Showing papers in "Planta Medica in 2004"
TL;DR: This review focuses on the naturally-occurring compounds with anti-inflammatory properties and attempts to correlate their actions with the modulation of cytokines and associated intracellular signalling pathways.
Abstract: It has been widely shown that many plant-derived compounds present significant anti-inflammatory effects. For this reason, they represent potential molecules for the development of new drugs, especially designed for the treatment and/or control of chronic inflammatory states such as rheumatism, asthma, inflammatory bowel diseases, atherosclerosis, etc. This review focuses on the naturally-occurring compounds with anti-inflammatory properties and attempts to correlate their actions with the modulation of cytokines and associated intracellular signalling pathways; it continues the review published in the November, 2003 issue of Planta Medica. Abbreviations. AP-1:activator protein-1 CCR1:chemokine receptor 1 CINC-1:cytokine-induced neutrophil chemoattractant 1 COX:cyclooxygenase EGCG:(-)-epigallocatechin gallate ELAM-1:endothelial-leukocyte adhesion molecule-1 ERK:extracellular signal-regulated kinase GRO:growth-related oncogene HUVEC:human umbilical vein endothelial cells ICAM-1:intercellular adhesion molecule-1 IFN:interferon IL:interleukin iNOS:inducible nitric oxide synthase IRA:the natural interleukin receptor activation JAK:janus kinase JNK:c-Jun NH2-terminal kinase LPS:lipopolysaccharide MAPK:mitogen-activated protein kinases MCP:monocyte chemotactic protein MHC:major histocompatibility complex MIP:macrophage inflammatory protein MMP:matrix metalloproteinases MPO:myeloperoxidase NF-kappaBnuclear factor kappa B NO:nitric oxide PAF:platelet aggregation factor PGEE:prostaglandin PK:protein kinase PMA/TPA:phorbol myristate acetate RANTES:regulated upon activation normal T-cell expressed and secreted TGF-beta:transforming growth factor-beta TNFalpha:tumour necrosis factor VCAM-1:vascular cell adhesion molecule-1
413 citations
TL;DR: Evidence is presented to show that some mammalian metabolites of PPT may indeed be able to protect the vascular endothelium and that diets rich in P PT may in humans at normal dietary levels have the ability to protect against Type II diabetes and the metabolic syndrome through effects on glucose absorption and associated hormones.
Abstract: This paper seeks to catalyse a reappraisal of the nature, fate and biological significance in humans of phenols, polyphenols and tannins (PPT) consumed in normal diets, and in particular questions the primacy of PPT radical-scavenging mechanisms for the supposed health benefits of diets rich in fruits and vegetables. PPT are classified by structure and function. Arguments are presented to show that cinnamates and derived polyphenols make significantly larger contributions to the total PPT intake than the flavonols and flavones upon which the vast majority of attention has been focussed previously. Daily intakes of total PPT may range from less than 100 mg to in excess of 2 g, and the critical importance of coffee and black tea as the major dietary sources is shown. Only some 5% of the dietary PPT is absorbed in the duodenum, and of this only some 5%, mainly flavanols, reaches the plasma unchanged, the balance being mammalian conjugates. Over 95% of the intake passes to the colon and is fermented by the gut microflora. A fraction of the resulting microbial metabolites is absorbed and appears in the plasma primarily as mammalian conjugates. Even following high intakes of PPT, the plasma metabolites collectively make a very small (less than 5%) and transient contribution to the total concentration of redox active substances in plasma. This explains the failure of most studies that sought to detect an increase in plasma antioxidant power after consuming a PPT-rich meal or supplement. The powerfully antioxidant PPT aglycones, much used in in vitro studies, do not reach the plasma. The redox potential of those unchanged PPT and PPT metabolites that reach the plasma enables them to scavenge damaging radicals, but the endogenous plasma antioxidants, especially ascorbate, are required for disposal of the resultant phenoxyl radicals. Black tea and coffee, the major sources of PPT, are poor sources of ascorbate. It is suggested that if diets rich in fruits and vegetables are health-promoting, and if these effects are due to PPT, then alternatives to radical-scavenging mechanisms must be sought. Evidence is presented to show that some mammalian metabolites of PPT may indeed be able to protect the vascular endothelium and that diets rich in PPT may in humans at normal dietary levels have the ability to protect against Type II diabetes and the metabolic syndrome through effects on glucose absorption and associated hormones. Such effects are recommended for further investigation.
384 citations
TL;DR: The data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection and there is also preliminary evidence of a preventative effect.
Abstract: Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.
227 citations
TL;DR: This work reports the first example of diterpenoids as inhibitors of AChE, and indicates that these compounds have potential to penetrate the blood-brain barrier.
