Short term treatment with St. John's wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse.

This investigation was designed to determine whether St. John's wort (SJW)(435 mg/kg/d), a readily available antidepressant, or its purported active constituents hypericin (1 mg/kg/d) and hyperforin (10 mg/kg/d) were able to induce various hepatic cytochrome P450 (CYP450) isoforms. SJW, hypericin and hyperforin were administered to male Swiss Webster mice for four consecutive days and hepatic microsomes were prepared on day 5. None of the three treatments resulted in a statistical change in total hepatic CYP450 (SJW treated 0.95 +/- 0.09 nmol/mg vs control 1.09 +/- 0.14 nmol/mg). Furthermore, the catalytic activities of CYP1A2. CYP2E1 and CYP3A were unchanged from control following all three treatments as determined by ethoxyresorufin O-deethylation, p-nitrophenol hydroxylation and erythromycin N-demethylation respectively. Additionally, western immunoblotting demonstrated that there was no significant change in the polypeptide levels of any of the three isoforms. These results indicate that four days of treatment with moderate to high doses of SJW, hyperforin or hypericin fails to induce these CYP450 isoforms in the male Swiss Webster mouse.

St. John's wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse.

This investigation was designed to determine the ability of St. John's wort (SJW), a readily available antidepressant, to induce various hepatic drug metabolizing enzymes. SJW (140 or 280 mg/kg/day) was administered to male Swiss Webster mice for 1, 2, or 3 weeks. Enzymatic activity was analyzed in hepatic microsomes for all of the following drug metabolizing enzymes: CYP3A, CYP1A, CYP2E1, and UDP-glucuronosyltransferase (UDPGT). The catalytic activity of CYP1A was unchanged from control following any dose or duration of SJW, while both CYP3A and CYP2E1 catalytic activities were increased 2-fold by both SJW concentrations but only following 3 weeks of administration. Results from Western immunoblotting studies supported the changes in catalytic activity, as protein levels for CYP2E1 and CYP3A were increased (2.5-fold and 6-fold, respectively) following 3 weeks of SJW administration. Additionally, the catalytic activity of the conjugation enzyme UDPGT was unchanged from control following all SJW treatments. These results indicate that in the mouse moderate doses of SJW cause an increase in the catalytic activity and polypeptide levels of CYP2E1 and CYP3A but only following 21 days of administration, while the catalytic activity of CYP1A and UDPGT activity remain unaffected.

NOESY on neurotoxins: NMR and conformational assignments of picrotoxins.

Nuclear Overhauser effect spectroscopy (NOESY) gave full assignments of the 1H-NMR spectra of the picrotoxane neurotoxins tutin, hyenanchin, picrotoxinin and picrotin, as well as the solution conformations of these compounds, consistent with molecular modelling. Fully assigned 13C-NMR data are reported.

Echinacea standardization: analytical methods for phenolic compounds and typical levels in medicinal species.

A proposed standard extraction and HPLC analysis method has been used to measure typical levels of various phenolic compounds in the medicinally used Echinacea species. Chicoric acid was the main phenolic in E. purpurea roots (mean 2.27% summer, 1.68% autumn) and tops (2.02% summer, 0.52% autumn), and echinacoside was the main phenolic in E. angustifolia (1.04%) and E. pallida roots (0.34%). Caftaric acid was the other main phenolic compound in E. purpurea roots (0.40% summer, 0.35% autumn) and tops (0.82% summer, 0.18% autumn), and cynarin was a characteristic component of E. angustifolia roots (0.12%). Enzymatic browning during extraction could reduce the measured levels of phenolic compounds by >50%. Colorimetric analyses for total phenolics correlated well with the HPLC results for E. purpurea and E. angustifolia, but the colorimetric method gave higher values.

Coriander spice oil: effects of fruit crushing and distillation time on yield and composition.

Crushing intensity and distillation time were evaluated for their effects on the oil yield and composition of steam-distilled essential oil from fruits of Coriandrum sativum var. microcarpum L. A comparison of oils produced by laboratory- and pilot-scale stills showed that the two still types gave comparable yields and oil composition. The laboratory still was then used to compare oil yields and compositions from fruits crushed at three different intensities, at intervals during a distillation period of 60 min. Both crushing intensity and distillation time had significant (P< 0.05) effects on the yield and composition of the oil. The maximum oil yield was less from the light-crushed fruits, but the rate of oil recovery was significantly P < 0.05) higher. From the light-crushed fruits, 95% of the maximum yield was extracted in 22.5 min compared with 32 and 39 min for the standard and heavy-crushed fruits, respectively. The effect of crushing intensity on oil composition was most pronounced on the low-boiling-point a-pinene and on the higher-boiling-point geranyl acetate. Crushing had little effect on linalool content, but distillation time could be manipulated to alter the linalool content of the oil.

