Water-soluble glycosides from Ruta graveolens.

An EtOH extract of the dried aerial parts of Ruta graveolens was suspended in water and then partitioned with EtOAc. Three new glycosides, 3'-sinapoyl-6-feruloylsucrose (4), methylcnidioside A (5), and methylpicraquassioside A (6), together with four known glycosides, 3',6-disinapoylsucrose (1), cnidioside A (2), rutin, and picraquassioside A (3), were isolated from the water-soluble part. Their structures were elucidated by interpretation of IR, MS, and 1D and 2D NMR spectra and comparison with literature data.

Blocking of cell proliferation, cytokines production and genes expression following administration of Chinese herbs in the human mesangial cells.

In the hope of identifying agents of therapeutic value in immuoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cell proliferation. The results indicated that 4 out of the 15 crude extracts inhibited human cells proliferation activated by IL-1beta and IL-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Ludwiga octovalvis (MLS-052), 49.9 +/- 1.8; Rhus semialata (MLS-053), 31.2 +/- 1.6; Tabernaemontana divaricata (MLS-054), 50.0 +/- 2.1; Amepelopsis brevipedunculata (MLS-059), 42.9 +/- 1.1. These findings indicate that human mesangial cells were most sensitive to MLS-053 treatment. These herbs also decreased interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production. Moreover, IL- 1beta mRNA expression was inhibited by Rhus semialata (R. semialata; MLS-053). It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.

Inhibition of low density lipoprotein oxidation by tetrahydrofurofuran lignans from Forsythia suspensa and Magnolia coco.

Based on the inhibition of Cu(2+)-induced LDL oxidation as marker, the major antioxidants in the fruits of Forsythia suspensa and the stems of Magnolia coco were identified. Of these bioactive tetrahydrofurofuran lignans, pinoresinol, phillygenin, and syringaresinol were more potent than probucol. Sesamin and fargesin, which do not contain phenol groups, were found much less active.

Cytotoxicity of curcuminoids and some novel compounds from Curcuma zedoaria.

Bioassay-directed fractionation of an EtOH extract of Curcuma zedoaria led to isolation of an active curcuminoid, which was identified as demethoxycurcumin (2) by comparison of its 1H and 13C NMR spectra with literature data and by direct comparison with synthetic material. Curcumin (1) and bisdemethoxycurcumin (3) were also obtained. Curcuminoids (1-3) were synthesized and demonstrated to be cytotoxic against human ovarian cancer OVCAR-3 cells. The observed CD50 values of 1, 2, and 3 were 4.4, 3.8, and 3.1 microg/mL, respectively. Three additional novel compounds, 3, 7-dimethylindan-5-carboxylic acid (4), curcolonol (5), and guaidiol (6), were also isolated from the EtOH extract. The structures and relative stereochemistry of 4-6 were determined by spectroscopic methods and X-ray crystallographic analysis.

Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies.

In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.

Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla.

d-Dicentrine, a naturally occurring aporphine type isoquinoline alkaloid, isolated from the root of Lindera megaphylla Hemsl. (Lauraceae), was evaluated for its potential anti-cancer activity. We found d-dicentrine significantly inhibited the growth of human hepatoma cell line HuH-7 by delaying its doubling time in tissue culture. An in vitro colony forming assay showed that d-dicentrine decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and MS-G2, used in our study. Biosyntheses of the macromolecules DNA and RNA were also strongly inhibited. An MTT assay in 21 tumor cell lines also revealed that d-dicentrine was most cytotoxic to esophageal carcinoma HCE-6, lymphoma cell lines Molt-4 and CESS, leukemia cell lines HL60 and K562, and hepatoma cell line MS-G2. An in vitro tumor growing assay in the Severe Combined immunodeficiency (SCID) mice showed that intraperitoneal injection of d-dicentrine at the dose of 100 micrograms twice a week for 4 weeks significantly inhibited the tumor incidence of leukemia cell line K562 in SCID mice. All these data indicated that d-dicentrine has potential anti-tumor applications.

Selective cytotoxicity of ginkgetin from Selaginella moellendorffii.

Bioassay-directed fractionation of an ethanolic extract of Selaginella moellendorffii has led to the isolation of a known biflavone, ginkgetin (1). A dose-dependent inhibition was observed with 1 on the growth of OVCAR-3 (human ovarian adenocarcinoma) cells with 50% inhibition occurring at 1.8 micrograms/mL. Nonbioactive fractions yielded four additional known biflavones, amentoflavone 7,4',7",4"'-tetramethyl ether, kayaflavone, podocarpusflavone A, and amentoflavone.

