Tomatidine, a tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in apoE-deficient mice by inhibiting acyl-CoA:cholesterol acyl-transferase (ACAT)

It was previously revealed that esculeoside A, a new glycoalkaloid, and esculeogenin A, a new aglycon of esculeoside A, contained in ripe tomato ameliorate atherosclerosis in apoE-deficent mice. This study examined whether tomatidine, the aglycone of tomatine, which is a major tomato glycoalkaloid, also shows similar inhibitory effects on cholesterol ester (CE) accumulation in human monocyte-derived macrophages (HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly inhibited the CE accumulation induced by acetylated LDL in HMDM in a dose-dependent manner. Tomatidine also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1 and ACAT-2 activities. Furthermore, the oral administration of tomatidine to apoE-deficient mice significantly reduced levels of serum cholesterol, LDL-cholesterol, and areas of atherosclerotic lesions. The study provides the first evidence that tomatidine significantly suppresses the activity of ACAT and leads to reduction of atherogenesis.     

Antimutagenic activity of polymethoxyflavonoids from Citrus aurantium

The methanol extract from Citrus aurantium showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract from C. aurantium was successively re-extracted with hexane, dichloromethane, butanol, and water. A dichloromethane fraction showed a suppressive effect. The suppressive compounds in the dichloromethane fraction were isolated by SiO(2) column chromatography and identified as tetra-O-methylscutellarein (1), sinensetin (2), and nobiletin (3) by EI-MS and (1)H- and (13)C NMR spectroscopy. These compounds suppressed the furylfuramide-induced SOS response in the umu test. Gene expression was suppressed 67%, 45%, and 25% at a concentration of 0.6 micromol/mL, respectively. The ID(50) value (50% inhibition dose) of compound 1 was 0. 19 micromol/mL. These compounds were assayed with other mutagens, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes, activated Trp-P-1, and UV irradiation. These compounds showed of all mutagen-induced SOS response in the umu test. In addition, compounds 1-3 exhibited antimutagenic activity in the S. typhimurium TA100 Ames test.     

Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis

Plants from Iryanthera genus have been traditionally used as food supplements by South American Indians. The MeOH extract of leaves of Iryanthera juruensis, one of the plants endemic to the Amazon region and consumed in Brazil, and the hexane extract from its seeds inhibited lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2)) enzymes in in vitro assays. Further analyses of these extracts yielded 5-deoxyflavones (1-5) from the leaf extract and sargachromenol (6), sargaquinoic acid (7), a novel juruenolic acid (8), omega-arylalkanoic acids (9a-c), and the lignan guaiacin (10) from the seed extract. Compounds 3-5 inhibited LPO by 86%, 77%, and 88% at 10 ppm, respectively, and compounds 6 and 9a-c showed inhibition at 76% and 78% at 100 ppm, respectively. However, compounds 7 and 8 were inactive and lignan 10 exhibited LPO inhibitory activity by 99% at 100 ppm compared to commercial antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. The flavones 1-5 also inhibited COX-1 and -2 enzymes by 50-65% at 100 ppm. Compound 6 showed high but nonselective inhibition of COX-1 and COX-2 enzymes, when compared to aspirin and Celebrex, a nonsteroidal anti-inflammatory drug (NSAID). Compounds 7 and 10 inhibited COX-1 by 60% and 65% and COX-2 by 37% and 18%, respectively, whereas compounds 8 and 9a-c showed little or no activity against these enzymes.     

Chemical constituents of Morinda citrifolia fruits inhibit copper-induced low-density lipoprotein oxidation

The oxidative modification of low-density lipoprotein (LDL) plays an important role in the genesis of arteriosclerosis. The present study focused on the effects of the fruits of Morinda citrifolia on preventing arteriosclerosis. The MeOH extract and CHCl(3)-, EtOAc-, n-BuOH-, and H(2)O-soluble phases derived from the fruits of M. citrifolia were evaluated for their inhibitory activity on copper-induced LDL oxidation by the thiobarbituric acid-reactive substances (TBARS) method. The MeOH extract and EtOAc-soluble phase showed 88 and 96% inhibition, respectively. Six lignans were isolated by repeated column chromatography from the EtOAc-soluble phase. These compounds were determined by spectroscopic analysis to be 3,3'-bisdemethylpinoresinol (1), americanol A (2), americanin A (3), americanoic acid A (4), morindolin (5), and isoprincepin (6), of which 4 and 5 are novel compounds. These compounds inhibited copper-induced LDL oxidation in a dose-dependent manner. 1, 2, 5, and 6 exhibited remarkably strong activities, which were the same or better than that of the known antioxidant 2,6-di-tert-butyl-p-cresol. The IC(50) values for 1, 2, 5, and 6 were 1.057, 2.447, 2.020, and 1.362 microM, respectively. The activity of these compounds is mainly due to their number of phenolic hydroxyl groups.     

Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa

The bioassay-guided isolation and purification of the hexane extract of the cultured mycelia of Grifola frondosa led to the characterization of a fatty acid fraction and three compounds, ergosterol (1), ergostra-4,6,8(14),22-tetraen-3-one (2), and 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (3). The composition of fatty acid fraction was confirmed as palmitic, oleic, and linoleic acids by GC-MS and by comparison with the retention values of authentic samples. The structures of compounds 1-3 were established by spectroscopic methods. The fatty acid fraction and compounds 1-3 showed cyclooxygenase (COX) enzyme inhibitory and antioxidant activities. The inhibition of COX-1 enzyme by the fatty acid fraction and compounds 1-3 at 250 microg/mL were 98, 37, 55, and 67%, respectively. Similarly, COX-2 enzyme activity was reduced by fatty acid fraction and compounds 1-3 at 250 microg/mL by 99, 37, 70, and 4%, respectively. The inhibitions of liposome peroxidation by the fatty acid fraction and compounds 1 and 2 at 100 microg/mL were 79, 48, and 42%, respectively. This is the first report of compounds 2 and 3 from the cultured mycelia of G. frondosa. The COX inhibitory activities of compounds 1-3 are reported here for the first time.     

Red and white wines inhibit cholesterol oxidation induced by free radicals

The capabilities of two red (RW) and two white wines (WW) in inhibiting cholesterol oxidation were evaluated using a cholesterol emulsion (CE) system. Each RW or WW was mixed with CE at different (v/v) ratios. Cholesterol oxidation was accelerated by a free radical generator, 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), at 37 °C. The major oxidation product, 7-ketocholesterol, was monitored to determine cholesterol stability in the CE system. At a ratio of 1:250 (RW/CE), 7-ketocholesterol production was not detected during 72 h of oxidation. At a 1:1000 ratio, the inhibition rate of each RW was maintained at 100% at 24 h but decreased afterward. Both WWs had 100% inhibition rate within 48 h at a ratio of 1:10. Also, the capabilities of catechin and resveratrol solutions (1 mg/mL) in inhibiting cholesterol oxidation were studied. Each of the wine polyphenolics showed a 100% of 7-ketocholesterol inhibition rate in 24 h at a ratio of 1:500 (solution/CE). However, the inhibition rate of resveratrol was lower than that of catechin at 48 or 72 h. The results demonstrated that red wine possesses great anti-cholesterol-oxidation capability, which may contribute to health benefits in preventing cardiovascular diseases. Catechin may play a more important role than resveratrol in inhibiting cholesterol oxidation.     

Germination and growth inhibitors from wheat (Triticum aestivum L.) husks

On the basis of our findings that the germination of intact wheat seeds (with husks) belonging to dormancy varieties was restrained as compared with that of the dehusked seeds (grains), the germination inhibitors in the husks were explored. The water-soluble extracts from the husks were separated by the aid of inhibition assay experiments, resulting in the characterization of 2-phenylethyl alcohol 1, 4-vinylphenol 2 and its 2-methoxy derivative 3, and dihydroactinidiolide 4, all of which showed clear inhibition of germination at 500 ppm in aqueous solution. The related compounds 1-phenylethyl alcohol 5 and tetrahydroactinidiolide 6 were as active as 1 and 4, while no noticeable difference in activity was detected among both enantiomers and the DL-form of compounds 4-6. Clear synergistic relations were observed between 4 and 1 and also 4 and 3. Since the present inhibitors have been isolated from various kinds of seed plants, they may be responsible for the general germination inhibition in the seed plants.     

