Comparison of larvicidal, adulticidal and acaricidal activity of two geometrical butylidenephthalide isomers.
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Insecticidal and acaricidal activities of two geometrical isomers, (E)- and (Z)-butylidenephthalide isolated from Angelica acutiloba, against larvae and adults of fruit fly (Drosophila melanogaster), cat fleas (Ctenocephalides felis) and house dust mites (Dermatophagoides farinae and Tyrophagus putrescentiae) were investigated and compared with that of positive controls. (E)- and (Z)-Butylidenephthalide exhibited 50% lethal concentration (LC50) values of 2.07 and 0.94 micromol/ml of diet concentration against larvae of D. melanogaster, respectively. This indicated that two isomers of butylidenephthalide have geometrical stereoselectivity for larvicidal effect. Even though both (E)- and (Z)-butylidenephthalide also showed potent adulticidal and acaricidal activity against adults of D. melanogaster and two mites, there was no significant difference between two isomers. Insecticidal activity of both (E)- and (Z)-butylidenephthalide toward adults of C. felis was not detected even at the maximum concentration of 200 microg/cm2. (+info)
Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis.
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Serotonin receptor (5-HT(7)) binding assay-directed fractionation of a methanol extract of the dried roots of Angelica sinensis led to the isolation and identification of 21 compounds including a new phenolic ester, angeliferulate (1), and three new phthalides, 10-angeloylbutylphthalide (2), sinaspirolide (3), and ansaspirolide (4), along with 17 known compounds, p-hydroxyphenethyl trans-ferulate (5), Z-ligustilide (6), Z-butylidenephthalide (7), senkyunolide I (8), Z-6-hydroxy-7-methoxydihydroligustilide (9), N-butylbenzenesulfonamide (10), 11(S),16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1-yl acetate (11), (3R,8S)-falcarindiol (12), heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diol (13), oplopandiol (14), 8-hydroxy-1-methoxy-, Z-9-heptadecene-4,6-diyn-3-one (15), imperatorin, ferulic acid, vanillin, stigmasterol, sucrose, and 1,3-dilinolenin. This is the first report of a sulfonamide (10) identified from a higher plant source, although its presence needs further investigation. Biosynthetic pathways for dimeric phthalides 3 and 4 are proposed. Compounds 5, 7, 11, 12, 15, and imperatorin exhibited affinity toward 5-HT(7) receptors in a competitive binding assay. (+info)
Antioxidant and antigenotoxic activities of Angelica keiskei, Oenanthe javanica and Brassica oleracea in the Salmonella mutagenicity assay and in HCT116 human colon cancer cells.
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Epidemiological studies indicate that consumption of green-yellow vegetables rich in chlorophyll, vitamin C, vitamin E, and carotenoids reduce the risk of cancer. We sought to examine the antigenotoxic and antioxidant properties of chlorophyll-rich methanol extracts of Angelica keiskei, Oenanthe javanica, and Brassica oleracea (kale). In the Salmonella mutagenicity assay, A. keiskei caused dose-dependent inhibition against three heterocyclic amine mutagens in the presence of S9, O. javanica was antimutagenic only at the highest concentration in the assay (2 mg/plate), and B. oleracea showed no consistent inhibitory activity at non-toxic levels. None of the extracts were effective against three direct-acting mutagens in the absence of S9. Extracts of A. keiskei and, to a lesser extent O. javanica, inhibited two of the major enzymes that play a role in the metabolic activation of heterocyclic amines, based on ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase assays in vitro. All three plant extracts were highly effective in assays which measured ferric reducing/antioxidant power, oxygen radical absorbance capacity, and Fe2+/H2O2-mediated DNA nicking. Finally, using the 'comet' assay, all three plant extracts protected against H2O2-induced genotoxic damage in human HCT116 colon cancer cells. These findings provide support for the antigenotoxic and antioxidant properties of chlorophyll-rich extracts of A. keiskei, O. javanica, and B. oleracea, through mechanisms that include inhibition of carcinogen activation and scavenging of reactive oxygen species. (+info)
A novel class of pyranocoumarin anti-androgen receptor signaling compounds.