Abstract: Acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors are the only registered drugs used to treat Alzheimer's disease (AD). New AChE inhibitors may contribute to the design of new pharmaceuticals and supply information which will facilitate the understanding of the interaction between inhibitors and the enzyme. The dried root of Salvia miltiorhiza is called 'Danshen' in China, and has been used for the treatment of cerebrovascular disease and CNS deterioration in old age for over one thousand years. In this work, a modified Ellman method was used to guide the fractionation of the active AChE inhibitory compounds from an acetone extract. Four inhibitory compounds, dihydrotanshinone, cryptotanshinone, tanshinone I and tanshinone IIA were isolated, and the structures were identified by comparison of their spectral characteristics with previous reports. The inhibitory activities of dihydrotanshinone and cryptotanshinone were dose-dependent, their IC (50) values being 1.0 microM and 7.0 microM, respectively. These two compounds were the major inhibitory compounds in the extract as judged by HPLC analysis, forming 0.054 % w/w and 0.23 % w/w in the dried root, respectively, and in mixture they appear to be less active than as isolated compounds. The clogP values of dihydrotanshinone, cryptotanshinone, tanshinone I and tanshinone IIA were calculated as 2.4, 3.4, 4.8 and 5.8, respectively, which indicate that these compounds have potential to penetrate the blood-brain barrier. This is the first example of diterpenoids as inhibitors of AChE.
163 citations
TL;DR: Alpha-hederin, hederasaponin-C, as well as hederacolchisides-E and -F exhibited a strong total antioxidant activity, and these various antioxidant activities were compared with model antioxidants such as a-tocopherol, butylated hydroxyanisole (BHA) andbutylated hydroxytoluene (BHT).
Abstract: The antioxidant activities of alpha-hederin and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F from Hedera colchica were investigated, in this study. The antioxidant properties of the saponins were evaluated using different antioxidant tests: 1,1-di-phenyl-2-picryl-hydrazyl (DPPH.) free radical scavenging, total antioxidant activity, reducing power, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Alpha-hederin, hederasaponin-C, as well as hederacolchisides-E and -F exhibited a strong total antioxidant activity. At the concentration of 75 pg/mL, these saponins showed 94, 86, 88 and 75% inhibition on lipid peroxidation of linoleic acid emulsion,respectively. These various antioxidant activities were compared with model antioxidants such as a-tocopherol, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT).
160 citations
Ohio State University1, University of Illinois at Chicago2, Ewha Womans University3, University of Minnesota4, Korea Research Institute of Bioscience and Biotechnology5, University of Arizona6, Purdue University7, National Institutes of Health8, University of Texas Health Science Center at Houston9, Northwestern University10, Loyola University Chicago11
TL;DR: Based on this large pool of potential cancer chemopreventive compounds, structure-activity relationships are discussed in terms of the quinone reductase induction ability of flavonoids and withanolides and the cyclooxygenase-1 and -2 inhibitory activities of flavanones, flavones and stilbenoids.
Abstract: For the purpose of finding nontoxic cancer preventive agents, we studied natural products derived from marine and plant sources. The following compounds inhibited tumor promotion on mouse skin in two-stage carcinogenesis experiments: two marine natural products and four plant natural products. Among these natural inhibitors, we suggest green tea as a cancer preventive in humans. This chapter reviews our basic study on cancer preventive agents derived from natural sources.
150 citations
TL;DR: Lycorine-type alkaloids were the most active alkaloid with 1- O-acetyllycorine exhibiting inhibitory effects two-fold more potent than that of galanthamine.
Abstract: Twenty-three Amaryllidaceae alkaloids having several different ring types were evaluated for their acetylcholinesterase enzyme (AChE) inhibitory activity. The alkaloid 1- O-acetyllycorine (IC50 : 0.96 +/- 0.04) showed significant AChE inhibitory activity. In addition, crinine (IC50 : 461 +/- 14), crinamidine (IC50 : 300 +/- 27), epivittatine (IC50 : 239 +/- 9), 6-hydroxycrinamine (IC50 : 490 +/- 7), N-desmethyl-8alpha-ethoxypretazettine (IC50 : 234 +/- 13) N-desmethyl-8beta-ethoxypretazettine (IC50 : 419 +/- 8), lycorine (IC50 : 213 +/- 1), and 1,2-di- O-acetyllycorine (IC50 : 211 +/- 10) had weak activity. Lycorine-type alkaloids were the most active alkaloids with 1- O-acetyllycorine exhibiting inhibitory effects two-fold more potent than that of galanthamine.
143 citations
TL;DR: Three alkaloids, lycorine, homolycorine and 2- O-acetylly Corine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis and demonstrate that trisphaeridine, lyCorine, Homolycorines and haemanthamine possess high antiretroviral activities.