Phytotoxicity of lignanamides isolated from the seeds of Hyoscyamus niger

Bioassay-guided fractionation of phytotoxic extracts prepared from the seeds of Hyoscyamus niger led to the isolation of three new lignanamides (1-3), along with six known lignanamides (4-9). The structures of the new compounds were determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, and high-resolution electrospray ionization mass spectrometry. The bioactivity analysis of the isolated compounds showed that compound 3 exhibited significant inhibition on the germination and radical elongation of Allium fistulosum at 10(-4) M concentration.     

Prenylated flavanones isolated from flowers of Azadirachta indica (the neem tree) as antimutagenic constituents against heterocyclic amines

Four prenylated flavanones were isolated from the methanol extract of the flowers of Azadirachta indica (the neem tree) as potent antimutagens against Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) in the Salmonella typhimurium TA98 assay by activity-guided fractionation. Spectroscopic properties revealed that those compounds were 5,7,4'-trihydroxy-8-prenylflavanone (1), 5,4'-dihydroxy-7-methoxy-8-prenylflavanone (2), 5,7,4'-trihydroxy-3',8-diprenylflavanone (3), and 5,7,4'-trihydroxy-3',5'-diprenylflavanone (4). All isolated compounds were found for the first time in this plant. The antimutagenic IC(50) values of compounds 1-4 were 2.7 +/- 0.1, 3.7 +/- 0.1, 11.1 +/- 0.1, and 18.6 +/- 0.1 microM in the preincubation mixture, respectively. These compounds also similarly inhibited the mutagenicity of Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). All of the compounds 1-4 strongly inhibited ethoxyresorufin O-dealkylation activity of cytochrome P450 1A isoforms, which catalyze N-hydroxylation of heterocyclic amines. However, compounds 1-4 did not show significant inhibition against the direct-acting mutagen NaN(3). Thus, the antimutagenic effect of compounds 1-4 would be mainly based on the inhibition of the enzymatic activation of heterocyclic amines.     

蛋黄油的提取及其氧化产物挥发性成分分析

为提高淘汰蛋鸡副产物——卵泡的利用率,本研究以鸡卵泡为试验原料,经提取卵磷脂、脱去胆固醇后,将其卵泡残渣以溶剂萃取法提取出蛋黄油,通过单因素试验和正交试验研究了提取温度、提取时间、料液比和乙醇浓度对蛋黄油提取的影响。之后将提取的蛋黄油进行氧化调控,采用气相离子迁移色谱(GC-IMS)进行测定与分析。正交试验结果表明,鸡卵泡中蛋黄油提取的最佳工艺条件:提取温度80℃,提取时间55 min,料液比1∶10,乙醇浓度95%。氧化蛋黄油中含有多种挥发性物质,包括4种醇类、3种醛类、2种酯类、2种酮类、1种呋喃,其中3-甲基丁醛是氧化蛋黄油的特征风味物质。本研究结果为开发利用蛋鸡副产物,提高产品附加值提供了新思路。     

Isolation,structural elucidation,and inhibitory effects of terpenoid and lipid constituents from sunflower pollen on Epstein-Barr virus early antigen induced by tumor promoter,TPA

Eight fatty acid esters of triterpene alcohols (1-8), four free triterpene alcohols (9, 12, 17, and 18), four diterpene acids (19-22), two tocopherol-related compounds (23 and 24), four estolides (25-28), three syn-alkane-4,6-diols (29-31), one 1,3-dioxoalkanoic acid (32), and one aliphatic ketone (33), along with the mixture of free fatty acids, were isolated from the diethyl ether extract of the pollen grains of sunflower (Helianthus annuus). Among these compounds, 14 (2-8, 12, 23, 25-28, and 33) were new naturally occurring compounds, and their structures were determined on the basis of spectroscopic methods. Twenty-four terpenoids and lipids (1-4, 6-9, 12, and 19-33) and six free triterpene triols (10, 11, and 13-16), derived from their fatty acid esters (2, 3, and 5-8) by alkaline hydrolysis, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells, which is known to be a primary screening test for antitumor promoters. Among the 30 compounds tested, 21 compounds possessing a di- or a polycyclic ring system in the molecule (1-4, 6-16, and 19-24) showed potent inhibitory effects on EBV-EA induction (91-100% inhibition at 1 x 10(3) mol ratio/TPA).     

