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We have previously shown that six propolins, A-F, could be isolated from Taiwanese propolis (TP) and that they exerted a broad spectrum of biological activities. Recently, we isolated a seventh compound, propolin G. Its chemical structure has been identified by NMR and fast atom bombardment-mass spectrometry spectra and was found to be identical to a known compound, nymphaeol C. We used high-performance liquid chromatography to determine the relative contents of propolins C, D, F, and G in TP collected in various seasons and regions and found them to be relatively higher in TPs collected from May to July than from September to October. In our present study, we were interested in the various biological activities of TP extract as well as in propolin G as a pure compound. We found that propolin G could efficiently induce apoptosis in brain cancer cell lines (glioma and glioblastoma). The apoptosis might have been through a mitochondrial- and caspase-dependent pathway. This result demonstrated that the TP collection season was more an important factor than the geographical region. Propolis has been suggested to possess a potent antioxidant activity. We further evaluated the antioxidant property of propolin G using DPPH (1,2-diphenyl-2-picryhydrazyl). Our results indicate that propolin G does possess free radical scavenging activity. We also evaluated the neuroprotective action of propolin G, TP, and BP (Brazilian propolis) extracts against oxidative stress in rat primary cortical neurons. Our data demonstrate that propolin G and TP extracts have a marked neuroprotective effect that is greater than BP extract. In conclusion, the isolation and characterization of propolin G from TP have demonstrated for the first time that this compound is a potent inducer of apoptosis in brain cancer cells and that this compound and TP extract exhibit a protective effect against oxidative stress in rat cortical neurons.

Three new (8, 12, 13) and two revised (7, 9) eudesmane alcohols have been identified from the Taiwanese liverwort Lepidoziafauriana, together with a known macrocyclic bisbibenzyl, isoplagiochin D, and other known sesquiterpenoids. Their structures were determined by NMR and X-ray analyses. Three chemo-types of Lepidoziafauriana may be classified according to the skeleton of the major sesquiterpenoids identified in the species.

band Uni-Juni Ean a ( ) a De part ment of Chem is try, Tamkang Uni ver sity, Tamsui, Tai wan 251, R.O.C. b In sti tute of Or ganic Chem is try, Uni ver sity of Ham burg, Mar tin-Luther-King-Platz 6,20146 Ham burg, Ger many A novel lin ear dihydrodichromene de riv a tive, metacalypogin, was iden ti fied from the Tai wan e se liv er wort Metacalypogeia alternifolia. To gether with data from M. cordifolia, the chem i cal marker of the ge nus Metacalypogeia is ob vi ous chroman de riv a tives, which is far dif fer ent from that of Calypogeia, the other ge nus in the same fam ily. In ad di tion, two iso meric diterpenoids of cembrane-type were iden ti fied from the Chi nese liv er wort Chandonanthus hirtellus. The rel a tive stereostructures of the lat ter two iso mers were proved by X-ray crys tal log ra phy. Both com pounds were un sta ble in chlo ro form so lu tion and fur ther ox i dized to the cor re spond ing peroxy hemiacetal de riv a tives.

Two new oxygenated diterpenes, fusicoccanin and neofusicoccantriepoxide, were isolated and identified from the Taiwanese liver wort Plagiochila peculiaris. The latter compound possesses a methyl-rearranged fusicoccane skeleton. In addition, known secoaromadendranes and macrocyclic chloro-bisbibenzyls were also isolated from the polar fraction. P. peculiaris rep resents a very complex chemo-type of this genus.

The sesquiterpene constituents of the essential oils of the Taiwanese liverworts Lepidozia fauriana and L. vitrea were investigated. 11,12-Dihydrochiloscyphone and 7,10-anhydro-11,12-dihydrochiloscypholone were isolated from L. fauriana and spectroscopically characterised together with their hydrogenation products. From the same species three amorphane derivatives amorpha-4,9-dien-14-al, amorpha-4,9-dien-2-ol and 7,14-anhydroamorpha-4,9-diene, and from L. vitrea two oxygenated elemanes, namely 7-acetoxy-elema-1,3-dien-8-ol and elema-1,3-dien-7-ol, were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations in conjunction with enantioselective gas chromatography were utilized to establish absolute configurations.