Abstract: Three alkaloids, lycorine, homolycorine and 2- O-acetyllycorine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis The alkaloids obtained from L vernum and from other Amaryllidaceae species were studied in vitro for HIV-1 replication inhibitory activity on MT4 cells The cytotoxicity of the compounds in uninfected cells was evaluated by using the MTT assay and the [ (3)H]thymidine incorporation test The antiviral activities were determined by means of the p24 antigen assay and solid-phase reverse transcriptase testing The results demonstrate that trisphaeridine, lycorine, homolycorine, and haemanthamine possess high antiretroviral activities (IC (50) = 04 - 73 microg/mL), accompanied by low therapeutic indices (TI (50) = 13 - 19)
137 citations
TL;DR: The inhibitory potential of the pure metabolites against plasmodial enoyl-ACP reductase (FabI), which is the key regulator of type II fatty acid synthases (FAS-II) in P. falciparum, was also assessed.
Abstract: Anti-plasmodial activity-guided fractionation of Phlomis brunneogaleata (Lamiaceae) led to the isolation of two new metabolites, the iridoid glycoside, brunneogaleatoside and a new pyrrolidinium derivative (2S,4R)-2-carboxy-4-(E)-p-coumaroyloxy-1,1-dimethylpyrrolidinium inner salt [(2S,4R)-1,1-dimethyl-4-(E)-p-coumaroyloxyproline inner salt]. Moreover, a known iridoid glycoside, ipolamiide, six known phenylethanoid glycosides, verbascoside, isoverbascoside, forsythoside B, echinacoside, glucopyranosyl-(1→Gi-6)-martynoside and integrifolioside B, two flavone glycosides, luteolin 7-O-β-D-glucopyranoside (10) and chrysoeriol 7-O-β-D-glucopyranoside (11), a lignan glycoside liriodendrin, an acetophenone glycoside 4-hydroxyacetophenone 4-O-(6′-O-β-D-apiofuranosyl)-β-D-glucopyranoside and three caffeic acid esters, chlorogenic acid, 3-O-caffeoylquinic acid methyl ester and 5-O-caffeoylshikimic acid were isolated. The structures of the pure compounds were elucidated by means of spectroscopic methods (UV, IR, MS, 1D and 2D NMR, [α]D) and X-ray crystallography. Compounds 10 and 11 were determined to be the major anti-malarial principles of the crude extract (IC50 values of 2.4 and 5.9 μg/mL, respectively). They also exhibited significant leishmanicidal activity (IC50 = 1.1 and 4.1 μg/mL, respectively). The inhibitory potential of the pure metabolites against plasmodial enoyl-ACP reductase (FabI), which is the key regulator of type II fatty acid synthases (FAS-II) in P. falciparum, was also assessed. Compound 10 showed promising FabI inhibiting effect (IC50 = 10 μg/mL) and appears to be the first anti-malarial natural product targeting FabI of P. falciparum.
125 citations
TL;DR: Findings indicate that CE and AC have an anti-inflammatory property that is brought about by inhibition of NO synthesis and thus facilitates ulcer healing.
Abstract: In this study, the effects of Centella asiatica water extract (CE) and its active constituent, asiaticoside (AC), on the expression and activity of inducible nitric oxide synthase (iNOS) during gastric ulcer healing in rats were investigated. CE was prepared from Centella asiatica dry plant and the concentration of AC in CE was quantitatively determined with the use of high performance liquid chromatography analysis. Different concentrations of CE (0.10 g/kg and 0.25 g/kg) and AC (5 mg/kg and 10 mg/kg) were orally administered to rats with acetic acid-induced gastric ulcers. They were found to reduce the size of the ulcers at days 1, 3 and 7 after ulcer induction in a dose-dependent manner, with a concomitant attenuation of iNOS activity and protein expression at the ulcer tissues. The levels of nitrite and nitrate (NO(X)-), the stable end-products of nitric oxide (NO), in the gastric ulcer tissues were also decreased. N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of iNOS, was found to produce similar but more potent inhibition on iNOS activity at a dose of 0.1 mg/kg. These findings indicate that CE and AC have an anti-inflammatory property that is brought about by inhibition of NO synthesis and thus facilitates ulcer healing.
119 citations
TL;DR: In conclusion, inhibition of both ROS production and firm adhesion by neutrophils has no significant cytotoxic effect that could give these drugs the potential to be anti-inflammatory agents for the clinical treatment.