Inhibition of xanthine oxidase and suppression of intracellular reactive oxygen species in HL-60 cells by theaflavin-3,3'-digallate, (-)-epigallocatechin-3-gallate, and propyl gallate

The inhibitory effects of five tea polyphenols, namely theaflavin (TF1), theaflavin-3-gallate (TF2), theaflavin-3,3'-digallate (TF3), (-)-epigallocatechin-3-gallate (EGCG), and gallic acid, and propyl gallate (PG) on xanthine oxidase (XO) were investigated. These six antioxidant compounds reduce oxidative stress. Theaflavins and EGCG inhibit XO to produce uric acid and also act as scanvengers of superoxide. TF3 acts as a competitive inhibitor and is the most potent inhibitor of XO among these compounds. Tea polyphenols and PG all have potent inhibitory effects (>50%) on PMA-stimulated superoxide production at 20 approximately 50 microM in HL-60 cells. Gallic acid (GA) showed no inhibition under the same conditions. At 10 microM, only EGCG, TF3, and PG showed significant inhibition with potency of PG > EGCG > TF3. The superoxide scavenging abilities of these six compunds are as follows: EGCG > TF2 > TF1 > GA > TF3 > PG. PG was the most potent inhibitor of PMA-stimulated H(2)O(2) production in HL-60 cells. The order of H(2)O(2) scavenging ability was TF2 > TF3 > TF1 > EGCG > PG > GA. Therefore, the antioxidative activity of tea polyphenols and PG is due not only to their ability to scavenge superoxides but also to their ability to block XO and related oxidative signal transducers.     

Influenza virus neuraminidase inhibitory activity of phlorotannins from the edible brown alga Ecklonia cava

Influenza A virus infections continue to pose a major threat to humans and several animal species. Neuraminidase (NA) is one of the most promising targets for the development of drugs against influenza viruses because of its critical role in the viral life cycle. During the course of a search for NA inhibitors from edible natural sources, we found that the ethyl acetate layer of ethanol extracts of Ecklonia cava showed extremely high NA-inhibitory activity (72.1% inhibition at 30 μg/mL). Bioactivity-guided fractionation of the ethyl acetate layer yielded five phlorotannins, identified as phloroglucinol (1), eckol (2), 7-phloroeckol (3), phlorofucofuroeckol (4), and dieckol (5). The inhibitory activities of these compounds (1-5) against NAs from group-1 (A/Bervig_Mission/1/18 [H1N1], A/PR/8/34 [H1N1]) and group-2 (A/Hong Kong/8/68 [H3N2], A/Chicken/Korea/MS96/96 [H9N2]) influenza A were evaluated to determine potencies and kinetic behavior. Analyses using various in vitro influenza A virus NA assays showed that all five phlorotannin derivatives were selective NA inhibitors. Of the phlorotannins, phlorofucofuroeckol (4) exhibited the most potent inhibitory activities toward group-1 NAs (IC?? values, 4.5 and 14.7 μM), whereas dieckol (5) potently inhibited group-2 NAs. Kinetic analyses indicated that compounds 1-5 were all noncompetitive. Notably, these noncompetitive inhibitors synergized with oseltamivir to enhance the NA-inhibitory effects of oseltamivir.     

Biologically active carbazole alkaloids from Murraya koenigii

The bioassay guided fractionation of the acetone extract of the fresh leaves of Murraya koenigii resulted in the isolation of three bioactive carbazole alkaloids, mahanimbine (1), murrayanol (2), and mahanine (3), as confirmed from their (1)H and (13)C NMR spectral data. Compound 2 showed an IC(50) of 109 microg/mL against hPGHS-1 and an IC(50) of 218 microg/mL against hPGHS-2 in antiinflammatory assays, while compound 1 displayed antioxidant activity at 33.1 microg/mL. All three compounds were mosquitocidal and antimicrobial and exhibited topoisomerase I and II inhibition activities.     

