Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden.

The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.

Nitric oxide is involved in the immunomodulating activities of acidic polysaccharide from Panax ginseng.

The effects of an acidic polysaccharide isolated from the ethanol-insoluble and water-soluble fraction of Panax ginseng C. A. Meyer on immunomodulating activities were investigated. A high output nitric oxide synthase (iNOS) was shown in female BALB/c mice administered intraperitoneally with the acidic polysaccharide from ginseng. Newly synthesized iNOS protein was also observed in peritoneal macrophages cultured with interferon-gamma and the acidic polysaccharide. Spleen cells from acidic polysaccharide-treated mice did not proliferate in response to concanavalin A, but restored the responsiveness by the cotreatment of NG-monomethyl-L-arginine (NMMA) with concanavalin A. The treatment of mice with aminoguanidine, a specific iNOS inhibitor, alleviated the acidic polysaccharide-induced suppression of antibody response to sheep red blood cells. Present results suggest that the immunomodulating activities of the acidic polysaccharide were mediated by the production of nitric oxide.

Differential expression of protein kinase C subtypes during ginsenoside Rh2-lnduced apoptosis in SK-N-BE(2) and C6Bu-1 cells.

We examined the modulation of protein kinase C (PKC) subtypes during apoptosis induced by ginsenoside Rh2 (G-Rh2) in human neuroblastoma SK-N-BE(2) and rat glioma C6Bu-1 cells. Apoptosis induced by G-Rh2 in both cell lines was confirmed, as indicated by DNA fragmentation and in situ strand breaks, and characteristic morphological changes. During apoptosis induced by G-Rh2 in SK-N-BE(2) cells, PKC subtypes alpha, beta and gamma were progressively increased with prolonged treatment, whereas PKC delta increased transiently at 3 and 6 h and PKC epsilon was gradually down-regulated after 6 h following the treatment. On the other hand, PKC subtype zeta markedly increased at 24 h when maximal apoptosis was achieved. In C6Bu-1 cells, no significant changes in PKC subtypes alpha, gamma, delta, epsilon and zeta were observed during apoptosis induced by G-Rh2. These results suggest the evidence for a possible role of PKC subtype in apoptosis induced by G-Rh2 in SK-N-BE(2) cells but not in C6Bu-1 cells, and raise the possibility that G-Rh2 may induce apoptosis via different pathways interacting with or without PKC in different cell types.

Antifeeding activity of isoquinoline alkaloids identified in Coptis japonica roots against Hyphantria cunea (Lepidoptera: Arctiidae) and Agelastica coerulea (Coleoptera: Galerucinae).

The anti-feeding activity of 3 isoquinoline alkaloids identified from roots of Coptis japonica Makino toward 4th-instar larvae of Hyphantria cunea Drury and adults of Agelastica coerulea Baly was examined using the leaf-dipping bioassay. The biologically active constituents of the Coptis roots were characterized as the isoquinoline alkaloids berberine, palmatine and coptisine by spectroscopic analysis. In a test with H. cunea larvae, the anti-feeding activity was much more pronounced in an application of a mixture of palmatine iodide and berberine chloride (1:1, wt:wt) at 250 ppm (82.3%) and 500 ppm (100%), compared with palmatine iodide (76.0%) and berberine chloride (75.4%) alone at 500 ppm. These results indicate a synergistic effect. With A. courulea adults, berberine chloride showed 57.5 and 91.1% anti-feeding activity at 125 and 250 ppm, respectively; whereas, weak activity was obtained in application of 500 ppm of palmatine iodide (41.4%) and coptisine chloride (52.4%) alone. The Coptis root-derived compounds merit further study as potential insect-control agents.

Ginsenoside Rh2 induces apoptosis independently of Bcl-2, Bcl-xL, or Bax in C6Bu-1 cells.

In ginsenoside Rh2-treated rat glioma C6Bu-1 cells, apoptotic morphological changes, such as cell shrinkage, chromatin condensation and pyknosis were confirmed by means of electron microscopy. To evaluate whether induction of apoptosis by ginsenoside Rh2 is mediated by the members of Bcl-2 family, we first established C6Bu-1 cells overexpressing Bcl-2. It was demonstrated that the expression of Bcl-2, Bcl-xL and Bax was not altered in ginsenoside Rh2-treated C6Bu-1 cells. Bcl-2 overexpressing C6Bu-1 cells failed to prevent from ginsenoside Rh2-induced cell death. These results suggest the existence of other apoptotic pathway that requires induction of apoptosis by ginsenoside Rh2 rather than the pathway through Bcl-2, Bcl-xL or Bax in C6Bu-1 cells.

Acyl-CoA: cholesterol acyltransferase inhibitory activity of ginseng sapogenins, produced from the ginseng saponins.

Ginseng sapogenins were produced from ginseng saponins, isolated from Korean ginseng roots. Ginseng saponins very mildly inhibited acyl-CoA:cholesterol acyltransferase (ACAT) in vitro, however, the sapogenins showed strong inhibitory activity on microsomal ACAT. Therefore, the sapogenins will be one of key ingredients of ginseng affected a lowering of the serum total cholesterol level.

Platelet activating factor antagonist activity of ginsenosides.

Ginseng saponins and their degradation products have been screened for antagonist activity towards [3H]PAF (platelet activating factor) in washed rabbit platelet receptor binding studies. 20(S)- and delta20-ginsenosides Rg3, protopanaxadiol-type saponins, were found to be relatively potent PAF antagonists (IC50 = 4.9 x 10(-5) M and 9.2 x 10(-5) M, respectively).

Anticomplementary activity of ginseng saponins and their degradation products.