Abstract: We have previously shown that a concentrated ethanol extract of the fruiting bodies of Antrodia camphorata exhibited immunomodulating effects in human leukocytes and fourteen compounds including zhankuic acids A, B, C, and antcin K were identified in the extract. In this study, an acute cellular model in isolated peripheral human neutrophils was established to elucidate the anti-inflammatory effects of these compounds. Reactive oxygen species (ROS) production and firm adhesion by neutrophils display two important responses during inflammation. To evaluate whether these compounds could prevent inflammatory responses by neutrophils, their effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate-13-acetate (PMA)-activated peripheral human neutrophils were examined. Pretreatment with 1 - 25 microM of zhankuic acids A, B, C, or antcin K concentration-dependently diminished fMLP- or PMA-induced ROS production, as measured by a lucigenin-amplified chemiluminescence, with IC (50) (microM) around 5 - 20 microM. Zhankuic acids A, B, C, or antcin K also effectively inhibited the fMLP- or PMA-induced firm adhesion without interfering with the up-expression of surface Mac-1 (CD11b/CD18), a beta2 integrin mediating the firm adhesion of neutrophils to endothelium. The anti-inflammatory actions of these drugs were not due to cytotoxic effects because no significant difference in cell viability was observed compared to vehicle control. These data suggest that inhibition of both ROS production and firm adhesion by neutrophils has no significant cytotoxic effect that could give these drugs the potential to be anti-inflammatory agents for the clinical treatment.
TL;DR: Two compounds evaluated for their antibacterial and efflux inhibitory activity against a wild-type and three multidrug-resistant strains of Staphylococcus aureus paradoxically stimulated efflux.
Abstract: Epicatechin gallate (1) and epigallocatechin gallate (2) were evaluated for their antibacterial and efflux inhibitory activity against a wild-type and three multidrug-resistant (MDR) strains of Staphylococcus aureus. Compound 2 was more active than 1 based on minimum inhibitory concentrations (MICs; 32-64 versus 64->512 microg/mL, respectively). When incorporated into the growth medium at 20 microg/mL, both compounds exhibited a four-fold potentiation of the activity of norfloxacin against a norfloxacin-resistant strain of S. aureus overexpressing the NorA multidrug efflux pump. Against this strain 1 was moderately more potent than 2 as an inhibitor of ethidium efflux, but at < or = 20 microM both compounds paradoxically stimulated efflux. This phenomenon has not been encountered previously in the analysis of inhibitors of multidrug efflux.
TL;DR: Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12. 5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive.
Abstract: From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive.
TL;DR: It was found that the origin, purity and preparation methods contributed to the differences observed in prepared chamomile extracts and NMR-based metabolomics enabled the elucidation of the molecular information embedded in the spectra responsible for the observed variability.
Abstract: In order to improve the accuracy and consistency of control phytomedicine preparations worldwide, regulatory authorities are requesting research into new analytical methods for the stricter standardisation of phytomedicines. Such methods have to be both objective and robust, and should address the reproducibility of the content of the chemical profiles. NMR-based metabolomics, which combines high-resolution (1)H-NMR spectroscopy with chemometric analysis, has been employed as an innovative way to meet those demands. In this paper, chamomile flowers from three different geographical regions, namely, Egypt, Hungary and Slovakia were characterised using 1H-NMR spectroscopy followed by principal component analysis. It was found that the origin, purity and preparation methods contributed to the differences observed in prepared chamomile extracts. In addition, this method also enabled the elucidation of the molecular information embedded in the spectra responsible for the observed variability. The metabolomic strategy employed in the current study should provide an efficient tool for the quality control and authentication of phytomedicines.
TL;DR: Besides the chemical composition, the estrogenic and anti-platelet aggregation activities of DBT were determined in different groups of the extraction, and the results of bioassays were in line with the amounts of the analyzed chemical ingredients.
Abstract: Danggui Buxue Tang (DBT) is a simple decoction, having about 800 years of usage in China to treat menopausal irregularity in women, which contains two herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). Traditionally, boiling water has been used for preparing DBT; however, the optimized conditions of extraction have not yet been determined. Here, the amounts of Radix Astragali-derived astragaloside IV, calycosin, formononetin, and Radix Angelicae Sinensis-derived ferulic acid and ligustilide were determined in DBT, which were extracted according to an orthogonal array experimental design having three variable parameters: extraction time, extraction volume and number of repeats of the extraction. Our results suggest that extraction time and number of repeats of the extraction are two crucial factors, while extraction volume is a subordinate factor. The optimized conditions for extraction were therefore established. Besides the chemical composition, the estrogenic and anti-platelet aggregation activities of DBT were determined in different groups of the extraction, and the results of bioassays were in line with the amounts of the analyzed chemical ingredients. The results provide a model system for establishing the quality assurance of the herbal preparation.
