<Emphasis Type="Italic">Vatairea macrocarpa</Emphasis> (Leguminosae) lectin activates cultured macrophages to release chemotactic mediators

The lectin from the legume Vatairea macrocarpa is a galactose/N-acetylgalactosamine binding protein that induced cellular inflammatory response mediated by resident cells. This study investigated which inflammatory mediators would be released from lectin-activated cells. The intraperitoneal injection in rats of the supernatant from cultured macrophages, but not from mast cells, stimulated with lectin induced a time- and dose-dependent release of a neutrophil chemotactic factor, termed MNCF-VML. Pharmacological modulation with dexamethasone inhibited both the lectin-induced chemotactic activity in vivo and also the lectin-induced release of MNCF-VML into the supernatant of cultured macrophages. Cyclooxygenase and lipoxygenase metabolites are apparently not involved in the action of this factor or its release, since indomethacin or MK886 were unable to affect the lectin response. The molecular weight of MNCF-VML was found to be greater than 5 kDa, which led to the investigation of which cytokine(s) could be involved by the following approaches: (a) treatment of animals with antiserum to tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, or IL-8 before intraperitoneal injection of lectin and (b) addition of antiserum to TNF-α, IL-1, or IL-8 to the supernatant of lectin-stimulated macrophages before intraperitoneal administration. Antiserum to TNF-α, but not IL-1 nor IL-8, inhibited the neutrophil migration induced either by lectin or MNCF-VML. Our data suggest that neutrophil migration induced by V. macrocarpa lectin occurs via the release of cytokines such as TNF-α by macrophages. Thus, this lectin may represent an important tool to better understand pathological situations where an excess of leukocytes at inflammatory sites causes tissue injury.     

A new <Emphasis Type="Italic">Erythrina</Emphasis> alkaloid from <Emphasis Type="Italic">Erythrina herbacea</Emphasis>

A new Erythrina alkaloid, 10-hydroxy-11-oxoerysotrine (1), has been isolated from the flowers of Erythrina herbacea together with five known compounds: erytharbine (2), 10,11-dioxoerysotrine (3), erythrartine (4), erysotramidine (5) and erysotrine-N-oxide (6). The structure of the new compound was elucidated on the basis of its spectral data, including 2-D NMR and mass (MS) spectra. The new compound is a rare C-10 oxygenated Erythrina alkaloid. The antioxidant activities of the isolated compounds 1–6 were evaluated by scavenging with peroxynitrite.     

Alkaloids from the seeds of <Emphasis Type="Italic">Peganum harmala</Emphasis> showing antiplasmodial and vasorelaxant activities

Bioassay-guided purification from the seeds of Peganum harmala led to the isolation of harmine (1), harmaline (2), vasicinone (3), and deoxyvasicinone (4). Harmine (1) and harmaline (2) showed a moderate in vitro antiplasmodial activity against Plasmodium falciparum. Quinazoline alkaloid, vasicinone (3), showed a vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.     

Studies on the chemical constituents from the roots of <Emphasis Type="Italic">Platycodon grandiflorum</Emphasis>

Three known monodesmosidic saponins: 3-O--d-glucopyranosyl-2,3,16,23,24-pentahydroxyolean-12-ene-28-oic acid, 3-O--d-glucopyranosyl polygalacic acid, and 3-O--d-glucopyranosyl-(13)--d-glucopyranosyl polygalacic acid; and two known nonsaponin compounds: a mixed compound of n-tetracosanoic acid (lignoceric acid), n-hexacosanoic acid (cerotic acid), and n-octacosanoic acid, and -monopalmitin; were isolated for the first time from the root of Platycodon grandiflorum A. DC. together with another seven known compounds: platycoside G₁ (3-O--d-glucopyranosyl-(16)--d-glucopyranosyl-(16)--d-glucopyranosyl-2,3,16,23,24-pentahydroxyolean-12-ene-28-oic acid 28-O--d-xylopyranosyl-(14)--l-rhamnopyranosyl-(12)--l-arabinopyranoside), deapio-platycodin D, Polygalacin D, deapio-platycodin D₃, platycoside A, -spinasterol, and -spinasteryl-3-O--d-glucopyranoside. Alkaline hydrolysis of platycoside G₁ afforded a new monodesmosidic prosaponin: 3-O--d-glucopyranosyl-(16)--d-glucopyranosyl-(16)--d-glucopyranosyl-2,3,16,23,24-pentahydroxyolean-12-ene-28-oic acid. Their chemical structures were elucidated on the basis of their spectral data and chemical evidence.     

