and decreased pNF-κB accumulation in the nucleus and the expression of inducible NO synthase and cyclooxygenase II in BV-2 cells. In conclusion, halleridone activated Nrf2-mediated HO-1 expression and inhibited Aβ1-42-overexpressed microglial BV-2 cell activation. These observations suggest that halleridone may have therapeutic potential for targeting neurodegeneration through neuroinflammation.

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2017
Aug
28
Published new article




Article

Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes

Published: 28 August 2017 by MDPI in Molecules

doi: 10.3390/molecules22091423

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake.

0 Reads | 1 Citations
2017
Aug
03
Published new article




Article

Argininosecologanin, a secoiridoid-derived guanidine alkaloid from the roots of Lonicera insularis

Published: 03 August 2017 by Informa UK Limited in Natural Product Research

doi: 10.1080/14786419.2017.1361953

A new secoiridoid-derived guanidine alkaloid, argininosecologanin (1), along with 12 known iridoids and secoiridoids (2–13), was isolated from the roots of Lonicera insularis. The structures of the isolated compounds were established by the spectroscopic analysis and comparison of their spectral data with previously reported data. Compound 1 was assigned as the first secoiridoid-derived guanidine alkaloid isolated as a natural product. A plausible biogenetic pathway for 1 is suggested based on its structural similarity to (E)-aldosecologanin (4).

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2017
Jul
01
Published new article




Article

Cytotoxic pterosins from Pteris multifida roots against HCT116 human colon cancer cells

Published: 01 July 2017 by Elsevier BV in Bioorganic & Medicinal Chemistry Letters

doi: 10.1016/j.bmcl.2017.05.034

Two new pterosin glycosides, (2S,3S)-pterosin C 3-O-β-d-(4'-(E)-caffeoyl)-glucopyranoside (1) and (2S,3S)-pterosin C 3-O-β-d-(6'-(E)-p-coumaroyl)-glucopyranoside (2), were isolated from Pteris multifida (Pteridaceae) roots along with ten known pterosin compounds (3-12). The chemical structures of the isolated compounds were elucidated by extensive analysis of the 1D, 2D NMR, HRESIMS, and CD spectroscopic data. The cytotoxicities of 1-12 against HCT116 human colorectal cancer cell line were evaluated. Among the isolates, compound 1 showed moderate antiproliferative activity in HCT116 cells with an IC50 value of 8.0±1.7μM. Additionally, 1 induced the upregulation of the caspase-9 and procaspase-9 levels in Western blots and increased the annexin V/propidium iodide (PI)-positive cell population in flow cytometry.

0 Reads | 1 Citations
2017
Jul
01
Published new article




Article

TERMINALIA CHEBULA EXTRACT PREVENTS AGAINST SCOPOLAMINE-INDUCED AMNESIA VIA CHOLINERGIC MODULATION AND ANTI-OXIDATIVE EF...

Published: 01 July 2017 by Elsevier BV in Alzheimer's & Dementia

doi: 10.1016/j.jalz.2017.06.157

1 Reads | 0 Citations
2017
May
24
Published new article




Article

Chemical constituents from a Gynostemma laxum and their antioxidant and neuroprotective activities