TL;DR: An extract from stem bark of Cinnamomum cassia Blume was discovered to have an inhibitory effect on LPS-induced NF-KB transcriptional activity, which was determined using macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter construct containing four copies of the NF- KB binding KB sequence.
Abstract: Nuclear factor (NF)-cB is a transcription factor regulating the expression of inflammatory and immune genes. In the present study, an extract from stem bark of Cinnamomum cassia Blume(Lauraceae) was discovered to have an inhibitory effect on LPS-induced NF-KB transcriptional activity, which was determined using macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter construct containing four copies of the NF-KB binding KB sequence. Following activity-guided fractionation, trans-cinnamaldehyde and 2-methoxycinnamaldehyde were identified as the NF-KB inhibitors from C cassia with IC50 values of 43 MM and 31 pM, respectively. As a positive control, caffeic acid phenethyl ester (CAPE) showed an IC50 value of 2 uM on NF-KB transcriptional activity. Both trans-cinnamaldehyde and 2-methoxycinnamaldehyde inhibited LPS-induced DNA binding activity of NF-KB in addition to NF-KB transcription-al activity.
TL;DR: Bioassay-guided fractionation of the ethanol extract of Ficus racemosa resulted in the identification of a new compound (rel)-4,6-dihydroxy-5-[3-methyl-(E)-propenoic acid-3-yl]-7-beta-glucopyranosyl (racemosic acid), which demonstrated a strong antioxidant activity to scavenge ABTS free radical cations.
Abstract: Bioassay-guided fractionation of the ethanol extract of Ficus racemosa resulted in the identification of a new compound (rel)-4,6-dihydroxy-5-[3-methyl-(E)-propenoic acid-3-yl]-7-beta-glucopyranosyl-[2alpha,3beta-dihydrobenzofuran]-(3,2: b)-[4alpha,5beta-dihydroxy-6alpha-hydroxymethyltetrahydropyran] (racemosic acid). Racemosic acid showed potent inhibitory activity against COX-1 and 5-LOX in vitro with IC50 values of 90 and 18 microM, respectively. Racemosic acid also demonstrated a strong antioxidant activity to scavenge ABTS free radical cations with an IC50 value of 19 microM. In addition, cytotoxic effects of the extracts of F. racemosa were investigated in vitro using the ATP-based luminescence assay and results showed no cytotoxicity on the cell lines skin fibroblasts (1BR3), human Caucasian hepatocyte carcinoma (Hep G2) and human Caucasian promyelocytic leukaemia (HL-60). Bergenin was also isolated from the same active fraction.
TL;DR: Results revealed that some sulfated polysaccharides from green algae should be promising candidates of antiviral agents which might act on different stages in the virus replication cycle.
Abstract: In order to evaluate the potency of novel antiviral drugs, 11 natural sulfated polysaccharides (SPs) from 10 green algae ( Enteromorpha compressa, Monostroma nitidum, Caulerpa brachypus, C. okamurai, C. scapelliformis, Chaetomorpha crassa, C. spiralis, Codium adhaerens, C. fragille, and C. latum) and 4 synthetic sulfated xylans (SXs) prepared from the beta-(1,3)-xylan of C. brachypus, were assayed for anti-Herpes simplex virus type 1 (HSV-1) activity. Except for one from E. compressa, all SPs showed potent anti-HSV-1 activities with 50 % inhibitory concentrations (IC (50)) of 0.38 - 8.5 microg/mL, while having low cytotoxicities with 50 % inhibitory concentrations of >2900 microg/mL. Anti-HSV-1 activities of SXs were dependent on their degrees of sulfation. To delineate the drug-sensitive phase, 4 polysaccharides, which showed potent anti-HSV-1 activities, were applied to time-of-addition experiments. Among the polysaccharides tested, 3 polysaccharides (SX4, SP4 from C. brachypus, and SP11 from C. latum) showed strong anti-HSV-1 activities with IC (50) of 6.0, 7.5, and 6.9 microg/mL, respectively, even when added to the medium 8 h post-infection. These experiments demonstrated that some sulfated polysaccharides not only inhibited the early stages of HSV-1 replication, such as virus binding to and penetration into host cells, but also interfered with late steps of virus replication. These results revealed that some sulfated polysaccharides from green algae should be promising candidates of antiviral agents which might act on different stages in the virus replication cycle.
TL;DR: The isolated compounds, except for diospongin A, exerted potent inhibitory activities on bone resorption induced by parathyroid hormone in a bone organ culture system.
Abstract: Bioassay-guided fractionation of the water extract of the rhizomes of Dioscorea spongiosa led to the isolation and identification of new diarylheptanoids, diospongins A - C, together with three known lignans. Their structures, including absolute stereochemistry, were determined by analyses of NMR data, chemical conversions and CD spectrum. The isolated compounds, except for diospongin A, exerted potent inhibitory activities on bone resorption induced by parathyroid hormone in a bone organ culture system.