Two minor diterpenoids, 15(16)-peroxy-3, 13-clerodadien-18-oic acid (4) and totarol (7), were isolated from the liverwort Schistochila acuminata. The former is a further oxidized cyclic peroxide from the major component. The latter is a rearranged abietane alcohol which skeleton was found in liverworts for the first time.

Five new ptychantins, J-N, along with two known ones, G and I, were isolated from the liverwort Ptychanthus striatus. Their structures were established by NMR spectroscopic analyses.

The mint plant, Teucrium marum (family Labiatae), sometimes called cat thyme, contains two methylcyclopentanoid monoterpenes, dolichodial and teucrein. The former compound is potently anti-insectan. It is repellent to ants (Monomorium pharaonis) and induces preening reflexes in flies (Phormia regina) and cockroaches (Periplaneta americana). Evidence is presented suggesting that dolichodial, which is presumed to be the plant's chief defensive agent, is stored in the tiny epidermal capsules that beset the leaves. It is only when the leaves are injured (and the capsules ruptured) that the leaves become repellent. Teucrein, in contrast, has no anti-insectan potency. It is present predominantly in the leaf buds, unlike dolichodial, which is present mostly in mature leaves. It is argued that teucrein is the storage compound from which dolichodial is generated during leaf development.

Thirteen specimens of Heteroscyphus coalitus were chemically examined. Among the isolated compounds, 1-hydroxyaromadendr-4-en-3-one has not been reported previously. A third new chemotype with kauranoids as the major constituents for the liverwort H. coalitus was identified.

Platelet activation is involved in serious pathological situations, including atherosclerosis and restenosis. It is important to find efficient antiplatelet medicines to prevent fatal thrombous formation during the course of these diseases. Marchantinquinone, a natural compound isolated from Reboulia hemisphaerica, inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 units mL−1), platelet-activating factor (PAF; 2 ng mL−1), collagen (10 μg mL−1), arachidonic acid (100 μm), or U46619 (1 μm) in rabbit washed platelets. The IC50 values of marchantinquinone on the inhibition of platelet aggregation induced by these five agonists were 62.0 ± 9.0, 86.0 ± 7.8, 13.6 ± 4.7, 20.9 ± 3.1 and 13.4 ± 5.3 μm, respectively. Marchantinquinone inhibited thromboxane B2 (TxB2) formation induced by thrombin, PAF or collagen. However, marchantinquinone did not inhibit TxB2 formation induced by arachidonic acid, indicating that marchantinquinone did not affect the activity of cyclooxygenase and thromboxane synthase. Marchantinquinone did inhibit the rising intracellular Ca2+ concentration stimulated by the five platelet-aggregation inducers. The formation of inositol monophosphate induced by thrombin was inhibited by marchantinquinone. Platelet cAMP and cGMP levels were unchanged by marchantinquinone. The results indicate that marchantinquinone exerts antiplatelet effects by inhibiting phosphoinositide turnover.

Seven kaurane-type diterpenoids were isolated from the Taiwanese liverworts Jungermannia truncata. Among them, three are new structures. They are: ent-16-kauren-3, 15-dione (6), ent-16(S)-kauran-3,15-dione (7), and ent-14α-hydroxy-16-kauren-15-one (11). From Plagiochila pulcherrima, three known kaurane alcohols were also isolated along with sesquiterpenoids plagiochilines A, B, C and ent-4β, 10α-dihydroxyaromadendrane.

Two Taiwanese liverworts, Jungermannia appressifolia and J. infusca , were chemically investigated. Jungermannia appressifolia elaborated two new labdane-type diterpenoids, labda-7,14-dien-9,13-diol and 13-hydroxy-7-oxo-labda-8,14-diene, along with the known labda-8,14-dien-13-ol. Jungermannia infusca produced two macrocyclic bis(bibenzyls), marchantin C and riccardin C, as its major constituents demonstrating the fourth chemo-type of this complex species.