Antitubercular triterpenes and phytosterols from <Emphasis Type="Italic">Pandanus tectorius </Emphasis>Soland. var. <Emphasis Type="Italic">laevis</Emphasis>

Bioassay-guided chromatographic purification of the antitubercular chloroform extract of Pandanus tectorius Soland. var. laevis leaves afforded a new tirucallane-type triterpene, 24,24-dimethyl-5β-tirucall-9(11),25-dien-3-one (1), squalene and a mixture of the phytosterols stigmasterol and β-sitosterol. Microplate Alamar Blue Assay (MABA) showed that 1 inhibited the growth of Mycobacterium tuberculosis H₃₇Rv with a MIC of 64 μg/mL, while squalene and the sterol mixture have MICs of 100 and 128 μg/mL, respectively.     

Chemical constituents of <Emphasis Type="Italic">Hypericum erectum</Emphasis> Thunb.

Twenty-two known constituents, including four xanthones, nine flavonoids and nine phenolic glycosides, were isolated from Hypericum erectum Thunb. Their structures were elucidated on the basis of spectral evidence.     

<Emphasis Type="Italic">In Vitro</Emphasis> antioxidant and anti-inflammatory activities of Jaceosidin from <Emphasis Type="Italic">Artemisia princeps</Emphasis> Pampanini <Emphasis Type="Italic">cv.</Emphasis> Sajabal

Oxidized low-density lipoprotein (oxLDL) plays a key role in the inflammatory processes of atherosclerosis. Jaceosidin isolated from the methanolic extracts of the aerial parts of Artemisia princeps Pampanini cv. Sajabal was tested for antioxidant and anti-inflammatory activities. Jaceosidin inhibited the Cu²⁺-mediated LDL oxidation with IC₅₀ values of 10.2 μM in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. The antioxidant activities of jaceosidin were exhibited in the conjugated diene production, relative electrophoretic mobility, and apoB-100 fragmentation on copper-mediated LDL oxidation. Jaceosidin also inhibited the generation of reactive oxygen species (ROS) concerning in regulation of NF-κB signaling. And jaceosidin inhibited nuclear factor-kappa B (NF-κB) activity, nitric oxide (NO) production, and suppressed expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.     

<Emphasis Type="Italic">Perilla frutescens</Emphasis> var. <Emphasis Type="Italic">frutescens</Emphasis> in northern Laos

Twenty-eight samples of mericarps of Perilla frutescens var. frutescens were collected through fieldwork performed in Phongsali and Xieng Khouang provinces in northern Laos. No perilla samples were collected from Savannakhet province in the south although more than 20 sites were investigated. Perilla plants are mostly grown mixed with dry-paddy rice by slash-and-burn cultivation in Laos. The most popular local name for perilla mericarps in the area was “Ma Nga Chan”. Weight of 1,000 grains and hardness of the mericarps were measured, and all mericarps were found to be large (weight of 1,000 grains around 2 g) and soft (limit load weight under 300 g), which were preferred for culinary use in Laos. The composition of the essential oils obtained from the herbaceous plants raised from the mericarps was divided into five types, perillaketone, elemicine plus myristicine, shisofuran, piperitenon, and myristicine, and GC–MS analysis of these Laotian perilla samples showed that they were similar to those of corresponding types of known Japanese perilla strains. One of the shisofuran-type perilla contained large amounts of putative α-naginatene, which is likely to be an intermediate of the biosynthesis of naginataketone. The farmers' indifference to the oil type of the leaf seems to leave Laotian perilla as a good genetic resource for studies of the biosynthesis of oil compounds.     

