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Methyl protogracillin (NSC-698792): the spectrum of cytotoxicity against 60 human cancer cell lines in the National Cancer Institute's anticancer drug screen panel.

Methyl protogracillin (NSC-698792) was a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor for centuries, in our previous studies. In order to systematically evaluate its potential anticancer activity, methyl protogracillin was tested for its cytotoxicity in vitro against 60 human cancer cell lines in the National Cancer Institute (NCI)'s anticancer drug screen. As a result, it was found that methyl protogracillin was cytotoxic against all the tested cell lines from leukemia and solid tumors in the NCI's human cancer panel; it showed particular selectivity against one colon cancer line (KM12), one central nervous system (CNS) cancer line (U251), two melanoma lines (MALME-3M and M14), two renal cancer lines (786-0 and UO-31) and one breast cancer line (MDA-MB-231) with GI50< or =2.0 microM. The selectivity between these seven most sensitive lines and the least sensitive line (CCRF-CEM) ranged from 26- to 56-fold. In the same cancer subpanel, selectivity more than 15-fold was observed between MDA-MB-231 and MCF-7, NCI-ADR-RES, BT-549 in breast cancer. From a general view of the mean graph, CNS cancer is the most sensitive subpanel, while ovarian cancer and renal cancer are the least sensitive subpanels. Based on an analysis of the COMPARE computer program with methyl protogracillin as a seed compound, no compounds in the NCI's anticancer drug screen database have similar cytotoxicity patterns (mean graph) to that of methyl protogracillin, indicating a potential novel mechanism of the anticancer action involved.

Antineoplastic Agents↗

Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts.

Diosgenin, extracted from the root of wild yam (Dioscorea villosa), has been reported to demonstrate an opportunity for medical application. Vascular endothelial growth factor-A (VEGF-A) plays an important role in bone-related angiogenesis, a critical process occurring during bone formation and fracture healing. In this study, we examine whether diosgenin is able to induce VEGF-A expression and to promote angiogenesis in osteoblasts. For murine MC3T3-E1 preosteoblast-like cells, VEGF-A mRNA and protein expression seemed to be significantly elevated in response to diosgenin in a concentration-dependent fashion. Conditioned media prepared from cells treated with diosgenin induced strong angiogenic activity in either in vitro or ex vivo angiogenesis assay. Furthermore, diosgenin treatment increased the stability and activity of HIF-1alpha protein. Inhibition of HIF-1alpha activity by transfection with DN-HIF-1alpha significantly diminished diosgenin-mediated VEGF-A up-regulation. The use of pharmacological inhibitors or genetic inhibition revealed that both the phosphatidylinositol 3-kinase (PI3K)/Akt and p38 signaling pathways were potentially required for diosgenin-induced HIF-1 activation and subsequent VEGF-A up-regulation. It is noteworthy that an estrogen receptor binding assay revealed that diosgenin has the strong ability to replace [(3)H]estradiol bound to estrogen receptor (IC(50), 10 nM). In addition, the specific estrogen receptor antagonists ICI 182,780 (faslodex) and tamoxifen were noted to be able to strongly inhibit diosgenin-induced, src kinase-dependent Akt and p38 MAPK activation. Taken together, such results provide evidence that diosgenin up-regulates VEGF-A and promotes angiogenesis in preosteoblast-like cells by a hypoxia-inducible factor-1alpha-dependent mechanism involving the activation of src kinase, p38 MAPK, and Akt signaling pathways via estrogen receptor.

3T3 Cells↗

Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the angiogenesis of collagen-induced arthritis in rats.

