Cycloartane triterpenoids and their glycosides from the rhizomes of Cimicifuga foetida.

A phytochemical study on the rhizomes of Cimicifuga foetida resulted in the isolation of two new cycloartane triterpenoids (1 and 2), eight new cycloartane glycosides (3-10), and six known cycloartane glycoside analogues (11-16). The structures of 1-10 were determined by application of spectroscopic methods, with the absolute configuration of 1 determined by X-ray crystallography. Compounds 1-6, as three pairs of epimers at C-10 and C-24, belong to a seven-membered-ring variant of 9,10-seco-9,19-cycloartane triterpenoids, and glycosides 3-10 were found to be 3-O-ß-D-xylopyranosides. The cytotoxicity of the isolates was evaluated against five selected human tumor cell lines, and the known compounds 15 and 16 showed cytotoxicity against the hepatocellular carcinoma SMMC-7721 cell line with IC50 values of 5.5 and 6.3 µM, respectively.

Cardioprotective Effects of 20(S)-Ginsenoside Rh2 against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin (DOX) is considered as one of the best antineoplastic agents. However, its clinical use is restricted by its associated cardiotoxicity, which is mediated by the production of reactive oxygen species. In this study, 20(S)-ginsenoside Rh2 (Rh2) was explored whether it had protective effects against DOX-induced cardiotoxicity. In vitro study on H9C2 cell line, as well as in vivo investigation in one mouse and one rat model of DOX-induced cardiomyopathy, was carried out. The results showed that pretreatment with Rh2 significantly increased the viability of DOX-injured H9C2 cells. In the mouse model, Rh2 could suppress the DOX-induced release of the cardiac enzymes into serum and improved the occurred pathological changes through ameliorating the decreased antioxidant biomolecules and the cumulated lipid peroxidation malondialdehyde in heart tissues. In the rat model, Rh2 could attenuate the change of ECG resulting from DOX administration. Furthermore, Rh2 enhanced the antitumor activity of DOX in A549 cells. Our findings thus demonstrated that Rh2 pretreatment could effectively alleviate heart injury induced by DOX, and Rh2 might act as a novel protective agent in the clinical usefulness of DOX.

Cytotoxic constituents from the skin of the toad Bufo bufo gargarizans.

To study the chemical composition of the skin of Bufo bufo gargarizans, various chromatographic methods were used in the isolation procedures and the structures of isolated compounds were determined based on NMR and MS analysis. As a result, two new compounds were isolated from its ethanolic extract and characterized as N-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-N-methylurea (1) and 19-oxocinobufotalin 3-adipoylarginine ester (2), together with 11 known compounds. Isolated bufadienolides showed significant inhibition effect against human hepatocellular carcinoma cell line SMMC-7721 in vitro.

Studies on cytotoxic constituents from the skin of the toad Bufo bufo gargarizans.

To study the chemical composition of the skin of Bufo bufo gargarizans, many kinds of chromatography methods were used in the isolation procedures, while the structures of isolated compounds were determined on the basis of their NMR and MS spectral analysis. As a result, two new compounds were isolated from its ethanolic extract and characterized as cinobufotalin 3-nonanedioylarginine ester (8) and bufotalin 3-pimeloylarginine ester (14). Furthermore, 13 known compounds were obtained. Isolated bufadienolides showed significant inhibition effect against SMMC-7721 cell lines in vitro.

Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-alpha release in LPS-activated macrophages.

Nitric oxide (NO), derived from L-arginine, is produced by two types (constitutive and inducible) of nitric oxide synthase (NOS: cNOS and iNOS). The NO produced in large amounts by the iNOS is known to be responsible for inflammation, the vasodilation, and hypotension observed in septic shock and cancer metastasis. The inhibitors of the overproduction of NO, thus, may be useful candidates for the treatment of inflammatory diseases. We have found that the petroleum ether extract of Saussurea lappa Decne, which is a wild species wildly distributed in India, can strongly inhibit the overproduction of NO in mouse macrophage RAW 264.7 cells. Through bioassay-guided fractionation, 13 sesquiterpenes were isolated from the active petroleum ether extract. Furthermore, another five sesquiterpenes were synthesized by chemical methods. In the present study, their effects on LPS-induced NO production and TNF-alpha release are reported. Compounds 1, 3, 9, 17, and 18 showed significant inhibitory activities on the production of NO and release of TNF-alpha with IC(50) values lower than 1 micromol/l. SAR studies suggest that the exocyclic double bond (Delta(11(13))) is necessary for the inhibitory activities of sesquiterpenes on the NO production.

[Chemical constituents from dried sorophore of cultured Cordyceps militaris].

OBJECTIVE: To investigate the chemical constituents of the dried sorophore of cultured Cordyceps militaris. METHOD: Compounds were isolated and purified by macroporous adsorption resin and silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical properties and spectral data (IR, FAB-MS, 1H-NMR and 13C-NMR). RESULT: Nine compounds were isolated and identified as: ergosta-4, 6, 8 (14)-tetraen-3-one (1), citrostadienol (2), tetracosanoic acid 2, 3-dihydroxypropyl ester (3), ergosterol (4), ergosterol peroxide (5), ergosta-7, 22-dien-3beta, 5alpha, 6beta-triol (6), cordycepin (7), adenosine (8), N-(2-hydroxyethyl) adenosine (9), respectively. CONCLUSION: Compounds 1-3, 6, 9 were separated from the sorophore of cultured C. militaris for the first time.

neo-Clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

Three neo-clerodane diterpenoids, named barbatins A-C (1-3), and the neo-clerodane diterpenoid nicotinyl ester, named scutebarbatine B (4), were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic analyses (UV, IR, HRFAB-MS, 1D NMR and 2D NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, with IC50 values in the range 3.5-8.1 microM.

Four new neo-clerodane diterpenoid alkaloids from Scutellaria barbata with cytotoxic activities.

Four new neo-clerodane diterpenoid alkaloids, named scutebarbatines C-F (1-4), were isolated from the whole plants of Scutellaria barbata D. DON. Their structures were elucidated by spectral analyses (UV, IR, FAB-MS, 1D-NMR and 2D-NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer cell lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and gave IC(50) values in the range 3.9-7.8 muM.

[Alkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium].

AIM: To study the alkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium L. METHODS: Isolation and purification were carried out on silica gel and HPLC; the structures of chemical constituents were elucidated by spectral analysis. RESULTS: From the alkaline-degradation products, nine compounds were identified as: 20 (S) -protopanaxadiol (I), 20 (S) -dammar-25 (26)-ene-3beta, 12beta, 20-triol (II), 24 (R) -ocotillol (III), 20 (S) -protopanaxatriol (IV), 20 (S) -dammar-25 (26)-ene-3beta, 6alpha, 12beta, 20-tetrol (V), dammar-20 (21), 24-diene-3beta, 12beta-diol (VI), dammar-20(21), 24-diene-3beta, 6alpha, 12beta-triol (VII), 20 (S), 24 (S) -dammar-25 (26) -ene-3beta, 6alpha, 12beta, 20, 24-pentanol (VIII), 20 (S) -dammar-23-ene-25-hydroperoxyl-3beta, 6alpha, 12beta, 20-tetrol (IX). CONCLUSION: The configuration of C20 position of ginsenosides was not changed by alkaline-degradation. The complete assignments of 1H and 13C NMR chemical shifts of four new compounds V, VII, VIII, IX, were acquired by means of 2D NMR spectra. Compound I showed antitumor effect on human colon carcinoma cells in vitro.