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PubMed1996

In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells.

The aim of this study was to determine the ability of the ginsenosides, extracts of Panax ginseng C.A. Meyer, to cause differentiation of F9 teratocarcinoma stem cells as a model system. F9 stem cells cultured in the presence of the ginsenosides together with dibutyryl cyclic AMP (dbcAMP) became parietal endoderm-like cells. Moreover, the expression of differentiation marker genes, such as laminin B1 and type IV collagen, was increased after treatment with the ginsenosides. Among the various purified ginsenosides, Rh1 and Rh2 were the most effective at causing differentiation of F9 cells. Since ginsenosides and glucocorticoid hormone have similar chemical structures, we examined the possibility of the involvement of a glucocorticoid receptor (GR) in the differentiation process induced by the ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarded as a GR was detected in F9 cells cultured in the medium containing the ginsenosides Rh1 or Rh2. In addition, F9 stem cells treated with the ginsenosides Rh1 or Rh2 and with RU486, a glucocorticoid antagonist with a high affinity for the GR, did not differentiate into endoderm cells morphologically, and the expression of laminin B1 gene was not induced in these cells. In a gel mobility shift assay, protein factors capable of binding to the glucocorticoid responsive element (GRE) specifically were detected in nuclear extracts of the ginsenoside-treated F9 cells. Moreover, overexpression of GR by cotransfection of GR expression vector and GRE-luciferase vector enhanced the transactivation activity of GRE promoter in the presence of ginsenosides Rh1 or Rh2 and was further augmented by dbcAMP. In addition, ginsenosides Rh1 and Rh2 bound to a GR assessed by whole-cell binding assay, even though the specific binding affinity was weaker compared to dexamethasone. Based on these data, we suggest that the ginsenosides Rh1 and Rh2 cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a GR or its analogous nuclear receptor.

Animals↗
PubMed1996

Ginsenosides stimulate endogenous production of nitric oxide in rat kidney.

Ginsenosides (GS), saponins purified from Panax ginseng, increase renal blood flow in rats. Nitric oxide (NO) is thought to be the substance endogenously released by GS in preconstricted lungs and cultured endothelial cells. The present study aims to determine whether GS could stimulate endogenous release of NO in rat kidney and whether GS affected the activity of NO synthase in kidney tissues. The serum and urine levels of the stable NO metabolites, nitrite (NO2) and nitrate (NO3) and urinary cGMP levels were measured 8 hr after a single intraperitoneal injection of GS (200 mg/kg) into rats. The effects of the NO synthesis inhibitor, N omega-nitro-L-arginine methyl ester and the NO precursor, L-arginine, on the GS-induced changes were also determined. The activity of NO synthase, as determined by conversion of [14C]-L-arginine to [14C]-L-citrulline, in whole kidney, glomeruli and cortical tubules was also investigated. A single injection of GS resulted in endogenous production of NO as reflected by increase in serum and urine levels of NO2/NO3 and urinary cGMP levels, which were inhibited by the addition of N omega-nitro-L-arginine methyl ester and restored by L-arginine. GS also stimulated the activity of NO synthase in whole kidney as well as glomeruli and cortical tubules, and this increase was significantly prevented by N omega-nitro-L-arginine methyl ester. It was concluded that stimulation in endogenous production of NO by GS may contribute to its antinephritic action and may play a protective role in the kidney.

Animals↗
PubMed2006

Use of complementary therapies in patients with cardiovascular disease.

Previous studies have suggested that patients with chronic medical conditions use complementary and alternative medicine (CAM) at a higher rate than the general population. Despite recent interest in CAM for cardiovascular disease, few data are available regarding patterns of use in patients with cardiovascular disease in the United States. This study used the 2002 National Health Interview Survey and analyzed data on CAM use in 10,572 respondents with cardiovascular disease. Among those with cardiovascular disease, 36% had used CAM (excluding prayer) in the previous 12 months. The most commonly used therapies were herbal products (18%) and mind-body therapies (17%). Among herbs, echinacea, garlic, ginseng, ginkgo biloba, and glucosamine with or without chondroitin were most commonly used. Among mind-body therapies, deep-breathing exercises and meditation were most commonly used. Overall, CAM was used most frequently for musculoskeletal complaints (24% of respondents who used mind-body therapies, 22% who used herbs, 45% who used any CAM). Mind-body therapies were also used for anxiety or depression (23%) and stress or emotional health and wellness (16%). Herbs were commonly used for head and chest colds (22%). Fewer respondents (10%) used CAM specifically for their cardiovascular conditions (5% for hypertension, 2% for coronary disease, 3% for vascular insufficiency, < 1% for heart failure or stroke). Most, however, who used CAM for their cardiovascular condition perceived the therapies to be helpful (80% for herbs, 94% for mind-body therapies). CAM use was more common in younger respondents, women, Asians, and those with more education and greater incomes. In conclusion, CAM use, particularly herbs and mind-body therapies, is common in the United States in patients with cardiovascular disease and mirrors use in the general population. CAM use specifically to treat cardiovascular conditions, however, is less common.