Crystal structure of tuguaconitine,a diterpene alkaloid from <Emphasis Type="Italic">Aconitum sibiricum</Emphasis>

The three-dimensional structure of a natural product, tuguaconitine (C23H35NO7) from Aconitumrn sibiricum was determined by single crystal X-ray diffraction analysis. The compound was recrystallized from a methanol solution into orthorhombic crystal system, with a = 18.093(4), b = 12.075(11), c = 9.824(4) A, Dm = 1.35, Dx= 1.354 g/cm3, space group P2(1)2(1)2(1), and Z=4. The structure was solved by direct method and refined by least-squares procedure to the final R value of 0.046 for 1495 observed reflections with I > or = 2sigma(I). Aconitines are diterpene alkaloid composed of six rings. In the molecule, two 6-membered rings have stable chair conformation, but other two 6-membered rings have unstable boat conformation because of their bonding strain and hydrogen bonds. Based on the three-dimensional structure of tuguaconitine, we suggest another 2D-diagram for the compound which is far better in imagination of the spatial shape of the molecule than the ordinary one.     

Suppressive effects of novel derivatives prepared from <Emphasis Type="Italic">Aconitum</Emphasis> alkaloids on tumor growth

Summary  Little information has so far been reported regarding the antiproliferative properties of Aconitum alkaloids against human tumor cells despite of their intense toxicities. In the present study, the antitumor properties and radiation sensitizing effects were investigated by various types of novel derivatives prepared from Aconitum alkaloids. The antitumor properties were investigated against human tumor cell lines, A172, A549, HeLa and Raji, respectively, by a cell growth, a clonogenic assay, cell cycle distribution, cell cycle related molecules and γH2AX expression. The novel compounds derived from C₂₀-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C₁₉-norditerpenoid alkaloids and their derivatives showed either no effect or only a slight effect. One of the compounds also showed radiosensitizing properties on A549 cells. These effects are not related to either the cell cycle distribution, the enhancement of apoptosis or the γH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.     

Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

<Emphasis Type="Italic">Pulsatilla</Emphasis> saponin D: The antitumor principle from<Emphasis Type="Italic">Pulsatilla koreana</Emphasis>

By bioassay-guided separation, an already known saponin, Pulsatilla saponin D was isolated from the root of Pulsatilla koreana Nakai as a antitumor component when evaluated by in vivo antitumor activity as well as in vitro cytotoxic activity test. It showed potent inhibition rate of tumor growth (IR, 82%) at the dose of 6.4 mg/kg on the BDF1 mice bearing LLC cells.     

Cytotoxic constituents of <Emphasis Type="Italic">Amanita subjunquillea</Emphasis>

As part of our systematic study of Korean toxic mushrooms, we have investigated the constituents of Amanita subjunquillea. The column chromatographic separation of the MeOH extract of A. subjunquillea led to the isolation of four ergosterols, two cerebrosides and four cyclopeptides. Their structures were determined by spectroscopic methods to be (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9,22-triene-3beta-ol (1), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (2), (22E,24R)-5alpha,6alpha-epoxyergosta-8,22-diene-3beta,7beta-diol (3), (24S)-ergost-7-en-3beta-ol (4), 8,9-dihydrosoyacerebroside I (5), soyacerebroside I (6), beta-amanitin (7), phalloin (8), alpha-amanitin (9), and phalloidin (10). The compounds 1-6 and 8 were isolated for the first time from this mushroom. The isolated compounds were evaluated for the cytotoxicity against A549, SK-OV-3, SK-MEL-2 and HCT15 cells. Compound 9 exhibited significant cytotoxic activity against A549, SK-OV-3, SK-MEL-2 and HCT15 with ED(50) values of 1.47, 0.26, 1.57 and 1.32 microM, respectively.     

