A new cardenolide glycoside from the roots of Streptocaulon juventas (lour.) merr. (Asclepiadaceae).

From remaining aqueous fraction of the roots of Streptocaulon juventas, one new cardiac glycoside named periplogenin 3-O-ß-gentiobioside (1) together with six known ones (2-7) were isolated. Their relative structures were elucidated based on NMR spectroscopic analysis. Compound 1 showed moderate cytotoxicity against non-small cell lung carcinoma NCI-H460 and ovarian cancer HeLa cells. Moreover, compounds 2 and 3 exhibited remarkable cytotoxicity against NCI-H460 cell with the IC50 values of 0.34 and 0.068 µM, respectively.

Two new meroterpenoids from the aerial parts of Ampelopsis cantoniensis (Vitaceae).

From EtOAc-soluble fraction of the aerial parts of Ampelopsis cantoniensis (Vitaceae), two new meroterpenoids named ampechromonol A (1) and ampechromonol B (2), together with five known compounds (3-7), were isolated. Their structures were elucidated based on NMR spectroscopic analysis. The plausible biosynthesis pathway for the formation of two new meroterpenoids was proposed. This research is the first isolation of meroterpenoids from Ampelopsis genus. Compounds 1 and 2 showed weak cytotoxicity against MCF-7 breast cancer cells.

Nimbandiolactone-21 and nimbandioloxyfuran, two new 28-norlimonoids from the leaves of Azadirachta indica (Meliaceae).

From an EtOAc-soluble fraction of the leaves of Azadirachta indica, two new 28-norlimonoids named nimbandiolactone-21 (1) and nimbandioloxyfuran (2), together with nimbandiolactone-23 (3), were isolated. Their relative structures were elucidated based on NMR spectroscopic interpretation and biosynthetic consideration. Nimbandioloxyfuran (2) and nimbandiolactone-23 (3) showed potent α-glucosidase inhibitory activity, with the IC50 values of 46.2 and 38.7 µM, respectively.

Xanthine oxidase inhibitors from the flowers of Chrysanthemum sinense.

From the MeOH extract of the flowers of Chrysanthemum sinense, a new flavone glucoside, acacetin 7- O-(3- O-acetyl- beta- D-glucopyranoside), has been isolated together with 27 known compounds including flavonoids, caffeoylquinic acid derivatives, phenolics, and a monoterpenoid glucoside. Their structures were elucidated on the basis of spectroscopic data. Compounds and displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compounds and showed more potent inhibitory activity, with IC50 values ranging from 0.13 to 2.31 microM, than that of a positive control allopurinol (IC50=2.50 microM). The kinetic study indicated that and displayed competitive-type inhibition like that of allopurinol, while displayed a mixed-type inhibition.

Hypouricemic effects of acacetin and 4,5-o-dicaffeoylquinic acid methyl ester on serum uric acid levels in potassium oxonate-pretreated rats.

The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC(50) values of 2.22 muM and 5.27 muM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.

Xanthine oxidase inhibitors from the heartwood of Vietnamese Caesalpinia sappan.

From the MeOH extract of Vietnamese Caesalpinia sappan, a novel biogenetically exclusive benzindenopyran, with a new carbon framework, neoprotosappanin (1), and a new compound, protosappanin A dimethyl acetal (3), were isolated together with protosappanin E-2 (2), neosappanone A (4), and 13 previously reported phenolic compounds (5-17). Their structures were elucidated on the basis of spectroscopic data. Compounds 1-4, 7, 13, and 15-17 showed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and sappanchalcone (17) showed the most potent activity with an IC50 value of 3.9 microM, comparable to that of positive control allopurinol (IC50, 2.5 microM). The kinetic study of these inhibitors indicated that they are competitive inhibitors, the same as allopurinol, except for 1 and 16 which are noncompetitive inhibitors.

Xanthine oxidase inhibitory activity of Vietnamese medicinal plants.