Adult↗
PubMed2005

Spousal correlations for lifestyle factors and selected diseases in Chinese couples.

PURPOSE: Spouses usually are genetically unrelated and share a common living environment. Thus, concordance of diseases in spouses reflects mainly environmental etiologic contributors. The purpose of this study is to investigate spousal associations for selected lifestyle characteristics and common medical conditions. METHODS: Baseline information from 66,130 married couples participating in the Shanghai Women's Health Study was used in this analysis. Husband-wife associations were evaluated by means of logistic regression, using women's lifestyle and medical conditions as dependent variables. Adjustments were made for women's age, education, occupation, and family income in all models. RESULTS: Women were more than twice as likely to be current or former smokers; be regular consumers of alcohol, tea, and ginseng; and exercise regularly if their husbands had the same habit. A statistically significant husband-wife disease association was found for tuberculosis, chronic bronchitis, asthma, chronic gastritis, chronic hepatitis, ulcerative colitis, cholelithiasis, high blood pressure, coronary heart disease, and stroke. CONCLUSIONS: Spouses share common lifestyle habits and health risks. This study supports the hypothesis that the shared marital environment may contribute to similarities in lifestyle and morbidity in spouses and provides a basis for health promotion and prevention strategies that target the spouses of patients.

Aged↗
PubMed2006

[Anaesthetic preoperative assessment of chronic medications and herbal medicine use: a multicenter survey].

OBJECTIVE: This study was undertaken to quantify the use of chronic medication and herbal remedies in the presurgical population. STUDY DESIGN: Prospective multicenter survey. PATIENTS AND METHODS: Adult patients presenting for anaesthesia were directly asked if they were currently using chronic medication or herbal remedies. RESULTS: Among 1057 patients (age 54+/-17 yrs, woman 54%, ASA 2 [1-4], 74%) were taking one or more chronic medication. The most commonly used treatments were, in descending order angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers (15%), beta blockers (11%) and platelet inhibitors (10%). Also, 9% were taking one or more of the following herbal remedies known to interact with the perioperative period: valeriane, ginseng, ginkgo, St John's wort, echinacea and ephedra. Women and patients aged 40-70 yr were most likely to be taking a herbal product (p<0.001 and p<0.01 respectively). CONCLUSION: Chronic medication and herbal remedies are common in patients presenting for anaesthesia. Because of the potential interactions between anaesthetic drugs or techniques and such medication it is important for anaesthetists to be aware of their use.

Adrenergic beta-Antagonists↗
PubMed2004

Compound K induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and increases hyaluronan in hairless mouse skin.

Ginsenosides, the major active ingredients of ginseng, have a variety of biomedical efficacies such as anti-aging, anti-oxidation, and anti-inflammatory activities. To understand the effects of compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol), one of the major metabolites of ginsenosides, on the skin, we assessed the expression levels of about 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. One gene up-regulated by compound K was hyaluronan synthase2 (HAS2). Semi-quantitative RT-PCR showed that compound K increased HAS2 mRNA in time- and dose-dependent manners. ELISA and immunocytochemistry using hyaluronan (HA)-binding protein showed that compound K effectively increased HA production in HaCaT cells. Finally, treatment of compound K on hairless mouse skin increased the amount of HA in the epidermis and papillary dermis. Our study suggests that topical application of compound K might prevent or improve the deteriorations, such as xerosis and wrinkles, partly ascribed to the age-dependent decrease of the HA content in human skin.