Qing-Luo-Yin (QLY), a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, is a combination of the extracts of Sophora flavescens Ait., Phellodendron amurense Rupr., Sinomenium acutum Rehd. et Wils. and Dioscorea hypoglauca Palib. The suppressive effect of QLY on the development of angiogenesis was investigated in a rat model of collagen-induced arthritis (CIA). QLY (0.3 g/kg) was orally administered daily for 27 days. Neo-angiogenesis, pannus and cartilage damage, the expression of metalloproteinases (MMP)-3 messenger RNA (mRNA) and the level of the tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the synovium were examined by histology, in situ hybridization and immunohistochemiscal assays, respectively. It was observed that the articular morphological alterations, the over-expression of MMP-3 mRNA and the reduced production of TIMP-1 in CIA rats were significantly ameliorated by QLY. QLY performed about as effectively as tripterygium glycosidorum tablets (0.1 g/kg) extracted from Tripterygium wilfordii Hook. f.. These results indicate that QLY exerts a suppressive effect on the angiogenesis of CIA rats, and suggest that the therapeutic effect of QLY could be due to restoring the balance of MMP-3 and TIMP-1 in rheumatoid synovium.

Animals↗

Effect of SA1, a herbal formulation, on sexual behavior and penile erection.

SA1 is a mixture of 9 Oriental herbs (Korean red ginseng, fermented soybean, Tribulus terrestris, Fructus Rubi, Fructus Lycii, Semen Cuscutae, Dioscorea Rhizome, Fructus Corni and Fructus Crataegi) that are widely used as energizers and vitalizers in the indigenous system of medicine and have been alleged to improve the sexual functions in men. This study evaluated SA1 using both in vitro and in vivo experiments on laboratory animals in order to determine its effect on the sexual behavior and penile erection. The male rats used to examine the copulatory behavior were administered either the vehicle or SA1 (30, 100, 300, 600 mg/kg) orally for 2 weeks. The intracavernous pressure and systemic blood pressure were recorded in anesthetized rats. The responses to acetylcholine and SA1 of rabbit corpus cavernosum strips were also examined. There was an overall increase in the copulatory behavior parameters in the SA1-treated rats, which was reflected by a decrease in the mount and intromission latencies and an increase in the ejaculation latency and mount frequency. SA1 significantly increased the ratio of the intracavernous pressure to mean arterial pressure. In vitro, SA1 significantly enhanced the relaxation responses to acetylcholine. These results suggest that SA1 improves the sexual activity and erectile function.

Animals↗

[Sweet potato in pre-Columbian Polynesia--an overview].

An overview is presented on the reports available so far on sweet potato, Ipomoea batatas, cultivated widely in Polynesia in the pre-Columbian era, with reference to possible ways and presumptive dates of transfer from the Americas to Polynesia, such as (1) Polynesian navigators' travel to Peru, (2) Peruvian fishermen's drift westward, (3) vessel drift, (4) seed drift, (5) root-tuber drift, and (6) transport by birds. The author supports the case (1) as most plausible. Ganshu or Ganchu described in the old Chinese herbal books is identified as Dioscorea esculenta. An introduction of the tuber to China and Japan is briefly mentioned.

Americas↗

Protective effects of Chinese herbs on D-galactose-induced oxidative damage.

A mixture of traditional Chinese herbs ('FTDA') was found to improve several oxidation-related biomarkers in D-galactose-induced mimetic aging mice. FTDA consists of seven herbal components: Cuscutae Semen, Schisandrae Fructus, Dioscoreae Rhizoma, Lonicerae Flos, Nelumbinis Semen, Angelica Radix and Poria, and is routinely used for treating mice with D-galactose-induced oxidative damage. Measurements of antioxidant status, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant status (TAS) and malondialdehyde (MDA) were made on blood, brain and liver tissue collected from animals after 60 days of treatment with D-galactose subcutaneous injections. High-dose, medium-dose and control groups exhibited higher levels of SOD, GSH-Px and TAS in their blood, as well as lower levels of serum MDA activity, compared with the D-galactose group. In the liver, all three experimental and PBS groups demonstrated significant increases in SOD activity and a decrease in MDA activity. The MDA activity decreased in medium-dose, high-dose and PBS groups, while medium-dose and PBS groups demonstrated increased SOD activity compared with that seen in the brain. These results support the efficacy of FTDA in improving the antioxidant status of D-galactose-induced mimetic aging mice.

