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PubMed2002

Antiviral activity of seven iridoids, three saikosaponins and one phenylpropanoid glycoside extracted from Bupleurum rigidum and Scrophularia scorodonia.

As part of our screening of antiviral agents from medicinal plants, 11 compounds from plant origin (Bupleurum rigidum and Scrophularia scorodonia), three saikosaponins, seven iridoids and one phenylpropanoid glycoside were tested in vitro against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. Five of these compounds showed antiviral activity against VSV. The percentages of cellular viability at the non-toxic limit concentrations of the active compounds were: verbascoside 53.6 % at 500 microg/ml, 8-acetylharpagide 32.1 % at 500 microg/ml, harpagoside 43.3 % at 450 microg/ml, scorodioside 47.8 % at 500 microg/ml and buddlejasaponin IV 56.9 % at 25 microg/ml. Although none of the saikosaponins were active against HSV-1, the iridoid scorodioside showed moderate in vitro anti-HSV-1 activity (30.6 % at 500 microg/ml). However, none of the compounds tested in this survey had any effect against poliovirus.

Animals↗
PubMed2002

Ginsenosides inhibit EGF-induced proliferation of renal proximal tubule cells via decrease of c-fos and c-jun gene expression in vitro.

Recent epidemiological studies have demonstrated that ginseng intake is associated with a reduced risk for environmentally related cancers. However, the effects of ginsenosides on the proliferation of renal proximal tubule cells have not yet elucidated. This study investigated the effect of total ginsenosides, protopanaxatriol (PT) saponin, and protopanaxadiol (PD) saponin fraction on epidermal growth factor (EGF)-induced renal cell proliferation and, furthermore, c-fos and c-jun gene expression. In the present study, total ginsenosides (10 -6 g/ml) completely blocked EGF-induced DNA synthesis and cell growth. In contrast, the PT and PD fractions partially blocked it. In addition, the EGF-induced increase of c-fos and c-jun gene expression was completely blocked by total ginsenosides and partially by PT and PD saponins. In conclusion, ginsenosides, in part, inhibit EGF-induced cell proliferation via decrease of c-fos and c-jun gene expression in primary cultured rabbit renal proximal tubular cells (PTCs). Abbreviations. EGF:epidermal growth factor PD:protopanaxadiol PT:protopanaxatriol PTCs:primary cultured renal proximal tubule cells

Animals↗
PubMed2003

Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng.

The overexpression of P-glycoprotein (Pgp) or the multidrug resistance-associated protein (MRP) confers multidrug resistance (MDR) to cancer cells. MDR cells can be sensitized to anticancer drugs when treated concomitantly with an MDR modulator. In this study, we investigated whether or not ginseng saponins could reverse MDR mediated by Pgp or MRP. The chemosensitization and drug accumulation effects of ginseng saponins such as the total saponin, protopanaxadiol ginsenosides (PDG), protopanaxatriol ginsenosides (PTG), ginsenosides-Rb 1, -Rb 2, -Rc, -Rg 1 and -Re were tested on the daunorubicin- and doxorubicin-resistant acute myelogenous leukemia sublines (AML-2/D100 and AML-2/DX100), which overexpress Pgp and MRP, respectively. PTG showed cytotoxicity in both sublines and was able to reverse resistance in the AML-2/D100 subline in a concentration-dependent manner. Conversely, other ginseng saponins at concentrations less than 300 microg/mL showed neither cytotoxicity nor chemosensitizing activity in both resistant sublines. Flow cytometry analysis showed that the effect of PTG (100 microg/mL) on drug accumulation of daunorubicin in the AML-2/D100 subline was 2-fold higher than that observed in the presence of verapamil (5 microg/mL) and 1.5 times less than cyclosporin A (3 microg/mL). The maximum non-cytotoxic concentrations of PTG did not appear to increase the Pgp levels, which is in contrast to verapamil and cyclosporin A. PTG at 200 microg/mL or more completely inhibited the azidopine photolabeling of Pgp. The results suggest that PTG has a chemosensitizing effect on Pgp-mediated MDR cells by increasing the intracellular accumulation of drugs through direct interaction with Pgp at the azidopine site. In addition, PTG may have a beneficial effect on cancer chemotherapy with respect to the possibility of long-term use without the concern of Pgp activation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes.

Seven protopanaxatriol-type ginsenosides and their aglycones including PPT, PT, -Re, -Rg (1), -F (1), -Rh (1), 20(R)-Rh (1) which are closely related in structure were studied for their effects on type 1 and type 2 cytokines production from murine splenocytes and their related mechanisms were examined. The results indicate that PPT, PT and ginsenoside-Re show hardly any or weak effects on concanavalin A (Con A)-induced production of IFN-gamma and IL-4. Ginsenoside-Rh (1) and 20(R)-Rh (1) induce a Con A-induced type 1 cytokine pattern by increasing the production of interleukin-12 (IL-12), the expression of IFN-gamma, T-bet and enhancing NF-kappaB DNA binding activity. In contrast ginsenosides-Rg (1) and -F (1) cause a Con A-induced type 2 cytokines response by increasing the expression of IL-4, GATA-3 and enhancing NF-kappaB DNA binding activity. Thus, these protopanaxatriol-type ginsenosides have different immunomodulatory effects, which might explain the complex immunomodulatory effect of Panax ginseng.

Animals↗
PubMed2005

Anti-inflammatory activity of 20(S)-protopanaxadiol: enhanced heme oxygenase 1 expression in RAW 264.7 cells.