Animals↗
PubMed2005

Evidence that the tertiary structure of 20(S)-ginsenoside Rg(3) with tight hydrophobic packing near the chiral center is important for Na(+) channel regulation.

Ginsenosides are the active ingredients of Panax ginseng. Ginsenoside Rg(3) exists as two stereoisomers of carbon-20: 20-S-protopanaxatriol-3-[O-beta-d-glucopyranosyl (1-->2)-beta-glucopyranoside] (20(S)-Rg(3)) and 20-R-protopanaxatriol-3-[O-beta-d-glucopyranosyl (1-->2)-beta-glucopyranoside] (20(R)-Rg(3)). Recently, we reported that 20(S)-Rg(3) regulates voltage-dependent Ca(2+) channel activity and several types of ligand-gated ion channels, whereas 20(R)-Rg(3) does not have this activity. In this study, we investigated the structure-activity relationship of these two stereoisomers by NMR spectroscopy and by measurement of the current in Xenopus oocytes expressing the mouse cardiac voltage-dependent Na(+) channel (Na(v)1.5). We found that 20(S)-Rg(3) but not 20(R)-Rg(3) inhibited Na(+) channel current in a dose- and voltage-dependent manner. The difference between Rg(3) epimers in voltage-dependent ion channel regulation indicates that the structure of 20(S)-Rg(3) may be geometrically better aligned than that of 20(R)-Rg(3) for interaction with receptor regions in Na(+) channels. The (1)H and (13)C NMR chemical shifts, including all hydroxyl protons of 20(S)-Rg(3) and 20(R)-Rg(3), were completely assigned, and their tertiary structures were determined. 20(S)-Rg(3) has more tight hydrophobic packing near the chiral center than 20(R)-Rg(3). Tertiary structures and activities of 20(S)-Rg(3) and 20(R)-Rg(3) indicate that 20(S)-Rg(3) may have stronger interactions with the receptor region in ion channels than 20(R)-Rg(3). This may result in different stereoselectivity of Rg(3) stereoisomers in the regulation of voltage-dependent Na(+) channel activity. This is the first structural approach to ginsenoside action on ion channel.

Animals↗
PubMed2006

Metabolites of ginsenosides as novel BCRP inhibitors.

We have previously shown ginsenosides derived from Panax ginseng exert opposing effects on angiogenesis. Here, we examined protopanaxadiol-containing ginsenosides (Rg3, Rh2, and PPD) and protopanaxatriol-containing ginsenosides (Rg1, Rh1, and PPT) as potential inhibitors of breast cancer resistance protein (BCRP). Among these ginsenosides, metabolites Rh2, PPD, and PPT significantly enhanced the cytotoxicity of mitoxantrone (MX) to human breast carcinoma MCF-7/MX cells which overexpress BCRP. PPD was the most potent followed by Rh2 and PPT. This effect was not seen in sensitive MCF-7 cells. Rg3, Rg1, and Rh1 were ineffective in either MCF-7 or MCF-7/MX cells. PPD, Rh2, and PPT were able to inhibit MX efflux in MCF-7/MX cells. PPD and Rh2 also increased MX uptake. In inside out membrane vesicles from Lactococcus lactis cells expressing BCRP, only PPD was found to significantly inhibit BCRP-associated vanadate sensitive ATPase activity. These results indicate that metabolites PPD, Rh2, and PPT were inhibitors of BCRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.

Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells.

Amino Acid Sequence↗
PubMed2006

The angiosuppressive effects of 20(R)- ginsenoside Rg3.

Aberrant angiogenesis is an essential step for the progression of solid tumors. Thus anti-angiogenic therapy is one of the most promising approaches to control tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg3 (Rg3), one of the active compounds present in ginseng root, to interfere with the various steps of angiogenesis. Rg3 was found to inhibit the proliferation of human umbilical vein endothelial cells (HUVEC) with an IC50 of 10 nM in Trypan blue exclusion assay. Rg3 (1-10(3) nM) also dose dependently suppressed the capillary tube formation of HUVEC on the Matrigel in the presence or absence of 20 ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring assay were both significantly attenuated by Rg3. In addition, Rg3 (150 and 600 nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation of basement membrane in angiogenesis and tumor metastasis present in the culture supernatant of Rg3-treated aortic ring culture were found to decrease in their gelatinolytic activities. Taken together, these data underpin the anti-tumor property of Rg3 through its angiosuppressive activity.