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Androgen and the androgen receptor (AR)-mediated signaling are crucial for prostate cancer development. Novel agents that can inhibit AR signaling in ligand-dependent and ligand-independent manners are desirable for the chemoprevention of prostate carcinogenesis and for the treatment of advanced prostate cancer. We have shown recently that the pyranocoumarin compound decursin from the herb Angelica gigas possesses potent anti-AR activities distinct from the anti-androgen bicalutamide. Here, we compared the anti-AR activities and the cell cycle arrest and apoptotic effects of decursin and two natural analogues in the androgen-dependent LNCaP human prostate cancer cell culture model to identify structure-activity relationships and mechanisms. Decursin and its isomer decursinol angelate decreased prostate-specific antigen expression with IC(50) of approximately 1 mumol/L. Both inhibited the androgen-stimulated AR nuclear translocation and transactivation, decreased AR protein abundance through proteasomal degradation, and induced G(0/1) arrest and morphologic differentiation. They also induced caspase-mediated apoptosis and reactive oxygen species at higher concentrations. Furthermore, they lacked the agonist activity of bicalutamide in the absence of androgen and were more potent than bicalutamide for suppressing androgen-stimulated cell growth. Decursinol, which does not contain a side chain, lacked the reactive oxygen species induction and apoptotic activities and exerted paradoxically an inhibitory and a stimulatory effect on AR signaling and cell growth. In conclusion, decursin and decursinol angelate are members of a novel class of nonsteroidal compounds that exert a long-lasting inhibition of both ligand-dependent and ligand-independent AR signaling. The side chain is critical for sustaining the anti-AR activities and the growth arrest and apoptotic effects. (+info)
Effects of dietary Angelica keiskei on serum and liver lipid profiles, and body fat accumulations in rats.
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Angelica keiskei (Ashitaba) is a perennial plant belonging to the Umbelliferae family. Recently, much attention has been focused on Ashitaba products as a so-called health food for the breakdown of cellulite among various physiological benefits of Ashitaba. The current study was carried out to investigate the physiological efficacy of dietary Ashitaba on serum and liver lipid profiles and body fat accumulation in rats. Rats were fed a high-fat diet with various amounts of Ashitaba for 28 d. Perirenal adipose tissue weights of rats fed the x 10 (170 mg/100 g BW) Ashitaba diet were significantly higher (p < 0.05) than those of the control group. Serum triacylglycerol concentrations of rats fed the x 100 (1,700 mg/100 g BW) Ashitaba diet were significantly higher (p < 0.05) than those of the x 1 (17 mg/100 g BW) group. Fecal weights and bile acid excretions of rats fed the x 10 or x 100 Ashitaba diet were significantly higher (p < 0.05) than those of the control group. However, there were no significant differences in the body weight gain, epididymal adipose tissue weight, serum cholesterol or liver lipid concentrations or other biochemical profiles in the serum. Furthermore, even the excessive ingestion of Ashitaba had no significant pathological impact on the liver or kidney. These results indicate that the large intake of Ashitaba products may supply dietary fiber and thus improve gastrointestinal condition through the increased excretion of feces containing high level of bile acids, although even excessive intake of Ashitaba for a short period of 28 d did not show any impact on the decrease in body fat or modification of lipid profiles in this study. (+info)
Mechanism-based inactivation of cytochrome P450 2A6 by decursinol angelate isolated from Angelica Gigas.
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The inhibition of CYP2A6 by decursinol angelate, a pyranocoumarin isolated from Angelica gigas roots, was examined in human liver microsomes and recombinant CYP2A6. Decursinol angelate moderately inhibited coumarin 7-hydroxylation, but a 20-min preincubation with microsomes and NADPH significantly increased its inhibitory effect (IC(50); >20 versus 4.4 microM). A similar inhibition pattern was observed in nicotine C oxidation, which is also one of the prototype reactions of CYP2A6. Inactivation by decursinol angelate was selective for CYP2A6 and characterized by K(I) values of 0.99 and 2.42 microM and the k(inact) values of 0.136 and 0.053 min(-1) in microsomes and recombinant CYP2A6, respectively. This inactivation was not protected or restored by nucleophiles, reactive oxygen scavengers, or extensive dialysis but was inhibited by the addition of a competitive CYP2A6 inhibitor, pilocarpine. Furthermore, incubation of CYP2A6 with decursinol angelate in the presence of NADPH resulted in a loss of the spectral CYP2A6 content. An in vitro metabolism study revealed that CYP2A6 oxidized decursinol angelate to the dihydrodiol metabolite, presumably via an epoxide intermediate that might be responsible for the inactivation of CYP2A6. These results collectively demonstrated that decursinol angelate inactivated CYP2A6 in a mechanism-based mode. (+info)
Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of beta-catenin.
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Alterations in the Wnt/beta-catenin pathway are associated with the development and progression of human prostate cancer. Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, inhibits the growth of androgen-independent human prostate cancer cells, but little is known about its mechanism of action. Using a cell-based screen, we found that decursin attenuates the Wnt/beta-catenin pathway. Decursin antagonized beta-catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of beta-catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of beta-catenin and thus inhibited the growth of PC3 prostate cancer cells. In contrast, decursinol, in which the (CH3)2-C=CH-COO- side chain of decursin is replaced with -OH, had no effect on CRT, the level of intracellular beta-catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/beta-catenin pathway. (+info)
Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma.
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Six chalcones from Angelica keiskei KOIDZUMI (Ashitaba in Japanese) and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10(-4) M) exposure. Typical morphologic features of apoptosis, including cell shrinkage, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies, were observed in isobavachalcone-treated cells by Hoechst 33342 staining. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application. These results suggest that isobavachalcone induces apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells. Therefore, isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma. (+info)