Phytoene desaturase inhibition by O-(2-phenoxy)ethyl-N-aralkylcarbamates

O-[1-Ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate exhibits a marked inhibition of carotenoid biosynthesis. Forty-one analogues were synthesized and assayed for plant-type phytoene desaturase (PDS) and zeta-carotene desaturase (ZDS) inhibition in a cell-free system using recombinant enzymes obtained from Escherichia coli transformants. The target enzyme of all carbamates synthesized in this study is PDS and not ZDS; no inhibition of ZDS was observed using a 10(-4) M inhibitor concentration. Four compounds, O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-phenylethyl)carbamate (23), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (25), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (26), and O-[1-methyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate (30), were the most potent PDS inhibitors. Their pI(50) values, the negative logarithms of the molar concentration that produces a 50% inhibition, were 7.5, representing the same inhibitory activity as norflurazon. With respect to a structure-activity relationship the oxygen atom of the phenoxy group and a carbamate structure in O-(1-ethyl-2-phenoxy)ethyl-N-aralkylcarbamates studied were found to be essential for strong PDS inhibitors. Also, introduction of an ethyl group at the alpha-position of the ethylene bridge between the phenoxy group and the carbamate was important for a strong PDS inhibitor. Substituents at the 2- and/or 3-position of the phenoxybenzene ring were found to be favorable to a strong PDS inhibition of the analogues.     

Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis)

One known and two novel antioxidant compounds have been isolated from bamboo (Phyllostachys edulis). The butanol-soluble extract of the bamboo leaves was found to have a significant antioxidant activity, as measured by scavenging the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and the superoxide anion radical (O(2)(-)) in the xanthine/xanthine oxidase assay system. Antioxidant activity-directed fractionation of the extract led to the isolation and characterization of three structural isomeric chlorogenic acid derivatives: 3-O-(3'-methylcaffeoyl)quinic acid (1), 5-O-caffeoyl-4-methylquinic acid (2), and 3-O-caffeoyl-1-methylquinic acid (3). Compounds 2 and 3 were isolated and characterized for the first time from the natural products. In the DPPH scavenging assay as well as in the iron-induced rat microsomal lipid peroxidation system, compounds 2 (IC(50) = 8.8 and 19.2 microM) and 3 (IC(50) = 6.9 and 14.6 microM) showed approximately 2-4 times higher antioxidant activity than did chlorogenic acid (IC(50) = 12.3 and 28.3 microM) and other related hydroxycinnamates such as caffeic acid (IC(50) =13.7 and 25.5 microM) and ferulic acid (IC(50) = 36.5 and 56.9 microM). Among the three compounds, compound 1 yielded the weakest antioxidant activity, and the DPPH scavenging and lipid peroxidation inhibitory activity (IC(50) = 16.0 and 29.8 microM) was lower than those of chlorogenic and caffeic acids. All three compounds exhibited both superoxide scavenging activities and inhibitory effects on xanthine oxidase. Their superoxide anion (O(2)(-)) scavenging activities (IC(50) = 1, 4.3 microM; 2, 2.8 microM; and 3, 1.2 microM) were markedly stronger than those of ascorbic acid (IC(50) = 56.0 microM), alpha-tocopherol (IC(50) > 100 microM), and other test compounds, although their inhibition effects on xanthine oxidase may contribute to the potent scavenging activity. alpha-Tocopherol exerted a significant inhibitory effect (65.5% of the control) on superoxide generation in 12-O-tetradecanoylphorbol-13-acetate-induced human promyelocytic leukemia HL-60 cells, and compound 3 showed moderate activity (36.0%). On the other hand, other compounds including 1, 2, chlorogenic acid, and other antioxidants were weakly active (24.8-10.1%) in the suppression of superoxide generation.     

Comparison of the essential oils of Glehnia littoralis from Northern and Southern Japan.

The essential oils from aerial and root parts of Glehnia littoralis were investigated by GC and GC-MS, and 125 compounds were identified. Plants were obtained from Northern and Southern Japan, and samples from the same locations were cultivated either exposed or unexposed to sunlight. The main constituents of the essential oils were found to be alpha-pinene (0.03-13.40%), limonene (0.15-10.71%), beta-phellandrene (0.03-22.93%), germacrene B (0.27-8.33%), spathulenol (0.24-6.50%), beta-oplopenone (0.06-6.47%), panaxynol (0.38-24.58%), propyl octanoate (3.44-27.85%), hexadecanoic acid (0.45-27.80%), and linoleic acid (0.16-17.56%). Terpenoid compounds were found in higher concentrations in the Northern type oils than in the Southern types, whereas the concentration of polyacetylenic compounds was higher in one of the Southern samples, except from the aerial parts of those cultivated exposed. Consequently, the constitution of the essential oils from G. littoralis could be separated into Northern and Southern types.     

