Steroids with inhibitory activity against the prostate cancer cells and chemical diversity of marine alga Tydemania expeditionis

A new diketosteroid, (E)-stigmasta-24(28)-en-3,6-dione (1), along with three known steroids (2-4) was isolated from marine alga Tydemania expeditionis collected in China Sea. Their structures were elucidated by extensive spectroscopic methods. Comparison of the chemical constituents revealed significant diversity among different locations. The biological activities of 1, 3 and 4 were evaluated on the prostate cancer cell lines and androgen receptor. Compound 1 exhibited moderate inhibitory activities against the prostate cancer cells DU145, PC3 and LNCaP with IC(50) values of 31.27±1.50, 40.59±3.10 and 19.80±3.84 μM, respectively. Compound 3 showed more potent activities with IC(50) values of 12.38±2.47, 2.14±0.33 and 1.38±0.07 μM, respectively. However, compound 4 showed only weak inhibitory activities on LNCaP cells and was inactive on DU145 and PC3 cells. A competitive binding assay showed that compound 1 exhibited significant affinity to the androgen receptor with an IC(50) value of 7.19±0.45 μM, while 3 and 4 were inactive. The fact that the inhibitory properties of 1 and 3 against the prostate cancer cells were inconsistent with their affinities to the androgen receptor suggested that there might be other mechanism of action involved in the cytotoxic activity.     

Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don

The ethanolic extract from stems of a Thai medicinal plant, Alstonia macrophylla Wall. ex G. Don (Apocynaceae) showed a significant inhibitory effect on acetylcholinesterase (AChE) determined by using Ellman assay. Four compounds i.e., a bisindole alkaloid, macralstonine (1), a new bisindole alkaloid, thungfaine (2), a secoiridoid glycoside, sweroside (3) and a new secoiridoid glycoside, naresuanoside (4) were isolated. Compound 4 showed moderate AChE and butyrylcholinesterase (BChE) inhibitory effects. Interestingly, compound 4 inhibited cell growth on human androgen-sensitive prostate cancer cell line (LNCaP) but no effect on viability of human foreskin fibroblast cells (HF).     

Antiproliferative activity of Saponaria vaccaria constituents and related compounds

Total methanolic extracts of Saponaria vaccaria seed derived from several varieties, as well as various purified components obtained through successive chromatographic separations of total extracts were evaluated for their growth inhibitory activity in WiDr (colon), MDA-MB-231 (breast), NCI-417 (lung) and PC-3 (prostate) human cancer cells as well as the non-tumorigenic fibroblast BJ (CRL-2522) cell line using MTT colorimetric assay. Purified bisdesmosidic saponins segetoside H and I were further examined using microscopy and apoptosis assays. Bisdesmosidic saponins exhibited dose-dependent growth inhibitory and selective apoptosis-inducing activity. Growth inhibitory effects were particularly strong in a breast (MDA-MB-231) and a prostate (PC-3) cancer cell line. Total extracts exhibited a different preference being most active against a colon cancer cell line (WiDr). In a comparison of varieties, all of the total seed extracts exhibited similar dose-dependent activities, but with some variation in potency. Monodesmosidic saponins vaccarosides A and B, phenolic vaccarin, and cyclopeptide segetalin A, co-occurring seed substituents, did not exhibit activity. The non-tumorigenic fibroblast cell line BJ (CRL 2522) was growth inhibited but did not undergo apoptosis when treated with bisdesmosidic saponins at low micromolar concentrations. Saponin-rich extracts from Kochia scoparia seed and Chenopodium quinoa were also evaluated alongside Saponaria saponins but did not exhibit activity. Closely related Quillaja saponins exhibited activity but were less potent.     

Iridoid, phenylethanoid and flavonoid glycosides from Sideritis trojana

From the MeOH extract of Sideritis trojana, a new iridoid glycoside, 10-O-(E)-feruloylmelittoside (1) was obtained in addition to four known iridoid glycosides [melittoside (2), 10-O-(E)-p-coumaroylmelittoside (3), stachysosides E (4) and G (5)]. Moreover, five phenylethanoid glycosides [verbascoside (6), isoacteoside (7), lamalboside (8), leonoside A (9), isolavandulifolioside (10), three flavone glycosides (isoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (11), 4'-O-methyisoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (12), 3'-hydroxy-4'-O-methyisoscutellarein 7-O-[6'-O-acetyl-β-allopyranosyl-(1→2)]-β-glucopyranoside (13) and a benzylalcohol derivative (di-O-methylcrenatin) were obtained and identified. The structures were elucidated on the basis of NMR and HRMS data. All compounds were tested for their antioxidant activity by in vitro TEAC assay and some of them exhibited moderate activity (0.97-1.44 mM) when compared with the reference compound (quercetin 1.86 mM). Glycosides 6-13, the most active compounds in the TEAC assay, were also tested by flow cytometry to evaluate their ability to affect the levels of reactive oxygen species (ROS) in human prostate cancer cells (PC3).     

