New Helvolic Acid Derivatives with Antibacterial Activities from Sarocladium oryzae DX-THL3, an Endophytic Fungus from Dongxiang Wild Rice (Oryza rufipogon Griff.).

Three new helvolic acid derivatives (named sarocladilactone A (1), sarocladilactone B (2) and sarocladic acid A (3a)), together with five known compounds (6,16-diacetoxy-25-hy- droxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (3b), helvolic acid (4), helvolinic acid (5), 6-desacetoxy-helvolic acid (6) and 1,2-dihydrohelvolic acid (7)), were isolated from the endophytic fungus DX-THL3, obtained from the leaf of Dongxiang wild rice (Oryza rufipogon Griff.). The structures of the new compounds were elucidated via HR-MS, extensive 1D and 2D NMR analysis and comparison with reported data. Compounds 1, 2, 4, 5, 6 and 7 exhibited potent antibacterial activities. In particular, sarocladilactone B (2), helvolinic acid (5) and 6-desacetoxy-helvolic acid (6) exhibited strongly Staphylococcus aureus inhibitory activity with minimum inhibitory concentration (MIC) values of 4, 1 and 4 µg/mL, respectively. The structure-activity relationship (SAR) of these compounds was primarily summarized.

Carbazole alkaloids isolated from the branch and leaf extracts of Clausena lansium.

The present study carried out a phytochemical investigation of the methanol extract of the branches and leaves of Clausena lansium and afforded nine carbazole alkaloids (compounds 1-9) including two new carbazole alkaloids, claulansiums A and B (compounds 1 and 2). The new compounds were elucidated on the basis of extensive spectroscopic data (MS, NMR, IR, and UV) and the known compounds were identified by comparing spectroscopic data with those reported in literature. All the isolated compounds were tested for their cytotoxic activity against A549 and Hela cancer cell lines. Our results showed that compounds 2-6 exhibited varying degrees of cytotoxicity to cancer cells, with IC50 values ranging from 8.67 to 98.89 µmol·L-1.

Report: Cytotoxic flavonoids from the young twigs and leaves of Caesalpinia bonduc (Linn) Roxb.

The extraction, fractionation and recognition of flavonoids from the ethanolic extract of young twigs and leaves of C. bonduc were carried out. In addition, cytotoxic study of the flavonoids on two cancer cell lines, BGC-823 and HeLa was carried our using sulphorhodamine B assay. Seven flavonoids, six of which are being reported for the first time in this plant, were isolated. Their structures were identified by MS and NMR spectroscopic methods. Petroleum ether, ethyl acetate and water fractions exhibited moderate cytotoxic activity against HeLa cells. Five compounds showed cytotoxic activity against HeLa cell in comparison with Paclitaxel, while only one compound showed a good degree of cytotoxic activity against BGC-823 cell in comparison to Paclitaxel. The results obtained showed a structure - activity relationship.

[Flavone C-glycosides from seeds of Ziziphus jujuba var. spinosa].

Five flavone C-glycosides were isolated from the methanol extract of the degrease seeds of Ziziphus jujuba var. spinosa though various column chromatography methods including silica gel, MPLC, and HPLC. The structures were elucidated as 6"-feruloyl- 6'''-vanillylspinosin(1), 6",6'"-diferuloylspinosin(2), spinosin(3), swertisin(4) and isoswertisin(5) based on the NMR and MS spectral data. 1 is a new compound.

Coumarins from roots of Clausena excavata.

Two new coumarins, clauexcavatins A (1) and B (2), along with seven known ones (3-9), were isolated from the roots of Clausena excavata Burm. f. (Rutaceae). Their structures were elucidated on the basis of spectral data.

Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin isolated from Inula helianthus-aquatica.

Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan, China. The potent apoptotic activities of bigelovin in human leukemia U937 cells were shown in our previous study. The present study investigated the anti-angiogenic and immunomodulatory effects of bigelovin using transgenic zebrafish Tg(fli1a:EGFP)y1 with fluorescent blood vessels and human peripheral blood mononuclear cells (PBMCs), respectively. Furthermore, the inhibitory activities of bigelovin on the human endothelial cell adhesion molecules (CAMs) were also examined. Our results showed that the growth of subintestinal vessels of the bigelovin-treated zebrafish embryos was significantly inhibited and the gene expressions in angiogenesis signaling pathways (e.g. Ang2 and Tie2) of the zebrafish were down-regulated after bigelovin treatment. Besides, the proliferation and Th1 cytokines productions (e.g. IFN-γ, IL-2 and IL-12) were suppressed in bigelovin-treated PBMCs. On the other hand, bigelovin was shown to significantly inhibit the human monocyte adhesion to human endothelial cells and the gene expressions of inflammation-related CAMs (e.g. ICAM-1, VCAM-1 and E-selectin) were significantly down-regulated in bigelovin-treated human endothelial cells. In summary, our data provide the first evidence that bigelovin possesses anti-angiogenic and immunomodulatory activities, suggesting bigelovin may exert multi-target functions against cancer in animal models.

[Chemical constituents contained in ethanol extracts from Acorus tatarinowii and their anti-fatigue activity].

Chemical constituents in ethyl acetate and butanol fractions of ethanol extracts from Acorus tatarinowii were separated by column chromatography. Bufo skeletal muscle fatigue model was established to study the anti-fatigue activity of separated compounds. Five compounds were separated and identified by spectroscopic analysis as acoramone(1),cycloartenone(2),2,4,5-trimethoxyl-2'-butoxy-1,2-phenyl propandiol(3),5-hydroxymethyl furfural(4), and 5-butoxymethyl furfural(5). Compound 3 was a new compound, and compounds 2 and 5 were separated from this plant for the first time. Compound 4 exhibited a notable anti-fatigue activity.