Published: 24 May 2017 by Springer Nature in Chinese Medicine

doi: 10.1186/s13020-017-0136-y

A few bioactivities of constituents from Gynostemma laxum, which has been collected in Vietnam, have been reported until now. There is no report about the effects of constituents from G. laxum although the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) antioxidant defense system is involved in neuroprotection in the brain. Therefore, we investigated whether quercetin (2), benzoic acid (10) and their analogues (1, 3–9 and 11) from G. laxum have the antioxidant and neuroprotective activities and also their underlying mechanism. To examine their neuroprotective and antioxidant activities, oxytosis, total oxidant scavenging capacity (TOSC), 2,7-dichlorofluorescein (DCFDA), dihydroethidium (DHE), antioxidant response element (ARE)-luciferase reporter gene assays, Western blot analysis, real time-PCR, immunocytochemistry and in silico 3D molecular docking simulation were performed. The study of constituents using chromatographic techniques and spectroscopic analysis showed that G. laxum contained an abundance of quercetin (2), benzoic acid (10) and their analogues (1, 3–9 and 11). Our data demonstrated that quercetin (2) and its analogue (4) among the constituents from G. laxum showed the strongest neuroprotective effect against oxytosis triggered by the excessive amount of glutamate. Compounds 2, 4, 6 and 11 exhibited reactive oxygen species (ROS) inhibitory and ARE transcriptional activities in immortalized hippocampal HT22 cell line. Among them, compound 4, a second active compound, induced Nrf2/HO-1 activation. They were also fit stable onto the Tramtrack and Bric-à-Brac (BTB) domain of Kelch-like ECH-associated protein 1 (Keap1), a known Nrf2 inhibitor protein, based on the results of docking and interaction energies. Overall, these data suggest that –OH and –OCH3 groups of quercetin and its analogues are responsible for their neuroprotective effect. In summary, the major constituents of G. laxum had strong antioxidant and neuroprotective activities so that they could consider as a natural antioxidant supplement. Furthermore, G. laxum might be used beneficially in reducing oxidative complications with the further deep investigation in vivo. The online version of this article (doi:10.1186/s13020-017-0136-y) contains supplementary material, which is available to authorized users.

0 Reads | 3 Citations
2017
May
01
Published new article




Article

Hydrolyzable tannins from the fruits of Terminalia chebula Retz and their α-glucosidase inhibitory activities

Published: 01 May 2017 by Elsevier BV in Phytochemistry

doi: 10.1016/j.phytochem.2017.02.006

Nine hydrolyzable tannins, including three previously unknown and six artifacts, were isolated, together with thirty-nine known ones, from the fruits of Terminalia chebula Retz. (Combretaceae). They were identified as 1,2,3-tri-O-galloyl-6-O-cinnamoyl-β-d-glucose, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose, 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid, 1'-O-methyl neochebulanin, dimethyl neochebulinate, 6'-O-methyl neochebulagate, dimethyl neochebulagate, dimethyl 4'-epi-neochebulagate, and methyl chebulagate by the spectroscopic interpretation. After evaluation for α-glucosidase inhibition of all isolated compounds, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose and 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid showed significant inhibitory activities with IC50 values of 2.9 and 6.4 μM, respectively. In addition, inhibition kinetic studies showed that both compounds have mixed-type inhibitory activities with the inhibition constants (Ki) of 1.9 and 4.0 μM, respectively.

0 Reads | 2 Citations
2017
Apr
25
Published new article




Article

Fast and Simple Discriminative Analysis of Anthocyanins-Containing Berries Using LC/MS Spectral Data

Published: 25 April 2017 by Wiley in Phytochemical Analysis

doi: 10.1002/pca.2689

Introduction Anthocyanins are potent antioxidant agents that protect against many degenerative diseases; however, they are unstable because they are vulnerable to external stimuli including temperature, pH and light. This vulnerability hinders the quality control of anthocyanin‐containing berries using classical high‐performance liquid chromatography (HPLC) analytical methodologies based on UV or MS chromatograms. Objective To develop an alternative approach for the quality assessment and discrimination of anthocyanin‐containing berries, we used MS spectral data acquired in a short analytical time rather than UV or MS chromatograms. Method Mixtures of anthocyanins were separated from other components in a short gradient time (5 min) due to their higher polarity, and the representative MS spectrum was acquired from the MS chromatogram corresponding to the mixture of anthocyanins. Results The chemometric data from the representative MS spectra contained reliable information for the identification and relative quantification of anthocyanins in berries with good precision and accuracy. Conclusion This fast and simple methodology, which consists of a simple sample preparation method and short gradient analysis, could be applied to reliably discriminate the species and geographical origins of different anthocyanin‐containing berries. These features make the technique useful for the food industry. Copyright © 2017 John Wiley & Sons, Ltd.

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2017
Mar
08
Published new article




Article

Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through...