A bioactive isoprenylated xanthone and other constituents of Garcinia edulis

Phytochemical investigation on the root bark of Garcinia edulis (Clusiaceae) gave a new isoprenylated xanthone, 1,4,6-trihydroxy-3-methoxy-2-(3-methyl-2-butenyl)-5-(1,1-dimethyl-prop-2-enyl)xanthone (1), a known xanthone, forbexanthone (2) together with three known pentacyclic triterpenoids, friedelin, lupeol and lupeol acetate. The structure of the new compound was fully characterised by NMR spectroscopic analysis. Compound 1 showed significant anti-HIV-1 protease activity with IC₅₀ value of 11.3 µg/mL. Furthermore, compound 1 showed potent cytotoxic activity with LC₅₀ value of 2.36 µg/mL against brine shrimp larva in vitro.     

Antioxidant activity of polyphenols from solid olive residues of c.v. Coratina

The antioxidant profile of extracts from solid olive residue (SOR) of c.v. Coratina, a cultivar widely diffused in the south of Italy, using both cell-free and cell-based experimental models, was investigated. A total hydroalcoholic extract (polyphenols content 19.7%) and a purified extract (Oleaselecttrade mark) (polyphenols content 35.1%) were tested for their ability to quench the stable free radical DPPH, the peroxyl radicals (ORAC assay), by monitoring the loss in fluorescence of R-phycoerythrin induced by the peroxyl radical generator AAPH and their ability to inhibit the cumene hydroperoxide-induced lysis of rat red blood cells (RBC). The total hydroalcoholic extract showed IC(50) 26.96+/-1.53 microg/ml in the DPPH assay, that 10 microg/ml were equivalent to 2.11+/-0.12 microg/ml Trolox (ORAC assay) and IC(50) 1.7+/-0.20 microg/ml in the RBC hemolysis. The Oleaselect extract was 4 to 5 folds more active than the hydroalcoholic extract in all the experimental models, with IC(50) values of 7.36+/-0.38 microg/ml in the DPPH test and of 0.38+/-0.03 microg/ml in RBC; the antioxidant activity in the ORAC assay was slightly greater than that of Trolox (10 microg/ml equivalent to 11.45+/-0.40 microg/ml). The scavenging effect of the extract in the ORAC assay was compared to that of verbascoside (the main polyphenol component) and of caffeic acid (the basic constituent of verbascoside): the results indicate that caffeic acid (10 microg/ml equivalent to 35.70+/-2.95 microg/ml Trolox) is more potent than verbascoside (10 microg/ml equivalent to 15.42+/-1.21 microg/ml Trolox) in entrapping peroxyl radicals. Finally the antioxidant activity of the Oleaselect extract was confirmed in human umbilical endothelial cells (EC) exposed to the site-specific peroxyl radical inducer AAPH, where a massive lipid peroxidation process (marker the fluorescence probe BODIPY) takes place, paralleled by a marked loss of cell viability (calcein assay). The purified extract (1-20 microg/ml) pre-incubated with EC for 1 h dose-dependently inhibited both the lipid-peroxidation damage and cell death. Taking into account the total polyphenol content, these results clearly indicate a greater antioxidant activity for the purified extract, due to a cooperative antioxidant interaction among its polyphenol constituents.     

Tithonia diversifolia and its main active component tagitinin C induce survivin inhibition and G2/M arrest in human malignant glioblastoma cells

We investigated the antitumour activity of Tithonia diversifolia (TD) on malignant glioblastoma cells. Our results suggested that tagitinin C was the main component in viability inhibition on malignant glioblastoma cells, and also accounted to be the most abundant component (> 65%) in TD extract. Both TD extract and tagitinin C exhibited vigorous potential to produce in vitro viability inhibition, autophagic cell death and G2/M arrest. Furthermore, the activity of survivin, a critical resistant-factor in cancer therapy, could be downregulated significantly by TD extract and tagitinin C. These findings suggested that TD extract and tagitinin C were effective for treating malignant glioblastoma.     

Molecular simulations of Taxawallin I inside classical taxol binding site of β-tubulin

A new taxoid Taxawallin I (1) along with two known taxoids (2-3) were isolated from methanolic bark extract of Taxus wallichiana Zucc. Structural characterization was confirmed by mass and NMR spectral techniques. Taxawallin I exhibited significant in-vitro anticancer activity against HepG2, A498, NCI-H226 and MDR 2780AD cancer lines. Tubulin binding assay was performed to assess its tubulin binding activity. Molecular docking analysis was performed to study the potential binding mode inside the taxol binding site of β-tubulin.     

Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma Coptis in HepG2 cells

Generally, berberine, coptisine, palmatine, and jatrorrhizine were considered as the main bio-active compounds in Rhizoma Coptis (RC). Little attention was paid to investigate the pharmacological activity of minor constituents in RC. The present study was designed to separate the minor compounds, and the cytotoxicity and antihyperglycemic effect of these compounds in HepG2 cells were also studied. Palmatine (1), berberine (2), coptisine (3), epiberberine (4), columbamine (5), and jatrorrhizine (6) from RC ethanol extract were isolated by high speed counter current chromatography (HSCCC) in one run. The remaining fraction (about 50% of extract in HSCCC) was further isolated by traditional column chromatography methods to yield magnoflorine (7), ferulic acid (8), and choline (9). Another four alkaloids, namely groenlandicine (10), berberrubine (11), oxyberberine (12), 8-oxo-coptisine (13), also were obtained from CHCl₃ extracts. Especially, choline was first isolated from RC. Cell assay indicated that the minor fractions excluding compounds 1-6 showed obvious glucose lowering activity. In addition, the minor monomers also exhibited moderate glucose lowering activity. The combination of berberine and ferulic acid showed synergistic effect on antihyperglycemic. The combination of alkaloids 1-6 was same so. All compounds had different cytotoxicity in HepG2 cells within the test concentration. Of them, berberrubine showed the strongest cytotoxicity. The results suggested that combined action of variety constituents contributed to the antihyperglycemic effets and low cytotoxicity of RC extract in HepG2 cells.     

Antioxidant xanthones from Swertia mussotii,a high altitude plant

Four new xanthones, 3,5,6,8-tetrahydroxyxanthone-1-C-β-d-glucoside (1), 7-hydroxy-3,4,8-trimethoxyxanthone-1-O-(β-d-glucoside) (2), 6-hydroxy-3,5-dimethoxyxanthone-1-O-(β-d-glucoside) (3), 3,4,7,8-tetramethoxyxanthone-1-O-(β-d-glucoside) (4), together with twenty-one known xanthones (5–25) were isolated from the ethanol aqueous extract of Swertia mussotii. Their structures were elucidated via spectroscopic analyses. Oxygen radical absorbance capacity of all the isolated xanthones was systematically evaluated by ORAC_FL assay. Results disclose that all the tested xanthones display moderate to excellent antioxidant activity, where 1 is the most active compound and 13 is the least one. A preliminary structure–activity relationship is also discussed.     

Stereospecificity of hydroxyl group at C-20 in antiproliferative action of ginsenoside Rh2 on prostate cancer cells

Prostate cancer is the fifth most common neoplasm worldwide, and the second most common cancer among men. Ginsenosides, the main component of ginseng, have been known for their medicinal effects such as anti-inflammatory and anti-proliferative activities. In this study, we investigated the inhibitory effects of ginsenosides (ginsenoside 20(R)-Rh2 and ginsenoside 20(S)-Rh2) on prostate cancer cells in vitro. Only ginsenoside 20(S)-Rh2 showed proliferation inhibition on androgen-dependent and -independent prostate cancer cells. These results implied that the stereochemistry of the hydroxyl group at C-20 may play an important role in antitumor activities.     

Antibacterial Activity of Thai Medicinal Plants against Methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen which causes severe morbidity and mortality worldwide. Seventeen Thai medicinal plants were investigated for their activity against MRSA. Garcinia mangostana was identified as the most potent plant, and its activity was traced to the prenylated xanthone, α-mangostin (MIC and MBC values of 1.95 and 3.91 µg/ml, respectively).     

The effects of ganoderma alcohols isolated from Ganoderma lucidum on the androgen receptor binding and the growth of LNCaP cells

The effects of ganoderma alcohols isolated from ethanol extracts of Ganoderma lucidum (Fr.) Krast (Ganodermataceae) on the androgen receptor binding and the growth of LNCaP cells have been investigated. Less than two hydroxyl groups in 17β-side chain are needed for binding to androgen receptor. In the case of the ganoderma alcohols with the same number of hydroxyl groups in 17β-side chain, the one which has C-3 carbonyl group showed better binding activity to androgen receptor than that which has C-3 hydroxyl group. The unsaturation in 17β-side chain is needed for the inhibition of the cell proliferation of androgen-induced LNCaP cells growth.     