The first atisane diterpenoids from a liverwort: polyols from Lepidolaena clavigera.

Two new diterpenoids were isolated from the New Zealand liverwort Lepidolaena clavigera. Spectroscopic studies identified the structures as atisanes 1 and 2, with an unprecedented level of oxygenation. This is the first report of the atisane skeleton from a liverwort. Compound 2 showed cytotoxic and insecticidal activity. [structure: see text]

Chemistry of New Zealand Apiaceae: a rare phenylpropanoid and three new germacrane derivatives from Anisotome lyallii.

A phytochemical investigation of the New Zealand endemic Apiaceae species Anisotome lyallii Hook.f. yielded (+)-alpha-angeloyloxylatifolone (1), 6-O-angeloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (2), 6-O-tigloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (3) and 6-O-tigloyl-8-O-tigloyl-1alpha,6beta,8alpha,11-tetrahydroxygermacra-4E,10-(14)diene (4). The structures were elucidated by HR mass spectrometry and 1D- and 2D-NMR spectroscopy. A chemosystematic survey for compounds 1-3 in other New Zealand Apiaceae by HPLC-MS revealed that 1-3 were confined to A. haastii Cockayne & Laing and A. lyallii, and that some minor compounds in other species of Anisotome were isomers of 2 and 3.

A cytotoxic sesquiterpene caffeate from the liverwort Bazzanianovae-zelandiae.

Extracts of the liverwort Bazzania novae-zelandiae were cytotoxic, with selective activity against human tumor cell lines. Bioactivity-directed isolation work showed that the new compound naviculyl caffeate (1) was the main cytotoxin. This structure was confirmed by synthesis from the co-occurring sesquiterpene naviculol (2).

Alkamide levels in Echinacea purpurea: effects of processing, drying and storage.

The effects of processing, drying, and storage time and temperature on alkamide levels in Echinacea purpurea roots are described. Chopping altered the levels of some alkamides slightly, whereas drying had no effect. Levels of all alkamides fell by over 80% during storage at 24 degrees C for 64 weeks. Alkamide levels also dropped significantly during storage at -18 degrees C.

Essential oils from dalmatian sage (Salvia officinalis l.): variations among individuals, plant parts, seasons, and sites.

The factors affecting oil yield and quality of essential oils from Dalmatian sage (Salvia officinalis L.) are analyzed. Distillations of oils from individual plants and GC analyses revealed the presence of three chemotypes with different proportions of alpha- and beta-thujone (alpha/beta 10:1, 1.5:1, and 1:10). Different accessions could also be classified as having high (39-44%), medium (22-28%), or low (9%) total thujone contents. Flowering parts of S. officinalis had higher oil contents (1.6 versus 1.1%) and beta-pinene levels (27 versus 10%) than leaves and lower thujone levels (16 versus 31%). Major seasonal changes were found in the composition of oil distilled from a flowering type of Dalmatian sage, but oil yields from healthy, established plants did not vary greatly. Total thujone levels were lowest (25%) around flowering in spring and summer, so autumn or winter was the best harvest time to obtain oils with high thujone levels.

11-oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort, Lepidolaena taylorii.

Four new cytotoxic 8,9-secokauranes have been identified from the liverwort Lepidolaena taylorii. The 11-oxygenation found in three of these has not been encountered in the 8,9-secokauranes known from higher plants. NMR studies were combined with molecular modelling to determine the preferred conformations. Six structurally related kauren-15-ones were also found, including three new compounds. Some of these compounds showed differential cytotoxic activity against human tumor cell lines. The probable mode of cytotoxic action was supported by Michael addition of a thiol. Two 8,9-secokauranes were the main cytotoxins in another New Zealand liverwort. L. palpebrifolia.

Antimicrobial and cytotoxic phenolic glycoside esters from the New Zealand tree Toronia toru.