Published: 08 March 2017 by Hindawi Limited in Mediators of Inflammation

doi: 10.1155/2017/5906189

Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (Aβ)42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1β, prostaglandin (PG)E2, and nitric oxide (NO) because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

0 Reads | 4 Citations
2017
Mar
03
Published new article




Article

Catechin-Bound Ceanothane-Type Triterpenoid Derivatives from the Roots of Zizyphus jujuba

Published: 03 March 2017 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.6b01103

Three unprecedented ceanothane-type triterpenoids, ent-epicatechinoceanothic acid A (1), ent-epicatechinoceanothic acid B (2), and epicatechino-3-deoxyceanothetric acid A (3), containing C–C bond linkages with catechin moieties, were isolated from the roots of Zizyphus jujuba. Their chemical structures, including absolute configurations, were established by spectroscopic analysis and calculation of their ECD spectra. A possible biogenetic pathway for C–C bond formation between the catechin and the triterpenoid moieties is presented. Compound 1 was evaluated for its antiproliferative activity on HSC-T6 hepatic stellate cells.

0 Reads | 3 Citations
2017
Feb
02
Published new article




Article

Structure elucidation of a new triterpene from Rhus trichocarpa roots

Published: 02 February 2017 by Wiley in Magnetic Resonance in Chemistry

doi: 10.1002/mrc.4574

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2017
Feb
02
Published new article




Article

Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

Published: 02 February 2017 by MDPI in Molecules

doi: 10.3390/molecules22020224

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship) study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation) of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship) models were developed, using PLS (partial least squares regression) and MLR (multiple linear regression). On the one hand, these models allow for the indication of the most important descriptors (molecular properties) responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study.

0 Reads | 3 Citations
2017
Jan
01
Published new article






New polyhydroxytriterpenoid derivatives from fruits of Terminalia chebula Retz. and their α-glucosidase and α-amylase in...

Published: 01 January 2017 by Elsevier BV in Bioorganic & Medicinal Chemistry Letters

doi: 10.1016/j.bmcl.2016.11.039

Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O-β-d-glycopyranosyl ester (1), 23-O-4′-epi-neochebuloylarjungenin (2), and 23-O-galloylpinfaenoic acid 28-O-β-d-glucopyranosyl ester (17) were isolated from the fruits of Terminalia chebula Retz. along with fourteen known ones. Their structures were elucidated by 1D and 2D NMR spectroscopic data and acid hydrolysis. After evaluating for Baker’s yeast α-glucosidase, rat intestinal α-glucosidase, and porcine pancreatic α-amylase inhibitory activities of all the isolated compounds, 23-O-galloylarjunolic acid (11, IC50 21.7 μM) and 23-O-galloylarjunolic acid 28-O-β-d-glucopyranosyl ester (12, IC50 64.2 μM) showed potent inhibitory activities against Baker’s yeast α-glucosidase compared to the positive control, acarbose (IC50 174.0 μM). However, all the tested compounds except for the positive control, acarbose, had no or only weak inhibitory activity against rat intestinal α-glucosidase and porcine pancreatic α-amylase.

0 Reads | 2 Citations
2017
Jan
01
Published new article




Article

Triterpenoids Isolated from Alnus japonica Inhibited LPS-Induced Inflammatory Mediators in HT-29 Cells and RAW264.7 Cell...

Published: 01 January 2017 by Pharmaceutical Society of Japan in Biological & Pharmaceutical Bulletin

doi: 10.1248/bpb.b16-00895

Alnus japonica (Betulaceae) is a broad-leaved tree easily found in damp regions within the mountains of Korea and Japan. Four triterpenoids (1–4) from the fruits of A. japonica, including the newly isolated 3β-hydroxy-lanost-9(11),23(24)-dien-25,26-diol (3), inhibited the lipopolysaccharide (LPS)-induced expression of the chemotactic cytokine interleukin (IL)-8 and nitric oxide (NO) production in HT-29 colon epithelial cells and RAW264.7 macrophages, respectively. Among these triterpenoids, compound 4, which showed the most potent inhibitory activity, effectively down-regulated LPS-induced protein expression of inducible nitric oxide synthase (iNOS) in RAW264.7 cells and in HT-29 cells. Also, compound 4 concentration-dependently inhibited the levels of LPS-induced pro-inflammatory cytokines, IL-1β and IL-6 in macrophage cells. These triterpenoids isolated from A. japonica fruits are thought to contribute to the anti-inflammatory activities of macrophage and colon epithelial cells, which are important for regulating the colon immune system. They are expected to be potential candidates for therapeutic agents against inflammatory bowel disease.

