Showing papers in "Natural product sciences in 2015"

Pestalotiolide A, a New Antiviral Phthalide Derivative from a Soft Coral-derived Fungus Pestalotiopsis sp.

Abstract: − Chemical investigation of the fermentation broth of a Soft Coral-Derived fungus Pestalotiopsis sp., led to the isolation of a new phthalide derivative, pestalotiolide A (1), three known analogues (2, 3 and 4), along with 5'-O-acetyl uridine (5) first isolated as a natural product. The structure of the new compound (1) was established by comprehensive spectroscopic analysis and chemical methods. Compounds 1 4 possessed varying degrees of antiviral activities, which was reported for the first time. Compared to the positive control ribavirin (IC50 = 418.0 μM), pestalotiolide A (1) exhibited significant anti-EV71 activity in vitro, with an IC50 value of 27.7 μM. Furthermore, the preliminary structure-activity relationship of antiviral activities was also discussed.

Viriditoxin Induces G2/M Cell Cycle Arrest and Apoptosis in A549 Human Lung Cancer Cells

Abstract: Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTPbinding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to β-tubulin indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.

Viridicatol from Marine-derived Fungal Strain Penicillium sp. SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-kappaB Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells

Abstract: Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B (NF-κB) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B (IκB)- α in the cytoplasm, and suppressed the translocation of NF-κB p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of NF-κB in LPS-stimulated RAW264.7 and BV2 cells.

The Extract of Limonium tetragonum Protected Liver against Acute Alcohol Toxicity by Enhancing Ethanol Metabolism and Antioxidant Enzyme Activities

Abstract: 【The protective effect of EtOAc fraction of Limonium tetragonum extract (EALT) against alcohol-induced hepatotoxicity was assessed following acute ethanol intoxication in Spraque-Dawley rats. EALT (200 mg/kg p.o.) was administrated once before alcohol intake (8 g/kg, p.o.). Blood ethanol concentration, and the activities of alcohol metabolic enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were measured. Also, the formation of malondialdehyde (MDA) and the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase were determined after acute alcohol exposure. Pretreatment of rats received ethanol with EALT significantly decreased blood ethanol concentration and elevated the activities of ADH and ALDH in liver. The increased MDA level was decreased, and the reduced activities of SOD, GSH-px and catalase were markedly preserved by the treatment with EALT. This study suggests that EALT prevent hepatic injury induced by acute alcohol which is likely related to its modulation on the alcohol metabolism and antioxidant enzymes activities.】

Anti-inflammatory Activity of Fucoidan with Blocking NF-kappaB and STAT1 in Human Keratinocytes Cells

Abstract: Fucoidan, a sulfated polysaccharide is found in several types of edible brown algae. It has shown numerous biological activities; however, the molecular mechanisms on the activity against atopic dermatitis have not been reported yet. We now examined the effects of fucoidan on chemokine production co-induced by TNF-α/ IFN-γ, and the possible mechanisms underlying these biological effects. Our data showed that fucoidan inhibited the TNF-α/IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC) mRNA in human keratinocytes HaCaT cells. Also, fucoidan suppressed phosphorylation of nuclear factor kappa B (NF-κB) and activation of signal transducer and activator of transcription (STAT)1 in a dose-dependent manner. In addition, fucoidan significantly inhibited activation of extracellular-signal-regulated kinases (ERK) phosphorylation. These data indicate that fucoidan shows anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-induced chemokines by blocking NF-κB, STAT1, and ERK1/2 activation, suggestive of as used as a therapeutic application in inflammatory skin diseases, such as atopic dermatitis.