Antifungal synergistic effect of scopoletin, a hydroxycoumarin isolated from Melia azedarach L. fruits

In the continuous search for antifungal compounds from plants, the hydroxycoumarin scopoletin (1) was isolated from seed kernels of Melia azedarach L. from which three other compounds, vanillin (2), 4-hydroxy-3-methoxycinnamaldehyde (3), and (+/-) pinoresinol (4), have also been isolated. Guided fractionation through autobiography on TLC using Fusarium verticillioides (Saccardo) Nirenberg as test organism led to the isolation of 1, which exhibited a minimum inhibitory concentration (MIC) of 1.50 mg/mL in the microbroth dilution method. Despite its own weak activity, when the coumarin was combined with the above-mentioned compounds, a strong enhancement of the antifungal effect was observed, even showing a complete inhibition in the growth of the pathogen when 1 was added at a concentration of up to 5% of its MIC value. The same level of effectiveness was observed when the synthetic antifungal agents Mancozeb and Carboxin were each combined with compounds 1-4, in which cases it became possible to decrease the effective concentrations of these commercial compounds by up to 2.5 and 3%, respectively.     

Synthesis and herbicidal activity of 2alpha, 4alpha-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one derivatives.

The catalytic oxidation of 2alpha,4alpha-dimethyl-8-oxabicyclo[3.2. 1]oct-6-en-3-one with osmium tetraoxide and excess hydrogen peroxide resulted in the formation of 2alpha,4alpha-dimethyl-6, 7-exo-isopropylidenedioxy-8-oxabicyclo[3.2.1]octan-3-one (2), with 91% yield. Addition of aryllithium reagents to this compound resulted in the formation of the aromatic alcohols (6a-h) with 48-76% yield. These alcohols were treated with thionyl chloride in pyridine, and the corresponding alkenes (7a-h) were obtained with 46-80% yield. The effect of compounds 6a-h and 7a-h on the root growth of Sorghum bicolor was evaluated at a concentration of 6.6 microg g(-)(1). The alcohols 6a-h caused an inhibitory effect (8-100%) on the S. bicolor radicle growth. The three most active compounds were 6e (aryl = p-methylphenyl), 6g (aryl = p-chlorophenyl), and 6h (aryl = p-fluorophenyl) and caused 100% inhibition. The effect of alkenes 7a-h was less pronounced and varied from 15% to 46% inhibition. Another experiment was carried out in a greenhouse to evaluate the effect of alcohols 6e, 6g, and 6h, at a 6.6 microg g(-)(1) dose, against Cucumis sativus, S. bicolor and the weeds Bidens pilosa, Desmodiumtortuosum, and Pennisetum setosum. All three compounds showed an inhibitory effect on the development of the aerial parts (26-73%) and roots (13-79%) of the weeds and crops.     

Antimutagenic activity of flavonoids from Pogostemon cablin

A methanol extract from Pogostemon cablin showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract was re-extracted with hexane, dichloromethane, butanol, and water. A dichloromethane fraction showed a suppressive effect. Suppressive compounds against furylfuramide in the dichloromethane fraction were isolated by SiO(2) column chromatography and identified as 7,4'-di-O-methyleriodictyol (1), 7, 3',4'-tri-O-methyleriodictyol (2), and 3,7,4'-tri-O-methylkaempferol (3). In addition, three flavonoids, ombuine (4), pachypodol (5), and kumatakenin (6), were isolated and identified from the dichrolomethane fraction. Compounds 1 and 3 suppressed >50% of the SOS-inducing activity at <0.6 micromol/mL, and the ID(50) values of both compounds were 0.25 micromol/mL. Compound 2 showed a weakly suppressive effect (17%) at a concentration of 0.6 micromol/mL, and compounds 4-6 did not. These compounds were also assayed with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes. Compounds 3-6 suppressed >80% of the SOS-inducing activity of Trp-P-1 at <0.06 micromol/mL, and compounds 1 and 2 suppressed 87 and 63% at a concentration of 0.3 micromol/mL. In addition, these compounds were assayed with activated Trp-P-1, and the suppressed effects of these compounds were further decreased when compared to Trp-P-1. The antimutagenic activities of these compounds against furylfuramide, Trp-P-1, and activated Trp-P-1 were assayed by the Ames test using S. typhimurium TA100.