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.     

Lignans from the heartwood of Streblus asper and their inhibiting activities to hepatitis B virus

Three new lignans, erythro-strebluslignanol (1), threo-7'-methoxyl strebluslignanol (2) and erythro-7'-methoxyl strebluslignanol (3), together with twelve known compounds were isolated from the n-butanol and chloroform fractions of the heartwood of Streblus asper. Their structures were elucidated through extensive spectroscopic methods, including MS and 2D NMR experiments (HMQC and HMBC). The stereochemistry at the chiral center was determined using CD spectra, as well as analysis of coupling constants and optical rotation data, respectively. Primary bioassays showed that 6-hydroxyl-7-methoxyl-coumarin (5) and ursolic acid (10) showed anti-HBV activities, with IC(50) values of 29.60 μM and 89.91 μM for HBsAg at no cytotoxicity, and IC(50) values of 46.41 μM and 97.61 μM for HBeAg at no cytotoxicity, respectively.     

Isoprenoid-substituted flavonoids from wood of Artocarpus heterophyllus on B16 melanoma cells: Cytotoxicity and structural criteria

As a result of cytotoxicity-guided fractionation, nine flavonoids, artocarpin (1), cudraflavone C (2), 6-prenylapigenin (3), kuwanon C (4), norartocarpin (5), albanin A (6), cudraflavone B (7), brosimone I (8) and artocarpanone (9) were identified from the methanol extract of the wood of Artocarpus heterophyllus, known commonly as Nangka in Indonesia. A structure–activity investigation of the effect of these isolated compounds (1–9) and structurally related compounds on B16 melanoma cells indicated that isoprenoid moiety substitutions in flavonoids enhance their cytotoxicity, and that the position of attachment and the number of isoprenoid-substituent moieties per molecule influence flavonoid cytotoxicity.     

Effects of the exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis on immunocytes of H22 tumor bearing mice

In order to explore the effects of exopolysaccharide fraction (EPSF) from one of the anamorph strains of Cordyceps sinensis on immunocyte activity of H22 tumor bearing mice, ICR mice were treated with EPSF for 7 days by intraperitoneal injection at doses of 15 mg/kg (low-dose), 30 mg/kg (mid-dose) and 60 mg/kg (high-dose) after H22 tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Phagocytosis of mouse peritoneal macrophages was tested by neutral red uptake. The TNF-alpha expression of macrophages was assayed by ELISA. Proliferation ability and cytotoxicity of spleen lymphocytes were determined by MTT methods. The mRNA levels of cytokine TNF-alpha and IFN-gamma mRNA of spleen lymphocytes were detected by RT-PCR. The results indicated that EPSF not only significantly inhibited the H22 tumor growth, but also significantly elevated immunocytes' activity. It significantly enhanced the phagocytosis capacity of peritoneal macrophages and proliferation ability of spleen lymphocytes at all the three doses; it significantly promoted macrophages' TNF-alpha expression and spleen lymphocytes' cytotoxicity. EPSF also significantly elevated TNF-alpha and IFN-gamma mRNA expression of splenic lymphocytes. This experimental finding suggests that EPSF could elevate the immunocytes' activity in H22 tumor bearing mice.     

Anti-HBV activities of Streblus asper and constituents of its roots

The extracts from leaves, heartwood, barks and roots of the Streblus asper were investigated for anti-HBV activities, separately. The results suggested that the MeOH extracts of the heartwood, barks, and roots exhibited good anti-HBV activities. Further investigations displayed that ethyl acetate and n-butanol soluble parts of their MeOH extracts showed more significant anti-HBV activities. Moreover, a new lignan, together with 11 known compounds, was isolated from n-butanol-soluble part of MeOH extract of the roots of S. asper. The structures were elucidated by spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC) and HR-EI-MS experiments. Compounds 1-3 were evaluated for their anti-HBV activities. Honokiol showed significant anti-HBV activity with IC(50) values of 3.14μM and 4.74μM for HBsAg and HBeAg with no cytotoxicity respectively, while lamivudine (3TC, positive control) exhibited weak anti-HBV activity with IC(50) values of 11.81μM and 25.80μM for HBsAg and HBeAg respectively.     

A new dimeric aporphine from the roots of Artabotrys spinosus

A new dimeric aporphine, artabotrysine along with five known compounds was isolated from the roots of Artabotrys spinosus. Their structures were fully established on the basis of spectral evidence. All isolated compounds were evaluated for their cytotoxicity on HeLa and KB cells.     