Among 288 extracts, prepared from 96 medicinal plants used in Vietnamese traditional medicine to treat gout and related symptoms, 188 demonstrated xanthine oxidase (XO) inhibitory activity at 100 microg/ml, with 46 having greater than 50% inhibition. At 50 microg/ml, 168 of the extracts were active, with 21 possessing more than 50% inhibition. At 25 microg/ml, 146 extracts exhibited inhibitory activity, with 8 showing over 50% inhibition, while 126 extracts presented activity at 10 microg/ml, with 2 having greater than 50% inhibition. The MeOH extracts of Artemisia vulgaris, Caesalpinia sappan (collected at the Seven-Mountain area), Blumea balsamifera (collected in Lam Dong province), Chrysanthemum sinense and MeOH-H(2)O extract of Tetracera scandens (Khanh Hoa province) exhibited strong XO inhibitory activity with IC(50) values less than 20 microg/ml. The most active extract was the MeOH extract of the flower of C. sinense with an IC(50) value of 5.1 microg/ml. Activity-guided fractionation of the MeOH extract led to the isolation of caffeic acid (1), luteolin (2), eriodictyol (3), and 1,5-di-O-caffeoylquinic acid (4). All these compounds showed significant XO inhibitory activity in a concentration-dependent manner, and the activity of 2 was more potent (IC(50) 1.3 microM) than the clinically used drug, allopurinol (IC(50) 2.5 microM).

Antiosteoporotic activity of the water extract of Dioscorea spongiosa.

After 60 MeOH and water extracts of natural crude drugs were screened for their ability to stimulate osteoblast proliferation, four MeOH extracts (Cynomorium songaricum, Drynaria fortunei, Lycium chinense, Rehmannia glutinosa) and seven water extracts (Cornus officinalis, Dendrobium nobile, Dioscorea spongiosa, Drynaria fortunei, Eucommia ulmoides, Lycium chinensis, Viscum coloratum) showed that potent activities were evaluated for inhibition of osteoclast formation. The results indicated that the water extract of D. spongiosa not only showed the strongest stimulation of osteoblast proliferation but also possessed potent inhibitory activity aganist osteoclast formation, whereas it showed lower cytotoxicity in osteoblast and bone marrow cells. A further in vivo experiment determined the antiosteoporotic activity of this extract, in which it inhibited the decrease in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in ovariectomized rats.

Constituents of the Vietnamese medicinal plant Streptocaulon juventas and their antiproliferative activity against the human HT-1080 fibrosarcoma cell line.

The methanolic extract of roots of Streptocaulon juventas, having shown strong antiproliferative activity against the highly metastatic human HT-1080 fibrosarcoma cell line, was subjected to activity-guided isolation to yield 16 cardenolides including five new ones, acovenosigenin A 3-O-beta-digitoxopyranoside (1), digitoxigenin gentiobioside (2), digitoxigenin 3-O-[O-beta-glucopyranosyl-(1-->6)-O-beta-glucopyranosyl-(1-->4)-3-O-acetyl-beta-digitoxopyranoside] (3), digitoxigenin 3-O-[O-beta-glucopyranosyl-(1-->6)-O-beta-glucopyranosyl-(1-->4)-O-beta-digitalopyranosyl-(1-->4)-beta-cymaropyranoside] (4), and periplogenin 3-O-(4-O-beta-glucopyranosyl-beta-digitalopyranoside) (5), and two new hemiterpenoids, (4R)-4-hydroxy-3-isopropylpentyl beta-rutinoside (6) and (R)-2-ethyl-3-methylbutyl beta-rutinoside (7), together with two known phenylpropanoids and a known phenylethanoid. The isolated cardenolides strongly inhibited the proliferation of the HT-1080 cell line (IC(50) values, 54-1600 nM).

Antiproliferative activity of cardenolides isolated from Streptocaulon juventas.