0 Reads | 2 Citations
2016
Dec
26
Published new article




Article

Anti-Neuroinflammatory ent-Kaurane Diterpenoids from Pteris multifida Roots

Published: 26 December 2016 by MDPI in Molecules

doi: 10.3390/molecules22010027

Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer’s disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract of Pteris multifida (Pteridaceae) roots was found to exhibit significant NO inhibitory activity in lipopolysaccharide (LPS)-activated BV-2 microglia cells. Three new ent-kaurane diterpenoids, pterokaurane M1 2-O-β-d-glucopyranoside (4), 2β,16α-dihydroxy-ent-kaurane 2,16-di-O-β-d-glucopyranoside (10), and 2β,16α,17-trihydroxy-ent-kaurane 2-O-β-d-glucopyranoside (12), were isolated along with nine other known compounds from P. multifida roots. The chemical structures of the new compounds were determined by 1D- and 2D-NMR, HR-ESI-MS, and CD spectroscopic data analysis. Among the isolates, compounds 1 and 7 significantly inhibited NO production in LPS-stimulated BV-2 cells reducing the expression of the cyclooxygenase-2 (COX-2) protein and the level of pro-inflammatory mediators such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. These results suggest that ent-kaurane diterpenes from P. multifida could be potential lead compounds that act as anti-neuroinflammatory agents.

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2016
Dec
01
Published new article




Article

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal ...

Published: 01 December 2016 by Elsevier BV in Journal of Ethnopharmacology

doi: 10.1016/j.jep.2016.08.039

Panax ginseng is one of the most well-known medicinal herbs in Korea and China, which has been used for treatment and prevention of cancer, obesity, diabetes, and cardiovascular diseases. Ginsenosides are the major components of P. ginseng, having a wide range of pharmacological activities. Among the ginsenosides, protopanaxadiol (PPD)-types reportedly have potent anti-cancer effects. Rh2 is PPD-type ginsenoside, and two stereoisomeric forms of Rh2 as 20(S)- and 20(R)-Rh2 were selectively isolated recently. The biological activities of Rh2 ginsenosides are known to depend on their differences in stereochemistry. Colorectal cancer (CRC) is one of the most lethal neoplasm, and cancer-related death is usually associated with metastasis to other organs. We aimed this study to investigate whether 20(S)- and 20(R)-Rh2 can suppress tumor invasion in human CRC cells. 20(S)- and 20(R)-Rh2 were isolated from the roots of ginseng. Human CRC cells were incubated with 20(S)- or 20(R)-Rh2 in the presence or absence of interleukin-6. An MTT assay was used to measure cell viability. Western blot and quantitative real-time PCR analyses were performed to determine levels of expression and phosphorylation. An invasion assay was performed using a Boyden chamber system with the Matrigel-coated membrane to measure cancer cell invasion. 20(S)- and 20(R)-Rh2 showed differential cytotoxic activity. Only 20(S)-Rh2 decreased cancer cell viability. Additionally, 20(S)-Rh2 effectively inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of matrix metalloproteinases (MMPs), including MMP-1, −2, and −9, resulting in inhibition of cancer cell invasion. Interestingly, these pharmacological activities of 20(S)-Rh2 were more potent than those of 20(R)-Rh2. Furthermore, combination treatment showed that 20(S)-Rh2 enhanced the sensitization of doxorubicin-treated anti-cancer activities in CRC cells. Our results demonstrated that ginsenoside 20(S)-Rh2 has therapeutic potential for the treatment with CRC and may be valuable as a combination partner with more classic chemotherapeutic agents, such as doxorubicin, to treat CRC.

0 Reads | 6 Citations
2016
Dec
01
Published new article




Article

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardi...