Animals↗

Increased informativeness of RAPD analysis by detection of microsatellite motifs.

The recently developed random-amplified microsatellite polymorphism (RAMPO) technique detects second-level amplification products that are useful as molecular markers. In the first step of the procedure, genomic DNA is amplified with a single arbitrary or microsatellite-complementary primer. PCR products are then electrophoretically separated, photographed, blotted and hybridized to a 32P-labeled microsatellite probe. Autoradiography reveals highly reproducible, polymorphic, probe-dependent fingerprints, which are different from the ethidium bromide staining patterns. In this paper, we report the successful application of various mono-, tri- and tetranucleotide repeat motifs as RAMPO probes. We also compare the efficiency of arbitrary vs. microsatellite primers for the generation of RAMPO patterns. Repeated rehybridization to different probes has expanded the information contained in a single random-amplified polymorphic DNA (RAPD) gel at least fivefold. Pattern complexity varies with the length and sequence of the probe. Application of the technique to a genetic relatedness study in the genus Dioscorea (yam) yielded highly informative markers, mainly at an interspecific level.

DNA Primers↗

[Clinical and experimental studies of supplemented sini san in treating chronic brucellosis].

OBJECTIVE: To observe the effect of supplemented Sini San (SSNS) in treating chronic Brucellosis (CB). METHODS: One hundred and twenty-seven patients were randomly divided into two groups, 76 cases in the treatment group were treated with SSNS and 51 cases in the control group treated with Dioscorea Nipponica Power. The effect of SSNS on mice model of CB was also observed simultaneously. RESULTS: The short-term effects were that the total effective rate and markedly effective rate of the treatment were 98.7% and 92.1%, which were better than those of the control group (82.4% and 41.2%) respectively, P < 0.01. The long-term follow-up result of the treatment group also showed its superiority to the control group, the total effective rates of the two groups were 98.7% and 51.0%, and the markedly effective rates were 90.8% and 21.6% respectively (P < 0.01). Animal experiments indicated SSNS has obvious effect of antibiotics and immunomodulation. CONCLUSION: SSNS was effective in treating CB, including the long-term follow-up result.

Adult↗

Fingertip dermatitis in a retail florist.

Prevalence of plant contact dermatitis in retail florists varies with exposure, and the number of reports of contact allergy to cut tulips is rather small. Alpha-methylene-gamma-butyrolactone is better known as the cause of both Alstroemeria dermatitis in retail florists and tulip finger in wholesale floral workers who handle the bulbs. Our patient presented with prominent erythema, scaling, and peeling of the skin of the thumb, index, and middle fingers of his right hand. Results of a patch test to alpha-methylene-gamma-butyrolactone were strongly positive, and the patient determined that the exposure had occurred when he stripped leaves from the tulip stems to arrange cut flowers. Other natural sources of the antigen include Alstroemeria; Bomarea; Dioscorea hispida; Erythronium; Gagea; Fritillaria; and at least one species of onion, Allium triquetrum.

4-Butyrolactone↗

Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women.