The antioxidant activity of marchantin H was investigated using various experimental models. Marchantin H inhibited nonenzymatic iron-induced lipid peroxidation in rat brain homogenates with an IC50 value of 0.51 +/- 0.03 microM. It was more potent than desferrioxamine or other classical antioxidants. Marchantin H also suppressed NADPH-dependent microsomal lipid peroxidation with an IC50 value of 0.32 +/- 0.01 microM without affecting microsomal electron transport of NADPH-cytochrome P450 reductase. Marchantin H could scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl and peroxyl radical derived from 2,2 '-azobis(2-amidinopropane) dihydrochloride in aqueous phase, but not the peroxyl radical derived from 2,2 '-azobis(2,4-dimethylvaleronitrile) in hexane. The oxygen consumption during peroxyl radical-induced human erythrocyte ghost oxidation was decreased in a concentration-dependent manner by marchantin H. Furthermore, it was reactive toward superoxide anion generated by the xanthine/xanthine oxidase system. On the other hand, marchantin H inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity, thiobarbituric acid-reactive substance formation, and electrophoretic mobility in a concentration-dependent manner. Our results indicate that marchantin H is a potentially effective and versatile antioxidant and can be used as a chaperone protecting biomacromolecules against peroxidative damage.

Five new sequiterpenoids and three new marchantin-type compounds were isolated from the Taiwanese liverwort Reboulia hemisphaerica together with the previously known marchantinquinone and marchantin C. The structures were established by spectral analysis. Marchantinquinone displayed prominent antiplatelet activities. Three chemotypes are observed for this species.

Three novel sesquiterpenoids have been isolated from the Taiwanese liverworts Lepidozea vitrea and L. fauriana. Their structures were determined by extensive spectroscopical and X-ray analyses. The absolute configurations were derived by optical data.

Nudenoic acid, a new sesquiterpene possessing a novel tricyclic skeleton, was isolated from a Taiwanese liverwort Mylia nuda. The structure of nudenoic acid was determined by spectroscopic means and X-ray analysis.

Significance from the chemotaxonomic viewpoint is discussed on the basis of previous studies and recent findings on the chemical constituents of Taiwanese liverworts.

Three new sesquiterpenes, (−) -tridensone, (+) -aristol-9-en-12β-al and (+)-aristol-9-en-12β-oic acid have been isolated from the liverwort Bazzania tridens , together with the known sesquiterpenoids, (+)-cyclocolorenone and (−)-6S,7S-α-bisabolol. A comparison was also made on the constituents of seven samples of B. tridens samples collected from both Taiwan and Japan.

Three cis-clerodane-type acids 3-5 and one methyl ester 9 were identified from the liverwort Schistochila acuminata. The two new acids 3 and 5 were 12E and 12Z geometric isomers and the methyl ester 9 was first reported from nature.

Commercial Sep-Pak cartridges (Si or C 18 ) with a piece of short PTFE tubing could be used directly without any cooling or heating as a convenient and efficient collection device for preparative gas chromatography. Four sets of experimental results are presented.

The sesquiterpene aldehyde, tridensenal, of previously unknown skeleton was isolated from the Taiwanese liverwort Bazzania tridens. The structure of tridensenal was elucidated on the basis of spectral data and proved by synthesis of the diastereomeric mixture.

Isocostunolide is a sesquiterpene lactone isolated from the roots of Inula helenium. Its chemical structure was determined by NMR and FAB-MS spectra. No biological activities of this compound have yet been reported. In this study, we found isocostunolide could effectively induce cytotoxicity in three cancer cell lines (A2058, HT-29, and HepG2), with an IC(50) of 3.2, 5.0, and 2.0 micro g/mL, respectively. DNA flow cytometric analysis indicated that isocostunolide actively induced apoptosis of cancer cells accompanied by a marked loss of G0/G1 phase cells. To address the mechanism of the apoptotic effect of isocostunolide, we analyzed the induction of apoptosis-related proteins in A2058. The levels of pro-caspase-8, Bid, pro-caspase-3, and poly(ADP-ribose) polymerase (PARP) decreased. However, the level of Fas was increased markedly in a dose-dependent manner. Furthermore, this compound markedly induced a depolarization of mitochondrial membranes to facilitate cytochrome c release into cytosol. The findings suggest that isocostunolide may activate a mitochondria-mediated apoptosis pathway. To address this, we found that isocostunolide-induced loss of mitochondrial membrane potential occurred via modulation of the Bcl-2 family proteins. The production of intracellular reactive oxygen species (ROS) in A2058 was not elicited. In summary, for the first time, we have isolated and characterized isocostunolide from I. helenium. This compound induces apoptosis through a mitochondria-dependent pathway in A2058 cells.