Published: 01 December 2016 by Wiley in Phytochemical Analysis

doi: 10.1002/pca.2659

Introduction DA‐9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA‐9801, considering its high contents of both primary and secondary metabolites. Objective Development of a quality assessment strategy for DA‐9801, based on the combination of UHPLC‐QTOF/MS, HPLC‐ELSD, and 1H–NMR spectroscopy. Methods The method was developed and tested with 15 batch products of DA‐9801. The steroidal saponins of DA‐9801 were tentatively identified by UHPLC–QTOF/MS and were quantified with the validated HPLC–ELSD method. Primary metabolites of DA‐9801 were identified and profiled using 1H–NMR spectrometry. The batch‐to‐batch equivalence of DA‐9801 was tested with the 1H–NMR spectra using spectral binning, correlation analysis, and principal component analysis. Results Six major saponins of DA‐9801 were tentatively identified by UHPLC‐QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC‐ELSD method. Twenty‐six metabolites were identified in 1H–NMR spectra. The similarity between DA‐9801 batches could be evaluated with the NMR spectra of DA‐9801. The 1H–NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA‐9801. Conclusion This study validates the effectiveness of UHPLC‐QTOF/MS, HPLC‐ELSD, and 1H NMR‐combined method for quality control of DA‐9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd.

0 Reads | 2 Citations
2016
Nov
22
Published new article




Article

Platyphylloside Isolated From Betula platyphylla Inhibit Adipocyte Differentiation and Induce Lipolysis Via Regulating A...

Published: 22 November 2016 by Medknow in Pharmacognosy Magazine

doi: 10.4103/0973-1296.192208

Obesity causes or aggravates many health problems, both independently and in association with several pathological disorders, including Type II diabetes, hypertension, atherosclerosis, and cancer. Therefore, we screened small compounds isolated from natural products for the development of anti-obesity drugs. The purpose of this study was to investigate the anti-adipogenic activities of platyphylloside, diarylheptanoid isolated from Betula platyphylla, which was selected based on the screening using 3T3-L1 cells. To evaluate the inhibition of adipocyte differentiation and lipolysis, lipid contents of BPP on were measured using Oil Red O staining in 3T3-L1 cells. The mRNA and protein expression levels of various adipokines were measured by Quantitative real-time PCR and Western blotting analysis, respectively. Platyphylloside showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 cells and suppressed adipocyte differentiation even in the presence of troglitazone, a PPARγ agonist. Platyphylloside might suppress adipocyte differentiation through PPARγ, C/EBPα, and SREBP1-induced adipogenesis, which is synergistically associated with downstream adipocyte-specific gene promoters such as aP2, FAS, SCD-1, LPL, and Adiponectin. In addition, platyphylloside affected lipolysis by down-regulating perilipin and HSL and up-regulating TNFα. Taken together, the results reveal that platyphylloside has anti-adipogenic activity and highlight its potential in the prevention and treatment of obesity. The extract of B. platyphylla bark and its isolate, BPP, had anti-adipogenic activity in 3T3-L1 cells via suppression of adipocyte differentiation from preadipocytes.Treatment with BPP significantly down-regulated the expression of PPARγ, C/EBP, C/EBPβ, C/EBPδ, SREBP1c, SCD-1, FAS, aP2 and LPL.BPP induced a lipolytic response in mature adipocytes via up-regulation krof TNFá and down-regulation of HSL, perilipin, PPARγ, PDE3B, and Gia1.BPP is a novel potential agent in the prevention and treatment of obesity through its anti-adipogenic activities and lipolysis. Abbreviations used: DMEM: Dulbecco's modified Eagle's medium, FBS: fetal bovine serum, ORO: Oil Red O, PBS: phosphate buffered saline, RT: room temperature, PPAR: peroxisome proliferator-activated receptor, C/EBP: CCAAT/enhancer-binding protein, SREBP1: sterol regulatory element binding protein 1, SCD-1: steroyl-coenzyme A desaturase 1, LPL: lipoprotein lipase, aP2: adipocyte fatty acid binding protein, FAS: fatty acid synthase, HSL: hormone sensitive lipase, Giα1: GPT binding protein, PDE3B: phosphodiesterase 3B, TNFα: tumor necrosis factor α, GAPDH: glyceraldehyde 3-phosphate dehydrogenase, SD: standard deviation, EGCG: epigallocatechin-3-gallate, TZD: thiazolidinediones.

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2016
Nov
01
Published new article




Article

Involvement of heme oxygenase-1 induction in the cytoprotective and neuroinflammatory activities of Siegesbeckia Pubesce...