Angiogenesis Inhibitors↗
PubMed2005

Anti-apoptotic activity of Bak Foong Pills and its ingredients on 6-hydroxydopamine-induced neurotoxicity in PC12 cells.

Bak Foong Pills (BFP), a traditional Chinese medicine used for centuries for the enhancement of women's health, was shown to display neuro-protective activity in the 1-methyl-4-phenyl-1,2,4,6,-tetrahydro-pyridine (MPTP)-induced mouse model in a previous study. In order to elucidate its mechanism of action, we investigated the anti-apoptotic properties of Bak Foong Pills and its main ingredients, including Panax ginseng, Angelica sinensis, Glycyrrhiza uralensis, and Ligusticum chuanxiong, in the 6-hydroxydopamine (6-OHDA)-treated PC12 cell model. The addition of the neurotoxin could cause significant cell death and reduction of cell proliferation, as shown in the results determined by MTT assay, nitric oxide (NO) measurement and flow cytometric propidium iodine (PI) staining analysis, while pre-treatment of PC12 cell with either BFP or its main ingredients prevented the toxicity to some degree. In addition, the neurotoxin caused an elevated activation of caspase-3, the key enzyme for activation of the cellular apoptotic cascade, whereas BFP or its main ingredients inhibited the activation of caspase-3. These results strongly indicate that BFP and its main ingredients may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases, such as Parkinson's disease.

Animals↗
PubMed2004

Cadmium, mercury and lead in medicinal herbs in Brazil.

Samples of herbal medicine used in Brazil were analyzed, after nitric digestion, for the content of cadmium, mercury and lead, by atomic absorption spectrophotometry. Fifteen samples of ginkgo biloba (Ginkgo biloba), 13 of celastraceae (Maytenus ilicifolia), 14 of cascara buckthorn (Rhamnus purshiana), 13 of eggplant (Solanum melongena), 15 of horse chestnut (Aesculus hippocastanum), 13 of Brazilian ginseng (Pffafia glomerata), 17 of centella asiatic (Hydrocotyle asiatica), 13 of guarana (Paullinia cupana), 12 of artichoke (Cynara scolymus) and five samples of chlorella (Chlorella pyrenoidosa) were analyzed. Cadmium, mercury and lead were not detected (limit of quantifications of 0.20, 0.01 and 2.0 mg/kg, respectively) in any sample of artichoke, eggplant and guarana. Cadmium was found in samples of the other medicinal herbs at levels up to 0.74 microg/g and mercury up to 0.087 microg/g. Three samples of horse chestnut contained 153, 156 and 1480 microg Pb/g, while the highest concentration found in the other samples analyzed was 22 microg Pb/g. The estimated lead intake through the consumption of horse chestnut reached 440% of Provisional Tolerable Weekly Intake (PTWI), and might be of concern to consumers if the medicine was taken on a long-term basis. Cadmium and mercury exposure through the herbal medicines does not appear to be of health concern.

Brazil↗
PubMed2006

Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells.

We here provide definitive evidence that ginsenoside-Rg1, the pharmacologically active component of ginseng, is a functional ligand of the glucocorticoid receptor (GR) as determined by fluorescence polarization assay. Rg1 increased the phosphorylation of GR, phosphatidylinositol-3 kinase (PI3K), Akt/PKB and endothelial nitric oxide synthase (eNOS) leading to increase nitric oxide (NO) production in human umbilical vein endothelial cell. Rg1-induced eNOS phosphorylation and NO production were significantly reduced by RU486, LY294,002, or SH-6. Also, knockdown of GR completely eliminated the Rg1-induced NO production. This study revealed that Rg1 can indeed serve as an agonist ligand for GR and the activated GR can induce rapid NO production from eNOS via the non-transcriptional PI3K/Akt pathway.

Chromones↗
PubMed2006

Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4+ T cell.

