A natural food sweetener with anti-pancreatic cancer properties.

Mogroside V is a triterpenoid isolated from the traditional Chinese medical plant Siraitia grosvenorii. Mogroside V has a high degree of sweetness and a low calorific content. Herein, we found that mogroside V possesses tumor growth inhibitory activity in in vitro and in vivo models of pancreatic cancer by promoting apoptosis and cell cycle arrest of pancreatic cancer cells (PANC-1 cells), which may in part be mediated through regulating the STAT3 signaling pathway. These results were confirmed in vivo in a mouse xenograft model of pancreatic cancer. In xenograft tumors, Ki-67 and PCNA, the most commonly used markers of tumor cell proliferation, were downregulated after intravenous administration of mogroside V. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that mogroside V treatment promoted apoptosis of pancreatic cancer cells in the xenograft tumors. Furthermore, we found that mogroside V treatment significantly reduced the expression of CD31-labeled blood vessels and of the pro-angiogenic factor vascular endothelial growth factor in the xenografts, indicating that mogroside V might limit the growth of pancreatic tumors by inhibiting angiogenesis and reducing vascular density. These results therefore demonstrate that the natural, sweet-tasting compound mogroside V can inhibit proliferation and survival of pancreatic cancer cells via targeting multiple biological targets.

Triterpenoid saponins from Platycodon grandiflurum.

A new bisdesmosidic saponin, named deapio-platycoside E (1), together with two known triterpenoid saponins (2, 3) were isolated from the roots of Platycodon grandiflorum (Jacq.) A. D.C. Their structures were elucidated by spectroscopic and chemical methods.

Studies on the chemical constituents of Valeriana fauriei Briq.

Nine compounds were isolated from the roots of Valeriana fauriei Briq, of which one is a new germacrane-type sesquiterpenoid named as valerianin E and its structure was elucidated as bicyclo[8, 1, 0] 5beta-hydroxyl-7beta-acetoxyl-5alpha,11, 11'-trimethyl-E-1(10)-ene-4alpha, 15-olide (1). In addition, two were first reported from this genus and the others were isolated for the first time from the title plant.

Effects of ginsenosides from Panax ginseng on cell-to-cell communication function mediated by gap junctions.

Gap junctions have been shown or are believed to be involved in the pathogenesis of many inherited and acquired human diseases. Agents that regulate the gap junction-mediated intercellular communication (GJIC) function may facilitate prevention and treatment of GJIC-involved diseases. In the present study we examined the effects of 27 ginsenosides isolated from Panax ginseng on GJIC. The results show that compounds 1 (oleanolic acid), 2 (ginsenoside-R0), 3 (ginsenoside-Rb1), 5 (ginsenoside-Rb2), 7 (ginsenoside-Rd), 8 (ginsenoside-Rg3), 12 (panaxadial), 13 (notoginsenoside-R4), 17 [ginsenoside-Rg2 (20S)], 18 (ginsenoside-Rf), and 26 (ginsenoside-F3) did not obviously affect GJIC, whereas compounds 4 (ginsenoside-Rc), 6 (ginsenoside-Rb3), 9 (ginsenoside-Rd2), 10 (notoginsenoside-Fe), 11 (ginsenoside-Rh2),14 (ginsenoside-Ra1), 15 (ginsenoside-Re), 16 [ginsenoside-Rg2 (20R)], 19 (ginsenoside-Ia), 20 [ginsenoside-Rh1 (20S)], 21 [ginsenoside-Rh1 (20R)], 22 (ginsenoside-F1), 23 (protopanaxatriol), 24 (panaxatriol), 25 (ginsenoside-Rg1), and 27 (chikusetsaponin-L8) induced GJIC reductions at various degrees. Compounds 2, 7, and 8 protected against the tyrosine phosphatase inhibitor vanadate-induced GJIC reduction, while compounds 1, 5, 7, and 17 inhibited the cytokine interleukin 1 alpha (IL-1alpha)-induced reduction in GJIC. Nevertheless, no compounds protected against the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced GJIC inhibition. On the other hand, GJIC reductions induced by compounds 6, 9,10, 20, 21, 22, 24, and 25 were inhibited by the tyrosine kinase (TK) inhibitor genistein, while GJIC reductions induced by compounds 6, 9, 14, 16, 19, 21, and 24 were attenuated in the presence of the PKC inhibitor calphostin C. However, GJIC reductions induced by compounds 4, 23, and 27 were not inhibited either by genistein or by calphostin C. These data indicate that various mechanisms are responsible for effects of ginsenosides on GJIC.

Six new dammarane-type triterpene saponins from the leaves of Panax ginseng.

Six new minor saponins, together with known ginsenosides, were isolated from the leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, -Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of chemical and physicochemical evidence to be as follows: ginsenoside-Rh5: 3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D-glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)-tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8: 3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta-D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl 3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside (6).

The inhibitory effects of ginsenosides on protein tyrosine kinase activated by hypoxia/reoxygenation in cultured human umbilical vein endothelial cells.

27 individual ginsenosides and aglycones, together with five extracts from ginseng roots, ginseng leaves, American ginseng roots, American ginseng leaves and non-saponin fraction from roots of Panax ginseng, were tested for their effects on protein tyrosine kinase (PTK) activation induced by an in vitro hypoxia/reoxygenation (H/R) model in cultured human umbilical vein endothelial cells (HUVEC). The results indicated that ginsenoside-Rb1 (3), -Rd (7), -Ra1 (1) and -Ro (27) showed significant inhibitory effects on PTK activation induced by H/R. Dose-response experiments revealed that ginsenoside-Rb1 was the most active compound and it completely blocked PTK activation at a wide range of concentrations. Most protopanaxadiol-type ginsenosides and some protopanaxatriol-type saponins also showed significant effects on PTK activation. However, the crude extracts did not protect against H/R-induced PTK activation.

Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals.

The effect of ginseng saponins isolated from red ginseng (a steamed and dried root of Panax ginseng) has been studied in a cyclophosphamide (CPM)-induced hyperlipidemia model in fasted rabbits. In this model, chylomicrons and very low density lipoprotein (VLDL) accumulation was known to occur as a result of reduction in lipoprotein lipase (LPL) activity in the heart and heparin-releasable heart LPL. Oral administration of ginseng saponins at a dose of 0.01 g/kg for 4 weeks was found to reverse the increase in serum triglycerides (TG) and concomitant increase in cholesterol produced by CPM treatment, especially in chylomicrons and VLDL. In addition, ginseng saponins treatment led to a recovery in postheparin plasma LPL activity and heparin-releasable heart LPL activity, which were markedly reduced by CPM treatment. In rats given 15% glycerol/15% fructose solution, postheparin plasma LPL activity declined to two third of normal rats, whereas ginseng saponins reversed it to normal levels. In the present study we first demonstrated that ginseng saponins sustained LPL activity at a normal level or protected LPL activity from being decreased by several factors, resulting in the decrease of serum TG and cholesterol.