Isolation and Development of Quantification Method for Cyanidin-3-Glucoside and Cyanidin-3-Rutinoside in Mulberry Fruit by High-Performance Countercurrent Chromatography and High-Performance Liquid Chromatography

Abstract: 【Cyanidin-3-glucoside (C3G) and cyanidin-3-rutinoside (C3R) were isolated by high-performance countercurrent chromatography (HPCCC) using a two-phase solvent system composed of tert-butyl methyl ether/n-butanol/acetonitrile/water/trifluoroacetic acid (1 : 3 : 1 : 5 : 0.01, v/v) to give pure C3G (34.1 mg) and C3R (14.3 mg) from 1.5 g crude mulberry fruit extract. Using the pure C3G and C3R, a reliable high-performance liquid chromatography (HPLC) method was developed and validated to determine the C3G and C3R contents in mulberry fruit. C3G and C3R were separated simultaneously using an Eclipse XDB-C18 column ( $4.6{\times}250mm$ I.D., $5{\mu}m$ ) coupled with a photodiode array detector (PDA). The gradient elution of the mobile phase consisting of acetonitrile (0.5% formic acid) and water (0.5% formic acid) was applied (1.0 mL/min), and the detection wavelength was 520 nm. The calibration curves of C3G and C3R showed good linearity (both with $r^2=0.9996$ ) in the concentration range $15.625-500{\mu}g/mL$ , and the relative standard deviations (RSD%) of intra- and inter-day variability were in the ranges 2.1 - 8.2% and 4.1 - 17.1%, respectively. The accuracies were ranged 96.5 - 102.6% for C3G and C3R, respectively. The developed HPLC method was used to determine the contents of C3G and C3R in newly harvested mulberry from eight different provinces of Korea.】

Quantitative Analysis of the Flavonoid Content in the Leaves of Boehmeria nivea and Related Commercial Products

Abstract: 【Content analysis of flavonoids (epicatechin, epicatechin gallate, and rutin) present in the leaves of Boehmeria nivea (originating from Geumsan-myeon, Biin-myeon, Hansan-myeon, and Baeksu-eup) and their commercial products (ramie tteok, ramie songpyeon, ramie bory-tteok, and ramie tea) was conducted by HPLC. The content of epicatechin, epicatechin gallate, and rutin was highest in the leaves of B. nivea from Geumsan-myeon (0.138 mg/g), Baeksu-eup (1.654 mg/g) and Geumsan-myeon (12.205 mg/g), respectively. With respect to commercial products, the content of epicatechin and epicatechin gallate was highest in ramie tea, with concentrations of 1.879 and 1.090 mg/g, respectively. Given these flavonoid concentrations, B. nivea leaf extracts have the potential to be used as additives in natural medicinal products, health supplements, and beverages.】

Chemical Constituents from the Aerial Parts of Bupleurum falcatum L. and Biological Evidences

Abstract: − In this study, phytochemical investigation on the aerial parts of Bupleurum falcatum resulted in the isolation of fourteen compounds including three quinic acid derivatives (1 3), five flavonoids (4 8), three monoterpene glycosides (9 11), and three saikosaponins (12 14). Compound 1 was first isolated from nature and unambiguously determined to be 3-O-feruloyl 5-O-caffeoylquinic acid on the basis of the extensive spectroscopic evidence. Biological testing revealed that saikosaponin A (12) and saikosaponin D (13) showed moderate antiproliferative effects on HL-60 and HepG2 cancer cell lines.

Identification of Dammarane-type Triterpenoid Saponins from the Root of Panax ginseng

