Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis.

Ovarian cancer is one of the leading causes of cancer deaths worldwide in women, and the most malignant cancer among the different gynecological cancers. In this study, we explored potentially anticancer compounds from Cornus walteri (Cornaceae), the MeOH extract of which has been reported to show considerable cytotoxicity against several cancer cell lines. Phytochemical investigations of the MeOH extract of the stem and stem bark of C. walteri by extensive application of chromatographic techniques resulted in the isolation of 14 compounds (1-14). The isolated compounds were evaluated for inhibitory effects on the viability of A2780 human ovarian carcinoma cells and the underlying molecular mechanisms were investigated. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to assess the anticancer effects of compounds 1-14 on A2780 cells, which showed that compound 11 (betulinic acid) reduced the viability of these cells in a concentration-dependent manner and had an half maximal (50%) inhibitory concentration (IC50) of 44.47 µM at 24 h. Nuclear staining and image-based cytometric assay were carried out to detect the induction of apoptosis by betulinic acid. Betulinic acid significantly increased the condensation of nuclei and the percentage of apoptotic cells in a concentration-dependent manner in A2780 cells. Western blot analysis was performed to investigate the underlying mechanism of apoptosis. The results indicated that the expression levels of cleaved caspase-8, -3, -9, and Bax were increased in A2780 cells treated with betulinic acid, whereas those of Bcl-2 were decreased. Thus, we provide the experimental evidence that betulinic acid can induce apoptosis in A2780 cells through both mitochondria-dependent and -independent pathways and suggest the potential use of betulinic acid in the development of novel chemotherapeutics for ovarian cancer therapy.

Ellagitannins of Davidia involucrata. I. Structure of Davicratinic Acid A and Effects of Davidia Tannins on Drug-Resistant Bacteria and Human Oral Squamous Cell Carcinomas.

We isolated a new ellagitannin, davicratinic acid A (5), together with four known ellagitannins, davidiin (1), granatin A (2), pedunculagin (3), and 3-O-galloylgranatin A (4), from an aqueous acetone extract of dried Davidia involucrata leaves. The known ellagitannins were identified based on spectroscopic data. The structure of davicratinic acid A (5), a monomeric ellagitannin possessing a unique, skew-boat glucopyranose core, was established based on spectroscopic data. Additionally, we examined the effects of several tannins with good yields from this plant on drug-resistant bacteria and human oral squamous cell carcinomas, and found that davidiin (1) exhibited the most potent antibacterial and antitumor properties among the tannins examined.

Five new taraxerene-type triterpenes from the branch barks of Davidia involucrata.

Five new taraxerene-type triterpenes, 2-nor-D-friedoolean-14-en-28-ol (1), 2-nor-d-friedoolean-14-en-3α,28-diol (2), 6α-hydroxy-2-nor-D-friedoolean-14-en-3,21-dione (3), 6α,11α,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (4), and 6α,23,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (5), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with five known compounds. Their structures were elucidated by means of various spectroscopic analyses. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404.

Anti-inflammatory activities of methanol extract of Mastixia arborea C.B. Clarke as to mouse macrophage and paw edema.

The biological activity of Mastixia arborea (MA) relates to inflammation, but the underlying mechanisms are largely unknown. We confirmed the anti-inflammatory effects of a methanol extract of MA extract on lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells and carrageenan-induced mice paw edema. The MA extract significantly inhibited nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1ß (IL-1ß), and IL-6 production in LPS-stimulated RAW264.7 cells. In vitro expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was suppressed by the extract. The extract attenuated acute inflammatory responses in carrageenan-induced mice paw edema. A mechanism study indicated that translocation of the NF-κB (p65) subunit into the nucleus and phosphorylation of ERK and JNK were inhibited by the extract. These results indicate that the extract is an effective suppressor of the inflammatory response, blocking the phosphorylation of ERK and JNK and the translocation of NF-κB in macrophages, thereby producing an anti-inflammatory effect in vivo.

[Studies on the chemical constituents of Toricellia angulata var. intermedia].

OBJECTIVE: To study the chemical constituents of Toricellia angulata var. intermedia. METHODS: The constituents were isolated and purified by repeated column chromatography and their structures were elucidated by spectroscopic analysis. RESULTS: Twelve compounds including beta-sitoterol (1), 7-hydroxy-3-ethylphthalide (2), 3beta-methoxy-stigmast-7-ene (3), stigmast-5-ene (4), trans-p-methylcinnamaldehyde (5), stigmate-7-en-3beta-ol (6), o. p-dimethoxybenzoicacid (7), beta-daucosterol (8), ursolicacid (9), stearic acid (10), docosanoic acid (11), palmitic acid (12) were isolated and identified from this plant. CONCLUSION: All the compounds are isolated from the plant for the first time, compounds 3 -7, 10 -12 are isolated from this genus for the first time.

Curtisia dentata (Cornaceae) leaf extracts and isolated compounds inhibit motility of parasitic and free-living nematodes.

Haemonchus contortus and Trichostrongylus colubriformis are among the most important parasitic nematodes of small ruminants. Caenorhabditis elegans, a free-living nematode, is used as a model for evaluating anthelmintic activity of a variety of test substances. Extracts of several medicinal plants are useful in vitro and in vivo against nematode development. Extracts of Curtisia dentata, a South African medicinal plant, and compounds isolated from leaves of this plant were investigated for anthelmintic activity against T. colubriformis, H. contortus and C. elegans. The acetone and dichloromethane extracts were active against all nematodes at concentrations as low as 160 microg/ml. Betulinic acid and lupeol were active against the parasitic nematodes only at the high concentrations of 1000 and 200 microg/ml, respectively. All compounds were effective against C. elegans with active concentrations as low as 8 microg/ml. Betulinic acid was less active than lupeol and ursolic acid against C. elegans. The acetone and dichloromethane extracts were also active against C. elegans with a concentration of 0.31 mg/ml resulting in almost 80% inhibition of larval motility. The use of free-living nematodes may provide information on the activity of potential anthelmintics against parasitic nematodes. Extracts of various medicinal plant species may provide solutions to ill-health of small ruminants caused by parasitic nematodes in poor communities of southern Africa.