TL;DR: The 80 % aqueous acetone extract from the fruit of Piper chaba was found to show protective effects on ethanol- and indomethacin-induced gastric lesions in rats, and four new amides named piperchabamides were isolated.
Abstract: The 80 % aqueous acetone extract from the fruit of Piper chaba was found to show protective effects on ethanol- and indomethacin-induced gastric lesions in rats. From the aqueous acetone extract, four new amides named piperchabamides A ( 1), B ( 2), C ( 3), and D ( 4) were isolated, and their structures were determined on the basis of chemical and physicochemical evidence. In addition, the gastroprotective effects of the principal constituents, piperine ( 5), piperanine ( 6), pipernonaline ( 7), dehydropipernonaline ( 8), piperlonguminine ( 9), retrofractamide B ( 10), guineensine ( 11), N-isobutyl-(2 E,4 E)-octadecadienamide ( 12), N-isobutyl-(2 E,4 E,14 Z)-eicosatrienamide ( 13), and methyl piperate ( 14), were examined. As a result, compounds 5 - 10 and 12 - 14 significantly inhibited ethanol-induced gastric lesions at a dose of 25 mg/kg, p. o., while 5, 7, 8, 10, 12, and 13 also significantly inhibited indomethacin-induced gastric lesions at the same dose.
TL;DR: Geniposide showed anti-angiogenic activity in a dose-dependent manner and exhibited an inhibitory effect in the range of 25-100 microM on the growth of the transformed NIH3T3 cell line.
Abstract: The EtOH extract of gardenia (Gardenia jasminoides Ellis) fruits was previously found to possess potent anti-angiogenic activity in the chick embryo chorioallantoic membrane (CAM) assay. Bioassay-guided fractionation and purification of the EtOH extract yielded an active anti-angiogenic compound, which was determined to be an iridoid glucoside, geniposide, by spectral analyses. Geniposide showed anti-angiogenic activity in a dose-dependent manner. It also exhibited an inhibitory effect in the range of 25-100 microM on the growth of the transformed NIH3T3 cell line.
TL;DR: A possible justification for those medicinal plants containing iridoid glycoside that have been used for the treatment of inflammation is indicated, implying that there is no influence on the cAMP level in other cell systems.
Abstract: To elucidate a possible mechanism for the anti-inflammatory action of iridoid glycosides, the effects of both aucubin (AU) and its hydrolyzed product (H-AU) by beta-glucosidase treatment were studied on the production of TNF-alpha in RAW 264.7 cells. H-AU suppressed the production of both mRNA for TNF-alpha and subsequent TNF-alpha protein in the culture, but AU did not. The production of TNF-alpha protein was inhibited in a dose-dependent manner with an IC (50) of 9.2 microM. In addition, treatment with H-AU blocked both the I-kappa B alpha degradation and the translocation of NF-kappa B from the cytosol fraction to the nuclear fraction (55 % inhibition) in the culture. However, treatment with H-AU did not affect the intracellular level of cAMP formed by forskolin treatment in human monocytes U937 culture, implying that there is no influence on the cAMP level in other cell systems. The present study indicates a possible justification for those medicinal plants containing iridoid glycoside that have been used for the treatment of inflammation.
TL;DR: Antitubercular bioassay-guided fractionation of the n-hexane- and CH (2)Cl (2)-soluble extracts of the above-ground biomass and roots of Valeriana laxiflora led to the isolation of a new iridolactone, (4R,5R,7S,8S,9S)-7-hydroxy-8-hydroxymethyl-4-methyl-perhydrocyclopenta.
Abstract: Antitubercular bioassay-guided fractionation of the n-hexane- and CH (2)Cl (2)-soluble extracts of the above-ground biomass and roots of Valeriana laxiflora led to the isolation of a new iridolactone, (4R,5R,7S,8S,9S)-7-hydroxy-8-hydroxymethyl-4-methyl-perhydrocyclopenta[ c]pyran-1-one ( 1), and a new lignan, (+)-1-hydroxy-2,6-bis- epi-pinoresinol ( 2), along with eleven known compounds, betulin ( 3), betulinic acid ( 4), 5,7-dihydroxy-3,6,4'-trimethoxyflavone ( 5), 23-hydroxyursolic acid ( 6), oleanolic acid ( 7), tricin ( 8), ursolic acid ( 9), ferulic acid, (+)-1-hydroxypinoresinol, prinsepiol, and 5,7,3'-trihydroxy-4'-methoxyflavone. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic evidence. The absolute stereochemistry of 1 was determined by chemical transformations and Mosher ester procedures. In a microplate alamar blue assay against Mycobacterium tuberculosis, compounds 2 - 9 exhibited minimum inhibitory concentrations (MIC) of 15.5 - 127 microg/mL, while the other isolates were regarded as inactive (MIC > 128 microg/mL). In addition, all the isolates were tested for cytotoxicity against African green monkey Vero cells in order to evaluate their selectivity potential.