A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi.

Polygonum hypoleucum Ohwi (P. hypoleucum Ohwi) has been used as a Chinese medicine for a long time. In the present study, four anthraquinones, emodin, emodin 1-O-beta-D-glucoside (49A), physcion (62A), and physcion 1-O-beta-D-glucoside (50A) were identified from P. hypoleucum Ohwi and their inhibitory effects on various tumor cells proliferation were investigated. On a percentage basis, emodin had the highest suppressing activity on the various tumor cells proliferation. At 10 microg/ml, the percentage inhibition on K562 cells proliferation for emodin, 49A, 62A, and 50A were 97+/-3.4%, 18+7.3%, 24+/-3.6%, and 31+/-8.9%, respectively. However, inhibitory activities of 10 microg/ml of emodin, 49A, 62A, or 50A on Raji cells proliferation were 98+/-5.0%, 25+/-5.0%, 22+/-3.2%, and 28+/-4.3%, respectively. It was also found that the both C1 and C3 positions of emodin were important for antitumor action. The IC50s of emodin, 49A, 62A, and 50A on various tumor cells were also calculated. The IC50 of emodin on K562 cells was significantly lower than on Raji, HeLa, Calu-1, Wish, and Vero cells (1.5+/-0.2 vs. 2.8+/-0.4 microg/ml, P < 0.01 ;1.5+/-0.2 vs. 8.4+/-1.6 microg/ml; 1.5+/-0.2 vs. 8.9+/-1.0 microg/ml; 1.5+/-0.2 vs. 8.7+/-0.5 microg/ml; 1.5/-0.2 vs. 3.5+/-0.12 microg/ml; P < 0.001). The results indicated that K562 and Raji cells were more sensitive to emodin treatment. Cell viability test indicated that inhibitory effect of emodin on various tumor cell lines was not through direct cytotoxicity. It suggested P. hypoleucum Ohwi included a tumor cell growth inhibitor.

Antiplatelet arylnaphthalide lignans from Justicia procumbens.

Fractionation of the EtOH extract of Justicia procumbens, guided by antiplatelet bioassay, led to the isolation of nine known arylnaphthalide lignans, neojusticin A (1), justicidin B (2), justicidin A (3), taiwanin E methyl ether (4), neojusticin B (5), chinensinaphthol methyl ether (6), taiwanin E (8), chinensinaphthol (9), and diphyllin (10), and a new arylnaphthalide lignan that was characterized by spectral means as 4'-demethylchinensinaphthol methyl ether (7). Compounds 1, 2, 4, and 8 significantly inhibited platelet aggregation.

Two rare alkaloids from Pratia nummularia.

Two rare alkaloids, 1-(2-,N-methylpiperidyl)-butan-2-one (1) and l-(2-N-methylpiperidyl)-pentan-2-one (2), were identified from the medicinal plant Pratia nummularia. The structure of 1 was elucidated by means of spectroscopic methods. Compound 2 was established by spectral comparison with synthetic material.

Constituents and cytotoxic principles of Nothapodytes foetida.

A new naturally occurring alkaloid, acetylcamptothecin, together with 17 known compounds, (+)-1-hydroxypinoresinol, omega-hydroxypropioguaiacone, p-hydroxybenzaldehyde, scopoletin, uracil, thymine, sitosterol, sitosteryl-beta-D-glucoside, 3 beta-hydroxy-stigmast-5-en-7-one, stigmast-5-en-3 beta,7 alpha-diol, 6 beta-hydroxystigmast-4-en-3-one, sitost-4-en-3-one, linoleic acid, trigonelline, camptothecin, 9-O-methoxycamptothecin and pumiloside were isolated and characterized from the stem of Nothapodytes foetida. Among them, scopoletin, camptothecin, 9-O-methoxycamptothecin and O-acetylcamptothecin showed significant cytotoxic activity.

Bioactive principles from the roots of Lindera megaphylla.

d-Dicentrine was isolated from the root of Lindera megaphylla. It inhibited the aggregation of washed rabbit platelets induced by ADP, collagen, arachidonic acid, and PAF. It also inhibited the high potassium- and norepinephrine-induced contraction of rat thoracic aorta. In rat ventricular cells treated with 3 microM d-dicentrine, the action potential duration (ADP50) was prolonged from 59.9 +/- 11.3 msec to 201 +/- 28.7 msec.