Published: 01 November 2016 by Elsevier BV in International Immunopharmacology

doi: 10.1016/j.intimp.2016.08.030

Glutamate-induced oxidative injury contributes to neuronal degeneration such as Alzheimer's disease, Parkinson's disease and Huntington's disease in the central nervous system (CNS). Siegesbeckia pubescens is used in oriental medicine to treat arthritis, stroke, rash, edema, and skin itching eczema in South-East Asia. This study provides evidence that 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (DTMF), a compound isolated from 90% MeOH extract of Siegesbeckia pubescens, effectively has neuroprotective and anti-neuroinflammatory activities. DTMF has cytoprotective and reactive oxygen species (ROS) reductive effects in HT22 cells. DTMF also decreased LPS-induced inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) expression but attenuated LPS-induced nitrite (NO) and prostaglandin E2 (PGE2), as well as TNF-α and IL-1β production. In addition, DTMF induced Heme oxygenase (HO)-1 expression, HO activity, nuclear transcription factor erythroid-2 related factor 2 (Nrf2) nuclear translocation, and antioxidant response element (ARE)-luciferase activity. DTMF increased p38 phosphorylation in HT22 cells and JNK phosphorylation in BV2 microglia cells. Thus, p38 inhibitor (SB203580) in HT22 cells and JNK inhibitor (SP600125) in BV2 microglia cells significantly suppressed HO-1 expression by DTMF. Furthermore, treatment with SnPP (an inhibitor of HO activity) significantly blocked the cytoprotective effects and the anti-neuroinflammatory action of DTMF. In addition, activated microglia-mediated cell death of mouse hippocampal HT22 cells was significantly repressed by DTMF. We also investigated the protective effect of DTMF on the death of glutamate-induced primary mouse hippocampal neurons. These results demonstrated that DTMF may be a good therapeutic agent against neurodegenerative diseases induced by oxidative stress.

0 Reads | 1 Citations
2016
Sep
22
Published new article




Article

Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidativ...

Published: 22 September 2016 by Informa UK Limited in Bioscience, Biotechnology, and Biochemistry

doi: 10.1080/09168451.2016.1234930

Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

0 Reads | 1 Citations
2016
Sep
12
Published new article




Article

Cytotoxic Ceanothane- and Lupane-Type Triterpenoids from the Roots of Ziziphus jujuba

Published: 12 September 2016 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.6b00525

Ziziphus jujuba, a plant in the family Rhamnaceae, is used in several Asian countries as a food and traditional medicine. Fifteen new ceanothane-type (1–15) and three new lupane-type triterpenoids (16–18) were isolated from the roots of Z. jujuba, as well as 12 previously known triterpenoids (19–30). Their structures were elucidated by 1D and 2D NMR spectroscopic and HR mass spectrometric data analysis. Compounds 12 and 13 were found to possess a rare E-ring γ-lactone structure, and 14 was assigned as the first 2,28-dinorlupane derivative isolated as a natural product. Twenty-five of the isolates were examined for cytotoxicity against human hepatocellular carcinoma HepG2 cells, and compounds 6–8, 14, 17, 23, 25, 29, and 30 showed cytotoxicity with IC50 values ranging from 1.9 to 5.9 μM.

0 Reads | 3 Citations
2016
Sep
02
Published new article




Article

Acylphloroglucinolated Catechin and Phenylethyl Isocoumarin Derivatives from Agrimonia pilosa

Published: 02 September 2016 by American Chemical Society (ACS) in Journal of Natural Products

doi: 10.1021/acs.jnatprod.6b00566

Eight new compounds (1–8), including five acylphloroglucinolated catechins (1–5) and three phenylethyl isocoumarin glycosides (6–8), were isolated from Agrimonia pilosa along with six other known compounds (9–14). The new compounds were characterized structurally by NMR, MS, and ECD analyses. Compounds 4 and 5 were assigned as acylphloroglucinolated procyanidin derivatives, which are described for the first time from Nature. The absolute configuration of compound 8 was elucidated by computational analysis of its ECD spectrum. The isolated compounds were evaluated for their inhibitory activity against lipopolysaccharide-induced NO production in BV2 microglial cells.

0 Reads | 1 Citations
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