Sixteen cardenolides, two hemiterpenoids, two phenylpropanoids and a phenylethanoid isolated from the roots of Streptocaulon juventas (LOUR.) MERR. were examined for their antiproliferative activity toward three human-derived (HT-1080 fibrosarcoma, lung A549 adenocarcinoma, cervix HeLa adenocarcinoma) and three murine-derived (colon 26-L5 carcinoma, Lewis lung carcinoma, B16-BL6 melanoma) cell lines. The cardenolides selectively and strongly inhibited proliferation of the HT-1080 (IC(50) values, 0.054-1.6 microM) and A549 (IC(50), 0.016-0.65 microM) cell lines. The characteristic morphological changes and ladder-like DNA fragmentation in those cells treated with the cardenolides indicated the antiproliferative activity was due to the induction of apoptosis.

Wild ginseng grows in Myanmar.

Ginseng, the underground parts of plants of Panax species, has been used in oriental traditional medicine for centuries. Unfortunately, because of extensive exploitation over thousands of years, the natural source of these species has been almost exhausted. Recently, we have found a wild ginseng growing in Myanmar. Here, by a combination of chemical composition study and gene sequence analysis, we unambiguously demonstrate that the wild ginseng is actually P. zingiberensis, commonly known as ginger ginseng. This ginseng was an indigenous to the southwestern China. However, now it is seriously threatened to brink of extinction and is put on the highest level of protection in China. Therefore, an appropriate protection measure is highly recommended to preserve this valuable resource, since this Myanmar ginseng might turn out to be the last P. zingiberensis, which could ever be seen in the planet.

Steroidal glycosides from the rhizomes of Dioscorea spongiosa.

A water extract of the rhizomes of Dioscorea spongiosa, which showed antiosteoporotic activity, was examined, and four new pregnane glycosides, named spongipregnolosides A-D (1-4), and two new cholestane glycosides, named spongiosides A (5) and B (6), were isolated together with 15 known glycosides. Their structures were determined on the basis of spectroscopic analysis and chemical methods. Among the isolated compounds, spongioside A (5), hypoglaucin G (7), methylprotodioscin (8), and (R)-oct-1-en-3-yl O-alpha-l-arabinopyranosyl-(1-->6)-alpha-d-glucopyranoside (9) showed potent inhibition against bone resorption induced by parathyroid hormone in a bone organ culture system.

In vitro antiplasmodial activity of antimalarial medicinal plants used in Vietnamese traditional medicine.

Among 42 extracts, prepared from 14 medicinal plants used in Vietnamese traditional medicine to treat malaria, 24 were found to have antiplasmodial activity by inhibiting the growth of the chloroquine-resistant Plasmodium falciparum strain FCR-3 with EC(50) values less than 10 microg/ml. Each medicinal plant possessed at least one active extract. The methanol extract of Coscinium fenestratum had the strongest antiplasmodial activity with EC(50) value of 0.5 microg/ml. Activity-guided fractionation led to identification of berberine as the major active constituent.

Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model.

The effects of berberine in senescence accelerated mice P6 (SAMP6) were investigated to learn whether the alkaloid affects bone mineral density (BMD). Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.

Hepatoprotective effect of majonoside R2, the major saponin from Vietnamese ginseng (Panax vietnamensis).

The hepatoprotective effect of majonoside R 2 (MR2), the major saponin constituent from Vietnamese ginseng ( Panax vietnamensis, Araliaceae), was evaluated in vivo on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced hepatic apoptosis and subsequent liver failure in mice. Pretreatment of mice with MR2 (50 or 10 mg/kg, intraperitoneal) at 12 and 1 h before D-GalN/LPS injection significantly inhibited apoptosis and suppressed following hepatic necrosis. Importantly, the elevation of serum tumor necrosis factor-alpha (TNF-alpha) level, an important mediator for apoptosis in this model, was significantly inhibited by MR2 at a dose of 50 mg/kg. On the other hand, MR2 was found to protect primary cultured mouse hepatocytes from cell death by inhibiting apoptosis induced by D-GalN/TNF-alpha in vitro, as evidenced by DNA fragmentation analysis. These findings suggested that MR2 may have protected the hepatocytes from apoptosis via an inhibition of TNF-alpha production by activated macrophages and a direct inhibition of apoptosis induced by TNF-alpha.