Abstract: 【The root of Panax ginseng, is a Korea traditional medicine, which is used in both raw and processed forms due to their different pharmacological activities. As part of a continued chemical investigation of ginseng, the focus of this research is on the isolation and identification of compounds from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, semi-preparative-high performance liquid chromatography, Fast atom bombardment mass spectrometric, and nuclear magnetic resonance. Dammarane-type triterpenoid saponins were isolated from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, and semi-preparative-high performance liquid chromatography. Their structures were identified as protopanaxadiol ginsenosides [gypenoside-V ( 1 ), ginsenosides-Rb1 ( 2 ), -Rb2 ( 3 ), -Rb3 ( 4 ), -Rc ( 5 ), and -Rd ( 6 )], protopanaxatriol ginsenosides [20(S)-notoginsenoside-R2 ( 7 ), notoginsenoside-Rt ( 8 ), 20(S)-O-glucoginsenoside-Rf ( 9 ), 6-O-[ $\alpha$ -L-rhamnopyranosyl(1 $\rightarrow$ 2- $\beta$ -D-glucopyranosyl]-20-O- $\beta$ -D-glucopyranosyl- $3\beta$ , $12\beta$ , 20(S)-dihydroxy-dammar-25-en-24-one ( 10 ), majoroside-F6 ( 11 ), pseudoginsenoside-Rt3 ( 12 ), ginsenosides-Re ( 13 ), -Re5 ( 14 ), -Rf ( 15 ), -Rg1 ( 16 ), -Rg2 ( 17 ), and -Rh1 ( 18 ), and vinaginsenoside-R15 ( 19 )], and oleanene ginsenosides [calenduloside-B ( 20 ) and ginsenoside-Ro ( 21 )] through the interpretation of spectroscopic analysis. The configuration of the sugar linkages in each saponin was established on the basic of chemical and spectroscopic data. Among them, compounds 1 , 8 , 10 , 11 , 12 , 19 , and 20 were isolated for the first time from P. ginseng root.】

Phenolic Constituents from the Flowers of Hamamelis japonica Sieb. et Zucc.

Abstract: − Hamamelis japonica (Hamamelidaceae), widely known as Japanese witch hazel, is a deciduous flowering shrub that produces compact clumps of yellow or orange-red flowers with long and thin petals. As a part of our ongoing search for phenolic constituents from this plant, eleven phenolic constituents including six flavonol glycosides, a chalcone glycoside, two coumaroyl flavonol glycosides and two galloylated compounds were isolated from the flowers. Their structures were elucidated as methyl gallate (1), myricitrin (2), hyperoside (3), isoquercitrin (4), quercitrin (5), spiraeoside (6), kaempferol 4'-O-β-glucopyranoside (7), chalcononaringenin 2'-O-β-glucopyranoside (8), trans-tiliroside (9), cis-tiliroside (10), and pentagalloyl-O-β-D-glucose (11), respectively. These structures of the compounds were identified on the basis of spectroscopic studies including the on-line LCNMR-MS and conventional NMR techniques. Particularly, directly coupled LC-NMR-MS afforded sufficient structural information rapidly to identify three flavonol glycosides (2 4) with the same molecular weight in an extract of Hamamelis japonica flowers without laborious fractionation and purification step. Cytotoxic effects of all the isolated phenolic compounds were evaluated on HCT116 human colon cancer cells, and pentagalloyl-O-βD-glucose (11) was found to be significantly potent in inhibiting cancer cell growth.

Anti-inflammatory Activities of Lupane-triterpenoids In Vitro and Their Phytochemical Fingerprinting from Leaves of Acanthopanax gracilistylus

Abstract: 【The activities on the inhibition of NO on LPS-induced RAW 264.7 macrophages were investigated in this work. A simple and sensitive method has been developed and validated for fingerprinting analysis of leaves of Acanthopanax gracilistylus W.W. Smith (AGS). The cytotoxicity and inhibition of NO on LPS-induced RAW 264.7 cells of the extract and triterpenoids were determined. Optimal conditions of HPLC analysis were established as follows. The separation was performed with an ODS-C 18 column at $30^{\circ}C$ , the detected wavelength was 210 nm, the flow rate was 1 mL/min, and the mobile phase consisted of acetonitrile (0.05% phosphoric acid)-0.05% phosphoric acid solution with gradient elution. Our results showed that impressic acid and acankoreaogenin was more effective on the inhibition of NO than the methanol extract and other compounds. There were seventeen peaks coexisted with similarities above 0.95 and nine lupane-triterpenoids including acankoreaogenin and impressic acid detected and identified. The result of anti-inflammatory activities provides a potential explanation for the use of AGS leaves as a herbal medicine in the treatment of inflammatory diseases. Our results also show that acankoreanogenin and impressic acid may be potentially useful in developing new anti-inflammatory agents. In addition, the fingerprint chromatography clearly illustrated and confirmed the material basis for the anti-inflammatory activities of this plant.】