TL;DR: Biochemical experiments showed that actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines, which may explain, at least in part, the effects observed on cancer cells and on trypanosomes.
Abstract: Cassytha filiformis (Lauraceae), a widely distributed parasitic plant, contains several aporphine alkaloids and is often used in African folk medicine to treat cancer, African trypanosomiasis and other diseases. In a previous investigation, we showed that the alkaloid plant extract and the isolated aporphines possessed in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity of the alkaloid extract (IC50 = 2.2 microg/mL) and its three major aporphine alkaloids (actinodaphnine, cassythine, and dicentrine) on Trypanosoma brucei brucei as well as four related commercially available aporphines (bulbocapnine, glaucine, isocorydine, boldine). Only the three alkaloids from Cassytha filiformis were active on the trypanosomes in vitro (IC50 = 3-15 microM). Additionally, we compared the cytotoxicity of these seven compounds on HeLa cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2 microM) in the series. In order to elucidate their mechanism of action, the binding mode of these molecules to DNA was studied by UV absorption, circular and linear dichroism spectroscopy. The results of the optical measurements indicated that all seven aporphines effectively bind to DNA and behave as typical intercalating agents. Biochemical experiments showed that actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines. These interactions with DNA may explain, at least in part, the effects observed on cancer cells and on trypanosomes.
TL;DR: The complete structure of 9'-( O-methyl)protocetraric acid was elucidated using HSQC and HMBC spectral data and was shown to induce apoptosis of murine leukaemia L1210 cells in a dose- and time-dependent manner.
Abstract: The depsidone 9'-( O-methyl)protocetraric acid was isolated from the lichen Cladonia convoluta (Lam.) Anders along with the known (-)-usnic acid and fumarprotocetraric acid. The complete structure of 9'-( O-methyl)protocetraric acid was elucidated using HSQC and HMBC spectral data. (-)-Usnic acid was the only compound to display a moderate cytotoxic activity on various cancer cell lines (IC (50) = 6, 12.1, 15.8, 17.8, 8.2 and 6.8 microg/mL on L1210, 3LL, DU145, MCF7, K-562 and U251, respectively). This compound was also shown to induce apoptosis of murine leukaemia L1210 cells in a dose- and time-dependent manner.
TL;DR: The elicitor function of Ag (+) in the hairy root culture was validated by its ability to induce the characteristic elicitor responses of plants, the increase in cross-cell membrane ion fluxes and the production of reactive oxygen species.
Abstract: Ag (+) was employed as an abiotic elicitor to stimulate the secondary metabolite production in hairy root culture of Salvia miltiorrhiza, a valuable herbal plant. The addition of Ag (2)S (2)O (3) at 15 - 40 microM to the culture between 12 and 22 days post inoculation resulted in more than 2-fold increase in the yields of the three diterpenoid tanshinones, tanshinone I, tanshinone IIA and cryptotanshinone. This stimulating effect was dependent on the Ag (+) dose, the day of Ag (+) addition to the culture and the tanshinone species, while the total yield of the three tanshinones (TT) was mainly dependent on the Ag (+) dose, with the highest being attained at 30 microM. The Ag (+) treatment also caused a dose-dependent inhibition of hairy root growth. Sucrose feeding or medium renewal before the addition of Ag (+) to the culture effectively prevented the growth inhibition, and significantly increased the biomass concentration and volumetric tanshinone yield. With combined medium renewal and Ag (+) treatment, in particular, the TT yield was increased 6.6-fold relative to that of the control (55.7 mg/L versus 7.3 mg/L). The elicitor function of Ag (+) in the hairy root culture was validated by its ability to induce the characteristic elicitor responses of plants, the increase in cross-cell membrane ion fluxes and the production of reactive oxygen species.
TL;DR: The methanolic extract from the tubers of Gymnadenia conopsea showed an antiallergic effect on ear passive cutaneous anaphylaxis reactions in mice and three new dihydrophenanthrenes, gymconopins A, B, and C, were isolated together with 10 known phenanthrene and stilbene constituents.