Makinin, a new diterpenoid with a 17(15 → 16)abeoabietane skeleton, was isolated from the Taiwanese liverwort Makinoa crispata . The structure of makinin was deduced by spectroscopic analysis.

(−)-Ledol was found in the liverwort Cephaloziella recurvifolia along with other known sesquiterpenes. This is the first natural occurrence of this enantiomer of ledol. This is also the first chemical study on this family. Confusing assignments for ledol, globulol and viridiflorol in the literatures are discussed in this paper.

The essential oils and extracts of Mylia taylorii and M. nuda were investigated by gas chromatography, mass spectrometry, NMR spectroscopy and chemical correlations. Beside several known compounds 13 new constituents including three new carbon skeletons could be identified. Four hydrocarbons with a molecular formula of C 15 H 22 ( m / z 202) were identified as myli-4(15)-ene ( 1 ), aromadendra-1(10),4(15)-diene ( 19 ), aromadendra-4,10(14)-diene ( 20 ) and aromadendra-4,9-diene ( 21 ). Three oxaspiro-compounds were identified as 7- epi -bourbon-3-en-5,11-oxide ( 22 ), guai-3,10(14)-dien-5,11-oxide ( 23 ) and guai-3,9-dien-5,11-oxide ( 24 ). The absolute configuration of myli-4(15)-en-3-one ( 5 ) could be established by chemical correlation. Together with α-taylorione ( 7 ) the corresponding 6,11- seco -compound taylopyran ( 25 ) with a new carbon skeleton was identified which serves as a precursor to taylocyclane ( 26 ) and taylofuran ( 27 ). Taynudol ( 28 ) contains a new carbon skeleton with a cyclobutenyl structure.

One naphthalene and three isocoumarin derivatives have been isolated from the Taiwanese liverwort Wettsteinia inversa . Their structures were determined by extensive spectroscopical analysis. The significance from the chemotaxonomical point of view is discussed. In addition, the isocoumarin inversin displayed potent antiplatelet activities.

A novel gymnomitrane-type alcohol was identified from the liverwort Cylindrocolea recurvifolia. The structure of this new compound was confirmed by X-ray analysis. This is the first report on the chemical constituents of this genus.

The new sesquiterpene hydrocarbon, cyclomyltaylane, has been isolated from the Taiwanese liverwort Bazzania tridens. Its structure was deduced mainly from various 1D and 2D NMR data.

The ether extract of the Chilean liverwort Lepicolea ochroleuca yielded three sesquiterpenoids, ent -4β-Hydroxy-10α-methoxyaromadendrane, ent -3β-Hydroxyspathulenol, and 1,10-Dioxotayloriane, as minor components.The major components were ledol and 13- epi -neoverrucosan-5β-ol, four other minor fusicoccanoids were identified.

Two bisabolene sesquiterpenes (1 and 2), two nor-sesquiterpene ketones (3 and 4) and one humulene epoxide (6) were identified from the Taiwanese liverwort Bazzania tridens. Among them, 3 was novel, and 2, 4 and 6 were reported for the first time from a natural source. Their structures were mainly elucidated by analysis of various NMR spectra.

Nudenoic acid, a new sesquiterpene possessing a novel tricyclic skeleton, was isolated from a Taiwanese liverwort Mylia nuda. The structure of nudenoic acid was determined by spectroscopic means and X-ray analysis.

Two diterpenoids, (+)-labda-7,14-dien-13-ol and (+)-manoyl oxide, and one bis(bibenzyl) compound, isomarchantin C, were isolated as the major components from the Taiwanese liverwort Mylia nuda. The spectral evidence is discussed in this paper. In addition, several monoterpenes and sesquiterpenes were also identified by GC/MS.

By spectral properties and chemical correlation, the structures of two related new sesquiterpenes, isobazzanene and isocyclobazzanene, were proposed to be 1 and 2 , respectively.

The liverwort, Scapania ornithopodioides, was investigated for sesquiterpene hydrocarbons by utilizing GC and GCIMS and 17 components were identified. Among these, the major component, aromadendrene, and two minor ones, cyclosativene and α-farnesene are reported for the first time as constituents of liverworts. In addition, aromadendrene also occurred in three other Taiwanese liverworts examined.