Two new compounds, 4-hydroxyphenyl 6-O-(4-hydroxy-2-methylenebutanoyl)-beta-D-glycopyranoside (1) and 4-hydroxyphenyl 6-O-[(3R)-3,4-dihydroxy-2-methylenebutanoyl]-beta-D-glucopyranosid e (2), have been isolated from foliage of Toronia toru. Compound 2 was the main antimicrobial component (7 mg/g of dry foliage) of the crude extract and also showed significant cytotoxic activity against P-388 leukemia cells.

Alkamide levels in Echinacea purpurea: a rapid analytical method revealing differences among roots, rhizomes, stems, leaves and flowers.

A rapid extraction, clean-up, and RPLC procedure suitable for routine quantitative analyses of alkamide levels in Echinacea purpurea extracts is described. The 13C-NMR spectra of the main diene-diyne alkamides in E. purpurea are reported. Alkamide levels differed significantly among roots, rhizomes, stems, leaves, and flowers of E. purpurea. Roots were distinguished from other plant parts by higher levels of the C12 diene-diyne alkamides, whereas levels of the C12 tetraene alkamides and C11 diene-diynes were highest in vegetative stems. The ratio of the two stereoisomeric C12 tetraene alkamides differed between flowers and all other E. purpurea parts. These results are important for standardisation of medicinal preparations of E. purpurea.

Diplophyllolide: a cytotoxic sesquiterpene lactone from the liverworts Clasmatocolea vermicularis and Chiloscyphus subporosa.

A bioactivity-directed investigation of a New Zealand collection of the liverwort Clasmatocolea vermicularis led to the isolation of the sesquiterpene lactone, diplophyllolide [1], as the major cytotoxic component. The cytotoxic extract of another liverwort, Chiloscyphus subporosa, also contained diplophyllolide.

Isoprenyl phenyl ethers from liverworts of the genus Trichocolea: cytotoxic activity, structural corrections, and synthesis.

The main cytotoxic component in New Zealand collections of the liverwort Trichocolea mollissima was identified as methyl 4-[(5-oxogeranyl)oxy]-3-methoxybenzoate, a structure that has not been reported previously. Two double-bond isomers of this geranyl ether were present at lower levels. Reinvestigation of the benzoates from Japanese collections of Trichocolea tomentella led to the identification of four geranyl ethers (including two of the three compounds identified from T. mollissima), which had previously been assigned incorrect geranyl ester structures. One compound, previously reported as a 3,3-dimethylallyl ester, could not be reisolated from T. tomentella, but was found in a New Zealand collection of Trichocolea lanata. It was shown to be a 3,3-dimethylallyl ether by synthesis from methyl vanillate. Several of these compounds were active in cytotoxic and antifungal assays.

The glycosidic precursor of (Z)-5-ethylidene-2(5H)-furanone in Halocarpus biformis juvenile foliage.

A new glycosidic lactone, (5R,6R)-5-(1-hydroxyethyl)-2(5H)-furanone beta-D-glucopyranoside, has been identified as the principal precursor of (Z)-5-ethylidene-2(5H)-furanone in juvenile foliage of the New Zealand tree Halocarpus biformis. Three related lactone glycosides were isolated in smaller amounts, together with the known phenolic glycosides pyroside, arbutin and picein. The principal lactone glycoside underwent facile elimination of glucose, in neutral or basic conditions, to yield (Z)-5-ethylidene-2(5H)-furanone and its E-isomer. This lactone glycoside was also detected in foliage of H. bidwillii and H. kirkii.

Cytotoxicity and antimicrobial activity of plants from New Zealand's subantarctic islands.

A total of 86 species of bryophytes, lichens and vascular plants were collected from New Zealand's subantarctic Campbell and Auckland Islands, including 18 subantarctic endemic species. Extracts of these species have been screened for antimicrobial activity and toxicity towards a P388 cell line. Of the main taxonomic groups collected, the proportion of extracts with some biological activity was highest for liverworts (25/29), intermediate for flowering plants (17/26) and lowest for mosses and horn worts (4/22). Extracts of six species showed repeatable, high biological activity warranting further investigation. The cytotoxicity of Ranunculus pinguis was due to the presence of ranunculin.

Sesquiterpene/quinol from a New Zealand liverwort, Riccardia crassa.

A new sesquiterpene/quinol, with mild cytotoxic and antibacterial activity, has been isolated from a New Zealand collection of the liverwort Riccardia crassa. The structure of this compound, riccardiphenol C [3], was established by nmr spectroscopy. Closely related compounds previously isolated from a Japanese collection of R. crassa were not detected in this collection.