Four pentacyclic triterpenoids with antifungal and antibacterial activity from Curtisia dentata (Burm.f) C.A. Sm. leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Curtisia dentata is used in southern Africa to treat various diseases of bacterial and fungal origin in humans and animals to such a degree that the species is vulnerable and declining [Dold, A.R., Cocks, M.L., 2001. Traditional veterinary medicine in the Alice district of the Eastern Cape Province, South Africa. South African Journal of Science 97, 375-379]. Preliminary studies indicated good activity against Candida albicans. AIM OF THE STUDY: The phytochemistry and antimicrobial activity of this plant species has not been extensively investigated, and a closer examination of the compounds responsible for antimicrobial activity was warranted. MATERIALS AND METHODS: Broth microdilution assay and bioautography were used to evaluate antibacterial and antifungal activity in Curtisia dentata leaf extracts and fractions. Bioassay-directed fractionation using column chromatography yielded four compounds characterised by spectroscopic methods. RESULTS: Lupeol (1), betulinic acid (2), ursolic acid (3) and 2alpha-hydroxyursolic acid (4) were isolated from Curtisia dentata leaves. Betulinic acid, ursolic acid and 2alpha-hydroxyursolic acid appreciably inhibited fungal growth with MIC values ranging from 8 to 63mug/mL. CONCLUSIONS: The isolation of four antibacterial and antifungal triterpenoids is reported for the first time from Curtisia dentata. This study provides information on the antimicrobial compounds of this species, as well as a preliminary rationale for the use in traditional South African medicine.

[Studies on chemical constituents from Davidia involucrata var. vilmoriniana].

OBJECTIVE: To study the chemical constituents of Davidia involucrata var. vilmoriniana. METHOD: The chemical constituents were isolated by column chromatography on silical gel and sephadex LH -20. Their structures were elucidated on the basis of spectral analysis and physical constants. RESULT: Seven compounds were isolated from this plant and the structures of them were identified as 3, 4, 5-trihydroxybenzoic acid (1), ellagic acid (2), maleic acid (3), quercetin (4), quercetin-3-O-beta-D-galactoside (5), 2alpha, 3alpha, 19alpha, 23-tetrahydroxyurs-12-en-28-oic-acid-28-O-beta-D-glucopyranosyl ester (6), ethyl brevifolin carbosylate (7), respectively. CONCLUSION: Compounds 1-7 were isolated from this plant for the first time.

[Studies on chemical constituents of Helwingia chinensis].

OBJECTIVE: To investigate the chemical constituents of Helwingia Chinensis. METHOD: Compounds were isolated with silica gel, Sephadex LH - 20 and polyamide chromatography, and their structures were elucidated by means of spectral analysis. RESULT: Six compounds were isolated and identified as cinnamic acid (1), gult-5-en-3beta-ol (2), friedelin (3), alpha-amyrin (4), luteolin-7-O-beta-D-glucoside (5) and 4, 5-dimethoxy-1, 2-benzoquinone (6). CONCLUSION: All these Compounds were obtained from H. chinensis for the first time.

Neolignan and lignan glycosides from branch bark of Davidia involucrata.

Two new neolignan glycosides, davidioside A (1) and davidioside B (2), have been isolated along with six known compounds from the branch bark of Davidia involucrata. Identification of their structures was achieved by 1D and 2D NMR experiments, including (1)H-(1)H COSY, NOESY, HMQC, and HMBC methods as well as FAB mass spectral data.

Phenolic glucosides from Alangium plantanifolium.

A novel phenolic glucoside alangitanifoliside A (1) together with two known phenolic glucosides 4',6'-O-(S)-hexahydroxydiphenylsalicin (2) and salicin (3), and gallic acid were isolated from stem barks of Alangium plantanifolium. Their structures were determined by spectroscopic and chemical methods. The structure of 1 was elucidated to be 1-O-[2-(1-hydroxy-6-oxocyclohex-2-ene-1-carboxymethyl)-phenyl]-4,6-O-[(S)-,4,4',5,5' 6,6'-hexahydroxydiphenoyl]-beta-D-glucopyranose.

Ellagic acid formation from galloylglucoses by a crude enzyme of Cornus capitata adventitious roots.

The aqueous extract of acetone powder, which had been prepared from Cornus capitata 'Mountain Moon' adventitious roots, cultured in MS medium with a high concentration of Cu2+(10 microM), showed strong oxidative activity toward galloylglucoses. A compound formed from galloyglucoses, such as 1,2,3,4,6-penta-O-galloyl-beta-D-glucose and tannic acid, by the reaction with the crude enzyme solution of the adventitious roots was isolated and characterized as ellagic acid by spectrometric analyses.

Glycosides of benzyl and salicyl alcohols from Alangium chinense.

From the water-soluble fraction of the dried leaves of Alangium chinense, three new glycosides, benzyl alcohol beta-D-glucopyranosyl-(1 --> 2)-[beta-D-xylopyranosyl-(1 --> 6)]-beta-D-glucopyranoside, 2'-O-beta-D-glucopyranosylsalicin, and 2'-O-beta-D-glucopyranosyl-6'-O-beta-D-xylopyranosylsalicin were isolated along with seven known glycosides. The structures of the new compounds were determined by spectroscopic and chemical means.