Chemical Constituents from Leaves of Acanthopanax henryi (II)

Abstract: Nineteen compounds, including one organic acid (1), one anthraquinone (2), one amide (3), and sixteen triterpenoid saponins (4 - 19) were isolated from the leaves of Acanthopanax henryi (Oliv.) Harms (Araliaceae). Their structures were determined on the basis of physicochemical properties and spectral analyses (HR-MS and NMR). Among them, compounds 2, 3, 7, 12 and 19 were new within Araliaceae. Compounds 4, 5, 9 - 11, 13, 14, 16 and 18 were reported for the first time from the Acanthopanax genus. Except for compounds 4 and 9, other compounds were isolated from A. henryi (Oliv.) Harms for the first time. The rare anthraquinone, compound 2, significantly decreased the production of NO and the levels of other inflammatory factors, such as TNF-α and IL-6, in lipopolysaccharide (LPS)-stimulated macrophages in a dose-dependent manner. This is the first time to report anti-inflammatory effect of this compound.

Violapyrone J, α-Pyrone Derivative from a Marine-derived Actinomycetes, Streptomyces sp.

Abstract: − A new α-pyrone derivative, violapyrone J (1), and along with the two known violapyrones B (2) and C (3) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. SC0718. The structure of violapyrone J (1) was elucidated from 1D and 2D NMR spectroscopic analyses.

Salternamide E from a Saltern-derived Marine Actinomycete Streptomyces sp.

Abstract: − Comprehensive chemical analysis of extracts and fractions of marine actinomycete strains led to the discovery of a new minor secondary metabolite, salternamide E (1), from a saltern-derived halophilic Streptomyces strain. The planar structure of salternamide E (1) was elucidated by a combinational analysis of spectroscopic data including NMR, MS, UV, and IR. The absolute configuration of salternamide E (1) was determined by circular dichroism spectroscopic analysis. Salternamide E displayed weak cytotoxicity against various human carcinoma cell lines.

Anti-inflammatory Effect of Dactyloquinone B and Cyclospongiaquinone-1 Mixture in RAW264.7 Macrophage and ICR Mice

Abstract: Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. TNF-α, IL-1β, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent. Keywords - Dactyloquinone B, Cyclospongiaquinone-1, Anti-inflammatory effect, Ear edema model

Articles : Bioactive Constituents from the Leaves of Zanthoxylum schinifolium

Abstract: − Activity-guided separation of the methylene chloride-soluble fraction of the leaves of Zanthoxylum schinifolium, resulted in the isolation of four coumarinoids (1 − 4), two triterpenoids (5, 6) and three fatty acid derivatives (7 − 9) as active principles. Their chemical structures were identified as collinin (1), 8-methoxyanisocoumarin (2), 7-(6'R-hydroxy-3',7'-dimethylocta-2',7'-dienyloxy)-coumarin (3), (E)-4-methly-6-(coumarin-7'-yloxy) hex-4-enal (4), lupeol (5), epi-lupeol (6), phytol (7), hexadec-3-enoic acid (8) and palmitic acid (9), on the basis of spectroscopic (1D, 2D and MS) data analyses and comparing with the data published in the literatures. Compounds 1 and 7 showed potent cytotoxicity against Jurkat T cells with IC50 values of 45.58 and 47.51 μM, respectively. The others showed moderate activity with IC50 values ranging around 80.58 to 85.83 μM, while the positive control, auraptene, possessed an IC50 value of 55.36 μM.

NF-κB Inhibitory Activities of Phenolic and Lignan Components from the Stems of Acanthopanax divaricatus var. albeofructus

Abstract: − Acanthopanax divaricatus var. albeofructus (ADA) is commonly ingested as a traditional medicine or as a component of a health drink in Korea. In this phytochemical study, nine phenolics (1 9) and three lignans (10 12) were isolated from the MeOH extract of the stems of ADA. Chemical structures were elucidated by comparing spectroscopic data with reported values. Nuclear factor kappa B (NF-κB) inhibitory activity of the isolated compounds was evaluated using an NF-κB luciferase assay in HepG2 cells. Among them, compounds 1, 3 8, and 11 showed significant inhibitory effects on TNFα-induced NF-κB transcriptional activity in a dosedependent manner, with IC50 values ranging from 13.25 to 37.36 μM. Further studies on potential antiinflammatory effects and the benefits of phenolic and lignan components from ADA are warranted.

