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.

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.

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.

Antiproliferative activity of Vietnamese medicinal plants.

Methanol, methanol-water (1:1) and water extracts were prepared from seventy-seven Vietnamese medicinal plants and tested for their antiproliferative activities against human HT-1080 fibrosarcoma cells. Among them, fifteen extracts including seven methanol extracts of Caesalpinia sappan, Catharanthus roseus, Coscinium fenestratum, Eurycoma longifolia, Hydnophytum formicarum and Streptocaulon juventas (collected at two areas), six methanol-water (1:1) extracts of Cae. sappan, Cat. roseus, Co. fenestratum, H. formicarum and S. juventas (at two areas), and two water extracts of Cae. sappan and S. juventas exhibited antiproliferative activities in a concentration-dependent manner. Their antiproliferative activities against human cervix HeLa adenocarcinoma, human lung A549 adenocarcinoma, murine colon 26-L5 carcinoma, murine Lewis lung carcinoma (LLC) and murine B16-BL6 melanoma cells were then examined. Co. fenestratum showed selective activity against lung carcinoma and/or lung metastatic cell lines, A549, LLC and B16-BL6, while H. formicarum and S. juventas showed selective activity against human tumor cell lines, HeLa and A549. Characteristic morphological change and DNA fragmentation indicated the antiproliferative activity to be due to the induction of apoptosis.