20( S)-Protopanaxadiol (PPD) is one of the metabolites of ginsenosides from Panax ginseng. In this study, we demonstrate that PPD inhibits the increase in lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression through inactivation of nuclear factor-kappaB by preventing degradation of inhibitory factor-kappaBalpha. PPD also induces heme oxygenase 1 (HO-1) expression in RAW 264.7 cells, at the mRNA and protein levels, in the presence and absence of LPS. This effect is associated with suppression of LPS-induced nitric oxide (NO) production and iNOS expression. The HO-1 inducer hemin is associated with the suppression of LPS-induced NO production in a dose-dependent manner, and the HO-1 inhibitor tin protoporphyrin attenuates the inhibitory activity of PPD on LPS-induced NO production. These results provide evidence for the role of HO-1 in the inhibition of LPS-induced NO production by PPD.

Anti-Inflammatory Agents↗
PubMed1991

The effects of saikosaponin on macrophage functions and lymphocyte proliferation.

The effects of saikosaponin-d (ssd), isolated from Bupleurum radix, on phagocytic functions of mouse peritoneal macrophages were investigated after treatment in vitro. The macrophages treated with ssd showed a significant increase in PMA-induced chemiluminescence. An increase in phagocytosis was detected after treatment with saikosaponin-b2 (0.1 microM) for 24 h in vitro, while a suppression of phagocytosis was observed following treatment with saikosaponins (0.5 microM). Treatment with ssd markedly increased the random migration of resident peritoneal macrophages, but did not affect the migration towards FMLP. We further investigated the effect of ssd on proliferative responses of spleen cells and found that ssd, which itself has no mitogenic activity, decreased spleen cell proliferative response to T-cell mitogen, but increased the response to B-cell mitogen.

Animals↗
PubMed1992

Inactivation of measles virus and herpes simplex virus by saikosaponin d.

Saikosaponin d, isolated from the roots of Bulpleurum falcatum L. was investigated for both its inactivating effects on some viruses and its antiviral effects against the viruses in vitro. Saikosaponin d at a concentration of more than 5 microM had direct inactivating effects on both measles virus and herpes simplex virus after incubation of the viruses with the agent for more than 10 min at room temperature. In contrast, exposure of poliovirus to even 500 microM of saikosaponin d resulted in no loss of infectivity, while the same concentration of saikosaponin d induced complete loss of infectivity in both measles virus and herpes virus. In addition, saikosaponin d was ineffective against the replication of measles virus, herpes virus, and polio virus at a concentration of 0.1 microM, whereas saikosaponin d did not induce an inhibitory effect on the growth of Vero cells, when Vero cells were treated with saikosaponin d 24 h before the inoculation (pretreatment) and immediately or 24 h after the infection of the viruses (post-treatment).

Animals↗
PubMed2001

Saikosaponin v-1 from roots of Bupleurum chinense DC.

Three triterpenoidal saponins, saikosaponin v-1(1), 6"-O-acetyl-saikosaponin b2 (2) and 6"-O-acetyl-saikosaponin d(3) were isolated from the roots of the title plant and the structures were identified on the basis of spectral analysis. Saikosaponin v-1 is a new compound, which was identified as 3beta,16alpha,23,28-tetrahydroxy-olean-11,13(18)-dien-30-oic acid-3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-fucopyranosyl-30-O-xylitol ester.

Adjuvants, Immunologic↗
PubMed2003

Three new hecogenin glycosides from fermented leaves of Agave americana.

Eight steroidal compounds, including three new hecogenin glycosides, agamenosides D-F, were isolated from the fermented leaves of Agave americana. The structures of the new steroidal saponins were elucidated by spectroscopic data and chemical methods. The activity of the isolated compounds on deformations of mycelia germinated from conidia of Pyricularia oaryzae P-2b was evaluated.

Agave↗
PubMed2004

Antitumor promotional effects of a novel intestinal bacterial metabolite (IH-901) derived from the protopanaxadiol-type ginsenosides in mouse skin.

Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal bacterial metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E(2). The eukaryotic transcription factor NF-kappaB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-kappaB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IkappaBalpha. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-kappaB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.

Animals↗
PubMed2000

High-performance liquid chromatographic analysis of saponin compounds in Bupleurum falcatum.

A mixture of saponin compounds (saikosaponin c, a, and d) in the 70% ethanol extract of a powdered sample of Bupleuri radix are analyzed by an Inertsil ODS-3 C(18) column at a flow rate of 1.0 mL/min and detection wavelength of 203 nm. Well resolved chromatograms of saikosaponin c, a, and d are obtained with a gradient elution of acetonitrile-water from 40:60 (v/v) to 50:50 (v/v). The total time required for a single analysis is approximately 20 min. Calibration curves for saikosaponin c, a, and d are linear up to 2.5 mg/mL. The coefficient of variability values for saikosaponins in the extract are below 4%, and the recoveries for saikosaponin c, a, and d are 95.2 +/- 1.1, 96.5 +/- 0.9, and 96.2 +/- 1.0%, respectively. The changes in saikosaponin contents for a two-year growth of Bupleurum falcatum are measured by the established high-performance liquid chromatography method.

Chromatography, High Pressure Liquid↗
PubMed1979

Effect of food toxicants on voluntary wheel running in rats.

Voluntary wheel running in rats in reaction to a dietary deficiency of iron or food toxicants of natural (dioscin) and environmental (cadmium) origins was used to develop a behavioral model by which rapid detection of food contaminants was accomplished following induction of spontaneous activity by techniques of feed restriction. High levels of voluntary wheel running in reference controls were followed by significant depressions in running activity in animals fed the dietary toxicants. Analyses of blood and liver tissues and depressions of testes size confirmed the presence of the insults to metabolism.

Animals↗
PubMed2005

Radioprotective potential of ginseng.

A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.

Animals↗