Terpene and lignan glycosides from the twigs and leaves of an endangered conifer, Cathaya argyrophylla.

Labdane diterpene glycosides cathargyroside A and cathargyroside B, monoterpene glycosides vervenone-10-O-ß-D-glucopyranoside and vervenone-10-O-ß-D-apiofuranosyl-(1″→6')-ß-D-glucopyranoside, as well as lignan glycosides cedrusinin-4-O-α-L-rhamnopyranoside and (+)-cyclo-olivil-9'-O-ß-D-xylopyranoside, along with 39 known compounds, were obtained from the methanol extract of the twigs and leaves of Cathaya argyrophylla. These compounds were identified mainly by analyzing their NMR and MS data. Almost all of these compounds were hitherto unknown in this genus. The isolated compounds were screened against Candida albicans and Staphylococcus aureus for antimicrobial assay, and against K562, HT-29, BEL-7402, SGC-7901, B16, BGC-823, U251 and A549 cancer cell lines for cytotoxic activities. One compound showed antimicrobial activity against C. albicans, and four of them displayed cytotoxicity. Similarity analysis on the chemical constituents of the genera Cathaya, Picea and Pinus supported their close phylogenetic relationships.

Zizimauritic acids A-C, three novel nortriterpenes from Ziziphus mauritiana.

Zizimauritic acids A-C (1-3), three novel nortriterpenes with a unique A-nor-E-seco spiro-lactone ceanothane-type triterpene skeleton, together with 3 known triterpenes ceanothenic acid (4), betulinic acid (5), and ceanothic acid (6), were isolated from the roots of Ziziphus mauritiana. Compounds 1-4 showed cytotoxicities with the IC(50) values ranging from 5.05 to 11.94 µg/ml, and compounds 1 and 3 showed an inhibitory effect on the growth of Staphylococcus aureus with the IC(50) values 2.17 and 12.79 µg/ml. A plausible biosynthetic pathway of compounds 1-3 was proposed.

Cyclopeptide Alkaloids from Ziziphus apetala.

Six novel Ia3-type cyclopeptide alkaloids (1-6) were isolated from stems of Ziziphus apetala. Compound 5 and the known compounds mauritine A (7) and mauritine F (8) were isolated from the roots. Their structures were determined by spectroscopic analyses and chemical methods. The total alkaloids from the roots and the isolated cyclopeptide alkaloids were tested for antidepressant behavior on mice, cytotoxicity, and 11ß-hydroxysteroid dehydrogenase (11ß-HSD) inhibition in vitro. Only mauritine A (7) showed inhibitory activity on 11ß-HSD1, with IC50 values of 52.0 (human) and 31.2 µg/mL (mouse).

Biologically active arborinane-type triterpenoids and anthraquinones from Rubia yunnanensis.

Twelve new arborinane-type triterpenoids (1-12) and four new anthraquinones (13-16), together with 50 known compounds, were isolated from the roots of Rubia yunnanensis. The structures of 1-16 were elucidated by spectroscopic data analysis and chemical methods. All compounds were evaluated for their cytotoxic, antibacterial, and antifungal activities. Rubiyunnanol C (5) is the first example of an arborinane-type triterpenoid with a double bond at C-8-C-9.

A new norlignan from Taxodium ascendens.

A new norlignan, (2R,3R,4S,5S)-2,4-bis(4-hydroxyphenyl)-3,5-dihydroxy-tetrahydropyran (1), together with 9 known compounds were isolated from the branches and leaves of Taxodium ascendens. Their structures were mainly determined on the basis of MS, IR, 1D and 2D NMR spectral evidences. Methanol extract showed inhibitory activity on carbonic anhydrase II with an IC(50) value of 4.27 microg/ml, acetone extract and methanol extract inhibited activity of cathepsin B with IC(50) values of 2.12 and 3.71 microg/ml, respectively.

Apoptosis inducement of bigelovin from Inula helianthus-aquatica on human Leukemia U937 cells.

Inula helianthus-aquatica C. Y. Wu is a traditional medicinal plant used to treat some cancers in folk herbal medicine of Yunnan, China. Bigelovin, a sesquiterpene lactone isolated from this herb, potently inhibits the growth of a panel of eight cancer cell lines, especially in human monoblastic leukemia U937 cells with an IC(50) value of 0.47 microM. Characteristic morphological features of apoptosis were observed in U937 cells treated with bigelovin. Annexin V and nuclear DNA content distribution assays showed that the percentage of Annexin V positive cells increased to 8.86% (24 h) with 1 microM bigelovin treatment, and cells treated with bigelovin at this concentration apparently arrested at G(0)/G(1) phase compared with the control. These data suggested that cytotoxic effect of bigelovin on U937 cells involves induction of apoptosis, and the cell cycle is arrested at G(0)/G(1) phase.

Natural inhibitors of DNA topoisomerase I with cytotoxicities.

DNA Topoisomerase I can cause DNA breaks and play a key role during cell proliferation and differentiation. It is an important target for anticancer agents. While screening for anticancer compounds, seven natural compounds, 1-7, showed potent cytotoxicities against a panel of ten cancer cell lines. Moreover, an inhibition assay demonstrated that they are also DNA topoisomerase I inhibitors, in which inhibitors 1-5 are new ones.