The anticomplementary activity of ginseng saponins and their degradation products obtained by chemical treatment of Korean red ginseng saponins was investigated. The total saponin and its major components showed strong anticomplementary activity and their structure-activity relationship was evaluated.

Ginsenoside Rf2, a new dammarane glycoside from Korean red ginseng (Panax ginseng).

A new dammarane glycoside named ginsenoside Rf2 has been isolated from Korean red ginseng (Panax ginseng) and its chemical structure has been elucidated as 6-O-[alpha-L-rhamnopyranosyl (1-->2) beta-D-glucopyranosyl]dammarane-3 beta, 6 alpha, 12 beta, 20(R), 25-pentol by chemical and spectral methods.

Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition.

A possible role of cytochrome P450 (P450) inhibition by red ginseng saponins in carbon tetrachloride (CCl4)-induced lipid peroxidation was investigated in liver microsomes prepared from male Sprague Dawley rats. The total saponin of red ginseng standardized on ginsenosides-Rb1, -Rb2, -Rc, -Rd, -Re, and -Rg1 whose composition was studied in our previous report was used in the present study. The standardized saponin of red ginseng showed inhibitory effects on P450-associated monooxygenase activities in a dose-dependent manner, particularly p-nitrophenol hydroxylase activity which has been known to represent CCl4-activating P450 2E1 enzyme. Meanwhile, silymarin enhanced the activity of P450 2E1 enzyme in liver microsomes. When the lipid peroxidation was induced by incubating rat liver microsomes with CCl4 in the presence of NADPH, the standardized saponin significantly blocked the formation of thiobarbituric acid-reactive substances at the same concentrations showing P450 inhibition in liver microsomes. Silymarin revealed more potent protection against CCl4-induced lipid peroxidation. When the lipid peroxidation was induced by FeCl3, in which metabolic activation may not be required, only silymarin could protect the lipid peroxidation in liver microsomes. Taken together, our present results indicated that the inhibitory effects of red ginseng saponin on P450 enzymes may have a critical role in CCl4-induced lipid peroxidation in rat liver microsomes and that the mechanism of hepatoprotection by red ginseng saponin may be distinct from that of silymarin.

Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats.

The protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity were investigated in male Sprague Dawley rats. The total saponins of red ginseng standardized on ginsenosides-Rb1, -Rb2, -Rc, -Rd, -Re, and -Rg1 were used in the present study. The rats were administered the standardized saponins of red ginseng orally at 50, 100, and 200 mg/kg for 7 consecutive days, followed by an administration of carbon tetrachloride at 0.4 ml/kg in corn oil intraperitoneally for 24 h. The administration of saponin changed neither body and organ weights nor hematological and serum clinical parameters. The elevation of SGPT and SGOT activities induced by carbon tetrachloride was partially recovered by the administration of the saponin. The liver vacuolization and lymphoid cell aggregation by carbon tetrachloride were clearly recovered by the red ginseng saponins as examined histologically. The present results indicated that the standardized saponins of red ginseng used in these studies may partially recover the hepatotoxicity induced by carbon tetrachloride in male Sprague Dawley rats.

Ginsenoside Rh4, a genuine dammarane glycoside from Korean red ginseng.

A genuine glycoside, named ginsenoside Rh4, was isolated from Korean red ginseng (Panax ginseng C. A. Meyer) through repeated column chromatography, and its chemical structure was established to be 6-O-beta-D-glucopyranosyldammar-20(22),24-diene-3 beta,6 alpha,12 beta-triol by spectral and chemical methods. The stereochemistry of a double bond at C-20(22) of ginsenoside Rh4 was characterized as (E) from a NOESY experiment in the 1H-NMR of the aglycone. Cytotoxic activities of ginsenoside Rh4 and its aglycone against cancer cell lines were evaluated by use of the SRB method.

In vitro and in vivo antitumoral phenanthrenes from the aerial parts of Dendrobium nobile.

Two phenanthrenes were isolated from the aerial part of Dendrobium nobile Lindl. and their structures were identified to be 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (1) and denbinobin (2), among which the former has been first isolated from this plant. These two compounds were found to be cytotoxic against A549 (human lung carcinoma), SK-OV-3 (human ovary adenocarcinoma), and HL-60 (human promyelocytic leukemia) cell lines. Compound 1 also showed antitumor activity on the life span of ICR mice intraperitoneally implanted with 1 x 10(6) cells of sarcoma 180.

Euonymoside A: a new cytotoxic cardenolide glycoside from the bark of Euonymus sieboldianus.

A new cytotoxic cardenolide glycoside, euonymoside A (1), was isolated from the bark of Euonymus sieboldianus. The structure of 1 was elucidated as acovenosigenin A-3-O-beta-D-glucopyranosyl (1-->2)-alpha-L-rhamnopyranoside. The IC50 values of 1 against A549 (human lung carcinoma) and SK-OV-3 (human ovary adenocarcinoma) were 0.06 and 0.4 micrograms/ml, respectively.

Indonesian medicinal plants. I. Chemical structures of calotroposides A and B, two new oxypregnane-oligoglycosides from the root of Calotropis gigantea (Asclepiadaceae).

Two new oxypregnane-oligoglycosides named calotroposides A (1) and B (2) have been isolated from the root of Calotropis gigantea (Asclepiadaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated by chemical and spectroscopic methods as 12-O-benzoyllineolon 3-O-beta-D-cymaropyranosyl(1----4)-beta-D-oleandropyranosyl( 1----4)- beta-D-oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)-beta-D- cymaropyranoside and 12-O-benzoyldeacetylmetaplexigenin 3-O-beta-D-cymaropyranosyl(1---4)-beta-D-oleandropyranosyl(- ---4)- beta-D-oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)- beta-D-cymaropyranoside, respectively.