Effects of a hexane extract from Laurus novocanariensis leaves on the ethanol metabolism of Wistar rats

A hexane extract from the leaves of Laurus novocanariensis was investigated for its activity on ethanol metabolism in Wistar rats. The extract could interfere with blood ethanol elevation, the induction of gastric alcohol dehydrogenase (ADH) and the reduction of erythrocyte catalase (CAT). The sesquiterpene lactones dehydrocostus lactone and costunolide were identified in the active extract, and might represent its active constituents. These results support the use of L. novocanariensis in the traditional Madeira Island medicine to protect against ethanol injury.     

Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of standardized extracts of Tridax procumbens L.

The standardized EtOAc, MeOH and 70% EtOH extracts of Tridax procumbens aerial parts showed significant inhibition of rat paw edema at a medium dose of 200 mg/kg and the EtOAC extract was the most active. These extracts were standardized by HPLC with the help of chemical markers. Further, the extracts were evaluated for COX-1 and COX-2 inhibitory activity and EtOAc extract exhibited the highest inhibition of COX-1 and COX-2 at 50 μg/mL. Cent aurein, centaureidin and bergenin were isolated as COX-1 and COX-2 inhibitory principles from the EtOAc extract. The extracts also exhibited antioxidant activity against DPPH and ABTS free radicals. The anti-inflammatory activity of T. procumbens aerial parts could be at least in part due to COX-1, COX-2 enzyme inhibition and free radical-scavenging activities which may be attributed to the presence of flavonoids and other polyphenols in the extracts.     

C-glycosyl flavones from Peperomia blanda

The methanol extract from aerial parts of the Peperomia blanda (Piperaceae) yielded two C-glycosyl-flavones. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR, chemical transformation and comparison with the related known compounds. The structure of the new flavonoids were established as 4′-methoxy-vitexin 7-O-β-d-xylopyranoside (1) (7-O-β-d-xylopyranosyl-8-C-β-d-glucopyranosyl-4′-methoxy-apigenin) and vicenin-2 (2). The antioxidant activity of both compounds was investigated using the DPPH assay. Both compounds showed only modest activity, with IC50 values of 357.2 µM for 1, and 90.5 µM for 2.     

Cytotoxic activity of the root extract from Myoschilos oblongum

The crude methanolic root extract of Myoschilos oblongum exhibited a significant cytotoxic activity against PZ-HPV-7 human prostate cells. Furthermore, two esters of docosanol were isolated from the CH(2)Cl(2) extract.     

High performance liquid chromatographic analysis and anticancer potential of Oplopanax horridus: Comparison of stem and berry extracts

Oplopanax horridus or devil's club is a herbal medicine distributed in North America. The constituents and pharmacological activities of O. horridus (OPH) are largely unknown. In this study, we assayed OPH stem and berry extracts using high performance liquid chromatography (HPLC). The anticancer potentials of extracts on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC) were determined by MTS method. The effect of stem extract on cancer cell cycle, expression of cyclin A, and apoptosis were assayed using flow cytometry. HPLC data showed that the composition of OPH stem extract is more complicated than the berry extract. The wavelength of maximum absorption of the major constituent in stem and berry is 196.0 nm and 201.9 nm, respectively. Compared to the berry extract, the stem extract showed significant potent antiproliferative effect on all the studied cell lines. The stem extract at 0.1 mg/ml arrested cancer cells in S- and G2/M-phases, and significantly induced expression of cyclin A. After treatment with 0.1 mg/ml of stem extract for 72 h, apoptotic cells were increased to 45.2%, while control was 9.6%. The cell cycle arrest and induction of apoptosis may play a critical role in cancer chemoprevention by Oplopanax horridus stem extract.     

Antioxidant properties and polyphenol contents of trembling aspen bark extracts

Trembling aspen (Populus tremuloides Michx) bark was extracted with water and the crude extract fractionated with tert-butyl-methyl ether (TBME), ethyl acetate (EtOAc) and n-butanol (BuOH) to obtain four different fractions. The antioxidant properties of the bark hot water extracts and its fractions were determined by three in vitro experiments: DPPH assay, phosphomolybdenum assay and canola oil thermoxidation assay by DSC analysis. Most of the results of the reported tests showed that the crude hot water extract and its fractions exhibited a strong antioxidant activity, higher than the synthetic antioxidant BHT. The results of this study confirm that antioxidant activity is a property that strongly depends on the oxidation conditions used in the particular oxidation test. Among the fractions separated from the aqueous extracts of bark, BuOH, TBME and EtOAc soluble fractions exhibited the best antioxidant efficiency, in phosphomolybdenum assay, DPPH assay and canola oil thermoxidation, respectively. Total phenol, flavonoid and flavanol contents were also evaluated and the results confirmed that the polyphenols contained in the hot water extract of this bark are mainly composed of non-flavonoid compounds.