Two New Scalaranes from a Korean Marine Sponge Spongia sp.

Abstract: Intensive chemical investigation of Korean marine sponge Spongia sp. has led to the isolation of two new scalaranes. The planar structures of the new compounds 1 and 2 were determined through 1D and 2D NMR spectral data analysis, while the relative stereochemistry of the compounds was determined based on the analysis of 1 H- 1 H coupling constants and NOESY spectroscopic data. Compounds 1 and 2 did not display any significant biological activities on farnesoid X-activated receptor (FXR) in co-transfection assay. KeywordsScalarane, Sesterpenoid, Spongia sp., Korean sponge, Marine natural product

Anti-Helicobacter pylori Compounds from Maackia amurensis

Abstract: − Eight isoflavonoid compounds were isolated from the EtOAc fraction of Maackia amurensis which had shown the highest anti-Helicobacter pylori activity among the fractions, using medium pressure liquid chromatography and recrystallization. Based on the spectroscopic data including H-NMR, C-NMR, HMBC and MS data, the chemical structures of the isolates were determined to be (−)-medicarpin (1), afromosin (2), formononetin (3), tectorigenin (4), prunetin (5), wistin (6), tectoridin (7) and ononin (8). Anti-H. pylori activity of each compound was evaluated with broth dilution assay. As a result, (−)-medicarpin (1), tectorigenin (4) and wistin (6) showed anti-H. pylori activity. (−)-Medicarpin (1) exhibited the most potent growth inhibitory activity against H. pylori with the minimal inhibitory concentration (MIC)90 of 25 μM, and tectorigenin (4) with MIC90 of 100 μM ranked the second. This is the first study to show the anti-H. pylori activity of M. amurensis, and it is suggested that the stem bark of M. amurensis or the EtOAc fraction or the isolated compounds can be a new natural source for the treatment of H. pylori infection.

Penidioxolanes A and B, 1,3-Dioxolane Containing Azaphilone Derivatives from Marine-derived Penicillium sp. KCB12C078

Abstract: Two new azaphilone derivatives containing 1,3-dioxolane moiety, penidioxolanes A (1) and B (2), were isolated from marine-derived fungus Penicillium sp. KCB12C078, together with four known compounds (36) by chemical investigation. Compounds 1 6 were isolated by combination of silica gel, ODS column chromatography and preparative HPLC. Their structures were determined by analysis of spectroscopic data including 1D-, 2D-NMR, and MS techniques. The isolates were evaluated against cancer cell growth inhibition effects and antimicrobial activity.

Anti-Inflammatory Effect of Violapyrones B and C from a Marine-derived Streptomyces sp.

Abstract: Recently, we reported violapyrones B, C, H and I, unusual 3, 4, 6-trisubstituted α-pyrone derivatives, from the culture broth of the marine Streptomyces sp. 112CH148. In previous studies, violapyrones have been shown to have antibacterial and antitumor activities. However, the anti-inflammatory effect of violapyrones has not been reported yet. As part of our ongoing study for the discovery of bioactive metabolites from marine microorganisms, we found that violapyrones also have anti-inflammatory activity. In this study, we investigated the effect of violapyrones on LPS-induced inflammatory responses in vitro. Violapyrones B and C did not affect the viability of RAW 264.7 cells at concentrations up to 25 μM. However, violapyrones B and C inhibited the production of NO compared to the LPS-induced control. In addition, violapyrones B and C down-regulated the expression of iNOS protein in LPS-stimulated RAW 264.7 cells. To the best of our knowledge, this is the first report on the anti-inflammatory activity of violapyrones B and C. Keywords − Violapyrones, α-Pyrones, Streptomyces sp., Anti-inflammatory