Abstract: The methanolic extract from the tubers of Gymnadenia conopsea showed an antiallergic effect on ear passive cutaneous anaphylaxis reactions in mice. From the methanolic extract, three new dihydrophenanthrenes, gymconopins A ( 1), B ( 2), and C ( 3), and a new dihydrostilbene, gymconopin D ( 4), were isolated together with 10 known phenanthrene and stilbene constituents. The structures of the new compounds were determined on the basis of physicochemical evidence. Next, the inhibitory effects of the principal constituents on the release of beta-hexosaminidase, as a marker of degranulation, in RBL-2H3 cells were examined and five phenanthrenes, gymconopin B ( 2), 4-methoxy-9,10-dihydrophenanthrene-2,7-diol ( 6), 1-(4-hydroxybenzyl)-4-methoxyphenanthrene-2,7-diol ( 7), 1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol ( 8), and blestriarene A ( 9), and six dihydrostilbenes, gymconopin D ( 4), batatacin III ( 10), 3'- O-methylbatatacin III ( 11), 3,3'-dihydroxy-2-(4-hydroxybenzyl)-5-methoxybibenzyl ( 12), 3',5-dihydroxy-2-(4-hydroxybenzyl)-3-methoxybibenzyl ( 13), and 3,3'-dihydroxy-2,6-bis(4-hydroxybenzyl)-5-methoxybibenzyl ( 14) were found to inhibit the antigen-induced degranulation by 65.5 to 99.4 % at 100 microM in RBL-2H3 cells.
TL;DR: As part of a study on chemical constituents of Camptotheca species, one new natural camptothecin analogue (2), two new alkaloids (3, 4), one new ellagic acid analogue (5), and 19 known compounds have been isolated from the root bark, stem bark, fruits, and leaves of CamPTotheca Decaisne.
Abstract: As part of a study on chemical constituents of Camptotheca species, one new natural camptothecin analogue (2), two new alkaloids (3, 4), one new ellagic acid analogue (5), and 19 known compounds (1, 6-23) have been isolated from the root bark, stem bark, fruits, and leaves of Camptotheca acuminata Decaisne. The structures of 2-5 were determined from spectral data to be 10-methoxy-20-O-acetylcamptothecin (2), 20-O-beta-glucopyranosyl 18-hydroxycamptothecin (3), 20-formylbenz indolizino [1,2-b]quino-line-11(13H)-one (4), and 3,4-methylenedioxy-3'-O-methyl-5'-hydroxyellagic acid (5).
TL;DR: Three substances of Dictyota pfaffii afforded the rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2, 6-dolABelladiene and the new 10-acetoxy-7,8-di-Hydroxy- 2,6-Dolablladiene, which showed strong anti-HSV-1 activity in vitro but only 3 inhibited the reverse transcriptase enzyme of HIV-
Abstract: Specimens of Dictyota pfaffii from Atol das Rocas, Northeast Brazil, afforded the rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2, 6-dolabelladiene (1) and the new 10-acetoxy-8,18-di-hydroxy-2,6-dolabelladiene (2). Reduction of 1 yielded 8,10,18-trihydroxy-2,6-dolabelladiene (3), also present in the crude ex-tract of D. pfaffii. All three structures were assigned by 1D and 2D NMR spectral data. These substances showed strong anti-HSV-1 activity in vitro but only 3 inhibited the reverse transcriptase enzyme of HIV-1.
TL;DR: Detailed kinetics of BAs after oral dosing of an extract are revealed and a profound effect of food intake on the pharmacokinetic profile of the BAs is demonstrated.
Abstract: In this study we investigated the effects of concomitant food intake on the bioavailability of distinct boswellic acids (BAs) from the test preparation BSE-018, a dry extract from Boswellia serrata gum resin. In a randomised, open, single-dose, two-way crossover study, healthy male subjects received three capsules of BSE-018 equivalent to 786 mg dry extract of Boswellia serrata gum resin either in the fasted state or together with a standardised high-fat meal. BA plasma concentrations were analysed for up to 60 h after oral dosing by reversed phase HPLC. As compared to the fasted state (treatment A), the administration of BSE-018 concomitantly with a high-fat meal (treatment B) led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA), 11-keto-beta-boswellic acid (KbetaBA) and acetyl-11-keto-beta-boswellic acid (AKbetaBA). Plasma levels of both acetyl-alpha-boswellic acid (AalphaBA) and alphaBA became only detectable when administered with treatment B, i.e., the high-fat meal. Accordingly, pharmacokinetic data could be calculated for betaBA, KbetaBA and AKbetaBA (treatment A) and for betaBA, KbetaBA, AKbetaBA, alphaBA, and AalphaBA (treatment B). For the first time these data reveal detailed kinetics of BAs after oral dosing of an extract and demonstrate a profound effect of food intake on the pharmacokinetic profile of the BAs. This finding should be very important whenever BAs would be considered for therapeutic use.