Ginsenosides, the most important component isolated from Panax ginseng, exhibits a variety of biological activities. Particularly, ginsenoside Rg1 is known to have various immune-modulating activities such as increase of immune activity of T helper (Th) cells. In this present work, we investigated the effect of the Rg1 on Candida albicans growth. Results showed that direct interaction of the Rg1 to C. albicans yeast cells resulted in no growth inhibition as tested by agar diffusion susceptibility method. Reversely, mice given the Rg1 intraperitoneally (i.p.) before intravenous (i.v.) challenge with live C. albicans yeast cells protected the mice to experimental disseminated candidiasis. By kidney candidal CFU (colony forming unit) determination, the disease severity of the Rg1-treated mice was confirmed far less than Rg1-untreated control mice. The protection was transferable by CD4+ T cells (RGCD4T) isolated from Rg1-treated mice. ELISA analysis revealed that there were cytokine inductions of IFNgamma, IL-2, IL-4 and IL-10 from the RGCD4T, demonstrating the Th1-lineage development of predominant IFNgamma and IL-2 production. Anti-mouse IFNgamma antibody treatment of Rg1-treated mice abolished the protection to disseminated disease. Our studies show that ginsenoside Rg1 helps the host resists disseminated candidiasis by the CD4(+) T cell-mediated immune response led from a Th1-dominant cytokine response.

Animals↗
PubMed2005

Green tea and the skin.

Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action.

Animals↗
PubMed2006

Availability of weight-loss supplements: Results of an audit of retail outlets in a southeastern city.

The sale of nonprescription weight-loss products accounts for millions of dollars spent by Americans trying to lose weight, yet there is little evidence for effectiveness and there are multiple safety concerns. The purpose of this study was to determine what products, and ingredients within products, were available at retail outlets in a metropolitan area. A purposive sampling strategy identified 73 retail outlets. An audit form was used to collect information from product labels. The audit identified 402 products containing 4,053 separate ingredients. The mean number of ingredients per product was 9.9+/-8.96 (range = 1 to 96). A database search was conducted regarding evidence for effectiveness, safety precautions, and side effects for the 10 ingredients that appeared most often across products. Modest evidence of effectiveness exists for green tea (Camellia sinensis), chromium picolinate, and ma huang (Ephedra major). For the remaining seven (ginger root [Zingiber officinale], guarana [Paullinia cupana], hydroxycitric acid [Garcinia cambogia], white willow [Salix alba], Siberian ginseng [Eleutherococcus senticosus], cayenne [Capsicum annuum], and bitter orange/zhi shi [Citrus aurantium]), inadequate or negative evidence exists. Although precautions and contraindications were found for all 10 ingredients, the strongest concerns in the literature appear for ma huang, bitter orange, and guarana. Our audit revealed numerous weight-loss products available to consumers, yet there is little evidence to support the effectiveness of the top 10 ingredients identified and many potential adverse reactions; therefore, food and nutrition professionals should discuss dietary supplement use with their clients.

Anti-Obesity Agents↗
PubMed2006

Use of complementary medicine and dietary supplements among U.S. adolescents.

PURPOSE: Use of complementary and alternative medicine (CAM) is increasing, but some dietary supplements have potentially negative side effects. This study examines CAM and dietary supplement use among a national sample of adolescents. METHODS: A total of 1280 adolescents 14-19 years old completed an online survey in 2002 about lifetime and past-30-day use of all CAM modalities, and specifically about use of herbal medicines and dietary supplements. We e-mailed invitations to 12,353 members of Harris Interactive's national Youth Query panel, and filled age/gender quotas sample targets. Data were then weighted to reflect the U.S. adolescent population by gender, race/ethnicity, urbanicity, region, parents' education, propensity to be online, and likelihood of nonresponse. Chi-square and logistic regression analyses were done using SPSS. RESULTS: Seventy-nine percent of adolescents had used CAM in their lifetime, 48.5% in the previous month; 46.2% had used dietary supplements in their lifetime, 29.1% in the previous month; 9.3% reported concurrent use of supplements and prescription medication in the previous month. Factors associated with CAM and supplement use included being female, positive attitudes towards CAM, and being age 16-17 years (rather than in younger or older age groups). Commonly used supplements included ginseng, zinc, echinacea, ginkgo, weight loss supplements, and creatine. CONCLUSIONS: Many adolescents use CAM and dietary supplements, including a significant number concurrent with prescription medications. Commonly used supplements (weight loss supplements and creatine) are closely linked to attempts to change body shape. Health care providers should be aware of CAM and supplement use by adolescents.

Adolescent↗