Solanum incanum and S. heteracanthum as sources of biologically active steroid glycosides: confirmation of their synonymy

A new spirostanol saponin (1), along with four known saponins, dioscin (2), protodioscin (3), methyl-protodioscin (4), and indioside D (5), and one known steroid glycoalkaloid solamargine (6) were isolated from the two synonymous species, Solanum incanum and S. heteracanthum. The structure of the new saponin was established as (23S,25R)-spirost-5-en-3β,23-diol 3-O-{β-D-xylopyranosyl-(1→2)-O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside}, by using a combination of 1D and 2D NMR techniques including (1)H, (13)C, COSY, TOCSY, NOESY, HSQC and HMBC experiments and by mass spectrometry. The compounds 1, 3, 4 and 5 were evaluated for cytotoxicity against five cancer cell lines and for antioxidant and cytoprotective activity.     

A new quinazolinedione alkaloid from the fruits of Evodia officinalis

A new quinazolinedione alkaloid, wuchuyuamide IV (1) was isolated from the fruits of Evodia officinalis.1 showed moderate cytotoxicity against Hela and HT1080 cell lines.     

Asterosaponins from the starfish Culcita novaeguineae and their bioactivities

Bioassay-guided fractionation of the n-BuOH extract of the starfish Culcita novaeguineae resulted in the isolation of one new sulfated steroidal glycoside (asterosaponin) (1), along with three known asterosaponins, thornasteroside A (2), marthasteroside A(1) (3) and regularoside A (4), as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Their structures were elucidated by extensive spectral studies and chemical evidences. All the saponins showed moderate cytotoxicity against cancer cell lines K-562 and BEL-7402.     

Macrostachyols A-D, new oligostilbenoids from the roots of Gnetum macrostachyum

Four new oligostilbenes, macrostachyols A-D (1-4) along with six known stilbenoids (5-10), were isolated from the roots of Gnetum macrostachyum. These compounds were also evaluated for their cytotoxicity towards HeLa and KB cell lines. Only compound 4 showed the significant cytotoxicity to HeLa cells with IC₅₀ value of 4.13 μM.     

A new dimeric resveratrol from the roots of Shorea roxburghii

A new resveratrol dimer, roxburghiol A (1) together with eleven known compounds were isolated from the roots of Shorea roxburghii. Their structures were identified on the basis of spectroscopic evidence and physicochemical properties. All isolated compounds were evaluated for their cytotoxicity (KB and HeLa cells). Compounds 8 and 9 showed potent cytotoxicity against both KB and HeLa cell lines with IC₅₀ values of 6.5, 8.5 and 8.7, 10.1 μg/mL, respectively.     

Geraniin and amariin,ellagitannins from Phyllanthus amarus, protect liver cells against ethanol induced cytotoxicity

Ethanol mediated free radical generation plays an important role in the pathogenesis of liver injuries and alcoholic liver diseases. In the present study two ellagitannins namely geraniin and amariin isolated from Phyllanthus amarus were examined for their ability to protect mouse liver slices against ethanol induced toxicity and possible mechanism of its protection. Oxidative stress markers such as, lipid peroxidation, protein carbonyl formation, amount of 8-hydroxy-2-deoxyguanosine and antioxidant enzymes levels were measured using specific biochemical assays. Poly (ADP-ribose) polymerase (PARP), Bax and Bcl2 were checked to assess the induction of apoptosis using western blots. The results showed that geraniin and amariin protected mouse liver slices against ethanol induced cytotoxicity. Both compounds inhibited oxidation of lipid, protein and formation of 8-hydroxy-2-deoxyguanosine, all of which were found to be elevated on exposure to ethanol. These compounds restored the antioxidant enzymes altered on ethanol exposure. Compounds also inhibited the cleavage of PARP and bax and restored Bcl2, induced on exposure to ethanol. In summary, both ellagitannins effectively protected mouse liver slices against ethanol induced cytotoxicity and apoptosis by reducing oxidative damage to biological molecules and modulating Bax/Bcl-2 ratio respectively, thus minimizing liver injury.     

Two new cytotoxic isomeric indole alkaloids from the roots of Nauclea orientalis

A pair of new isomeric indole alkaloids, naucleaorals A (1) and B (2) were isolated from the roots of Nauclea orientalis. The structures of compounds 1 and 2 were fully characterized using spectroscopic data, and were tested for their cytotoxicity (HeLa and KB cells) and antimalarial activity. Compound 1 showed significant cytotoxicity to HeLa cells with an IC₅₀ value of 4.0 µg/mL, while compound 2 exhibited very modest cytotoxicity to both cell lines with IC₅₀ values of 7.8 and 9.5 µg/mL, respectively. Both compounds proved to be inactive in antimalarial assays (IC₅₀ > 10.00 µg/mL).     