A new lignan from <Emphasis Type="Italic">Aphanamixis polystachya</Emphasis>

A new lignan, polystachyol (1), two lignan glycosides, lyoniside (2) and nudiposide (3), and a sterol, ergosta-4,6,8(14),22-tetraen-3-one (4), with stigmasterol, and oleic and linoleic acids, have been isolated from an MeOH extract of the dried bark of Aphanamixis polystachya. The structures of the isolated compounds were elucidated by analysis of 1D and 2D NMR and mass spectroscopic data. The compounds did not have growth inhibitory activity against HeLa cells.     

<Emphasis Type="Italic">In Vitro</Emphasis> hepatoprotective compounds from <Emphasis Type="Italic">Suaeda glauca</Emphasis>

Bioassay-guided fractionation of the MeOH extract of Suaeda glauca yielded four phenolic compounds, methyl 3,5-di-O-caffeoyl quinate (1) and 3,5-di-O-caffeoyl quinic acid (2), isorhamnetin 3-O-beta-D-galactoside (3), and quercetin 3-O-beta-D-galactoside (4). Compounds 1 and 2 were hepatoprotective against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells with the EC(50) values of 72.7+/-6.2 and 117.2+/-10.5 microM, respectively. Silybin as a positive control showed an EC(50) value of 82.4+/-4.1 microM.     

Antioxidative constituents from<Emphasis Type="Italic">Buddleia officinalis</Emphasis>

Four flavonoids (1-4), a phenylethyl glycoside (5), and a phenylpropanoid glycoside (6) were isolated from the flowers of Buddleia officinalis (Loganiaceae). Their structures were determined by chemical and spectral analysis. Among the isolated compounds, luteolin (1) and acteoside (6) exhibited the most potent antioxidative activity on the NBT superoxide scavenging assay. In addition, compounds 1-6 revealed weak antifungal activity, and no hemolytic activity.     

New Aconitine-Type C<Subscript>19</Subscript>-Diterpenoid Alkaloids from<Emphasis Type="Italic">Aconitum hemsleyanium</Emphasis> var.<Emphasis Type="Italic">circinacum</Emphasis>

Two new aconitine-type C19-diterpenoid alkaloids, hemsleyanines C (1) and D (2), were isolated from the roots of Aconitum hemsleyanium var. circinacum, their structures were determined by the chemical evidence and spectral analyses.     

Two new antibacterial norabietane diterpenoids from cyanobacteria, <Emphasis Type="Italic">Microcoleous </Emphasis><Emphasis Type="Italic">lacustris</Emphasis>

Two abietane diterpenes were isolated from cyanobacteria Microcoleous lacustris, 20-nor-3α-acetoxyabieta-5,7,9,11,13-pentaene and 20-nor-3α-acetoxy-12-hydroxy-abieta-5,7,9,11,13-pentaene. These compounds were assayed against Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhi, Vibrio cholerae, Bacillus subtilis, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae. Both compounds showed activity against S. aureus, S. epidermidis, S. typhi, and V. cholerae, but not against the other bacteria.     

Lignan constituents from <Emphasis Type="Italic">Chloranthus japonicus</Emphasis> Sieb.

A new coumarinolignan glucoside named yinxiancaoside C, along with five known benzofuran lignans, have been isolated from the whole plant of Chloranthus japonicus Sieb. The structures of compounds 1–6 were elucidated by chemical and spectroscopic methods including 1D-NMR, 2D-NMR, ESI-MS and HR-ESI-MS. Five known benzofuran lignans were firstly discovered in the Chloranthaceae. In addition, the cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2), ovarian carcinoma (OV420), and breast cancer (MCF-7) cells was investigated by MTT method.