Tabebuialdehydes A–C,cyclopentene dialdehyde derivatives from the roots of Tabebuia rosea

Two new cyclopentene dialdehydes, tabebuialdehydes A and B (1 and 2) and a new dihydrocyclopenta[c]furan monoaldehyde, tabebuialdehyde C (3), along with ten known compounds were isolated from the roots of Tabebuia rosea. The structures of all isolated compounds were elucidated through their physical properties and by the use of spectroscopic methods, as well as comparisons with previous literature data. Moreover, all isolated compounds were evaluated for their cytotoxicity (KB and HeLa cell lines). Compounds 6, 7 and 9 showed significant cytotoxicity against both KB and HeLa cells with IC₅₀ values of 1.35 and 1.15, 0.53 and 0.77, 1.79 and 0.73 μg/mL, respectively.     

A new coumarin from Sarcandra glabra

Sarcandracoumarin (1), the first coumarin having a 1-phenylethyl substituent at the C-3 position, was isolated along with eleven known phenolic compounds from the water extract of Sarcandra glabra. Its structure was elucidated on the basis of spectroscopic data. Compound 1 exhibited moderate or weak cytotoxicity against several tumor cell lines.     

Cytotoxic triterpene glycosides from the sea cucumber Pseudocolochirus violaceus

A new triterpene glycoside (1) along with the known intercedenside B (2) was isolated from the sea cucumber Pseudocolochirus violaceus. Glycoside 1 was elucidated as 3-O-{6-O-sodiumsulfate-3-O-methyl-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-xylopyranosyl(1-->2)]-beta-D-quinovopyranosyl-(1-->2)-4-O-sodiumsulfate-beta-D-xylopyranosyl}-16beta-acetoxy-holosta-7, 24-diene-3beta-ol on the basis of extensive spectral studies and chemical evidence. Both the glycosides exhibited significant cytotoxicity against cancer cell lines MKN-45 and HCT-116.     

Diarylheptanoids from the rhizomes of Alpinia officinarum and their anticancer activity

Two new diarylheptanoids (1, 2), together with two known analogs (3, 4), were isolated from the rhizomes of Alpinia officinarum. The new compounds were elucidated to be (5S)-5-hydroxy-7-(3, 4-dihydroxyphenyl)-1-phenyl-3-heptanone (1) and (5R)-5-hydroxy-7-(3-methoxy-4, 5-dihydroxyphenyl)-1-phenyl-3-heptanone (2) based on their spectral analysis. Compound 4 showed moderate cytotoxicity against human tumor cell lines, HepG2, MCF-7 and SF-268, while no significant effect were found for compounds 1-3.     

A cytotoxic triterpenoid saponin from under-ground parts of Gypsophila pilulifera Boiss.& Heldr

A cytotoxic triterpenoid saponin was isolated from the under-ground parts of Gypsophila pilulifera Boiss.& Heldr. (Caryophyllaceae) naturally grow in the southwestern region of the Turkey. The structures of saponin was elucidated as 3-O-β-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosyl quillaic acid 28-O-β-D-glucopyranosyl-(1→3)-[β-d-xylopyranosyl-(1→4]-α-l-rhamnopyranosyl-(1→2)-β-D-fucopyranosyl ester on the basis of extensive spectral analysis and chemical evidence. The separated triterpenoid saponin was isolated from Gypsophila pilulifera for the first time. The saponin compound displayed significant cytotoxicity against A549 cell line with IC(50) values >16μM.     

Five new furostanol saponins from the rhizomes of Tupistra chinensis

Five new furostanol saponins (1-5), together with three known compounds (6-8) were obtained from the n-butanol soluble fraction of ethanol extract from Tupistra chinensis. Their structures were determined on the basis of chemical methods and spectral data. The isolated compounds were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, compounds 6, 7, and 8 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 6.6, 6.7 and 29.1 μM, respectively.     

A new cytotoxic 1-azaanthraquinone from the stems of Goniothalamus laoticus

A new 1-azaanthraquinone, named laoticuzanone A (1), and a synthetically known 3-methyl-1H-1-azaanthracene-2,9,10-trione (2), together with four known compounds, Griffithazanone A (3), methyl sinapate (4), methyl p-coumarate (5), and p-hydroxyphenylethyl p-coumarate (6) were isolated from the stems of Goniothalamus laoticus. Their structures were established on the basis of spectroscopic data as well as comparisons with the previous literature data. Compound 1 showed the highest cytotoxicity against KB and HeLa cells with IC₅₀ values of 0.68 and 0.50 μg/ml, respectively.