OBJECTIVES: Many women seek alternatives to hormonal therapies for the management of menopausal symptoms. Among the treatments currently popular are extracts of wild yam (Dioscorea villosa), which are applied topically in the form of a cream. These preparations are known to contain steroidal saponins, including diosgenin, which has been claimed to influence endogenous steroidogenesis. However, there have been no studies of the safety or efficacy of these preparations in the management of menopausal symptoms. METHODS: We therefore conducted a double-blind, placebo-controlled, cross-over study of the effects of a wild yam cream in 23 healthy women suffering from troublesome symptoms of the menopause. After a 4-week baseline period, each woman was given active cream and matching placebo for 3 months in random order. Diaries were completed over the baseline period and for 1 week each month thereafter, and blood and saliva samples were collected at baseline and at 3 and 6 months, for measurement of lipids and hormones. RESULTS: The average age of the subjects was 53.3 +/- 1.1 (SEM) years and average time since last period 4.3 +/- 0.9 years. At baseline, the average body mass index was 27.3 +/- 0.8, cholesterol level 5.7 +/- 0.2 mmol/l and follicle stimulating hormone (FSH) level 74.2 +/- 5.1 IU/l; estradiol levels were undetectable in the majority of cases. After 3 months of treatment, no significant side-effects were reported with either active treatment or placebo, and there were no changes in weight, systolic or diastolic blood pressure, or levels of total serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, FSH, glucose, estradiol, or serum or salivary progesterone. Symptom scores showed a minor effect of both placebo and active treatment on diurnal flushing number and severity and total non-flushing symptom scores, and on nocturnal sweating after placebo, but no statistical difference between placebo and active creams. CONCLUSIONS: This study suggests that short-term treatment with topical wild yam extract in women suffering from menopausal symptoms is free of side-effects, but appears to have little effect on menopausal symptoms. It emphasizes the importance of careful study of treatments for menopausal symptoms if women are to be adequately informed about the choices available to them.

Administration, Cutaneous↗

The effects of sustained delivery of diosgenin on the adrenal gland of female rats.

Diosgenin is a steroidal saponin, which is extracted from the root of Wild Yam (Dioscorea villosa). It has been reported to have tremendous medical applications. In addition, as an herbal extract it appears to be free of any major adverse effects. Recently, Wild Yam has been used to minimize post-menopausal symptoms and is sold unregulated over the counter at a variety of pharmacy and health food stores. The specific objectives of this study were to continuously deliver diosgenin to adult ovariectomized female rats for 45 days and follow changes in body weight, organ weight and histopathological changes in the adrenal gland. Adult female Sprague Dawley rats were divided into three equal groups (n = 54, 250-300 gm BW). Rats in group I served as the control group, animals in group II were ovariectomized and animals in group II were ovariectomized, and supplemented with tricalcium phosphate (TCP) drug delivery system loaded with 500 mg diosgenin. The results indicated that ovariectomized animals had a significant increase in body weight and spleen weights. Slight increases in wet adrenal weights were observed in the ovariectomized group compared to the control animals. Histopathological evaluation of the adrenal gland revealed an increase in the cortical and medullary adrenal areas of the ovariectomized group and a significant decrease in these areas in the diosgenin treated animals (p < 0.001). The information is considered important because reduction in adrenal mass may poses a potential for major endocrine complications.

Adrenal Glands↗

[Apoptosis of human chronic myeloid leukemia k562 cell induced by prosapogenin B of dioscin (P.B) in vitro].

BACKGROUND & OBJECTIVE: The authors have isolated prosapogenin B of dioscin (P.B) newly from Dioscorea futschauensis R. Kunth (Dioscoreaceae) and found that P.B could significantly inhibit the cell proliferation of several human cancer cell lines for the first time. The objective of this paper was designed to investigate whether P.B could inhibit cancer cell proliferation by inducing apoptosis. METHODS: Morphological changes of cell nuclei were observed under invert fluorescence microscope and transmission electron microscope. The changes in the cell size distribution were analyzed by Coulter Multisizer II particle analyzer. DNA ladder and apoptotic cells were analyzed respectively by DNA agarose gel electrophoresis and flow cytometry. RESULTS: The K562 cells treated with 10 micromol/L P.B for 24 hours showed morphological characteristics of apoptotic cells, such as decrease in cellular volume, nuclear chromatin condensation, nuclear fragmentation, and plasma membrane bleb formation. The treatment of K562 cells with 10 micromol/L P.B for 6, 12,and 24 hours caused the increase of the detected DNA ladder and the decrease of normal size cells both in a time-dependent manner. The percentage of apoptotic bodies detected in the sub-G(0)/G(1) peak region by flow cytometry was also increased time-dependently as analyzed as 6.12% for 6 hours, 35.6% for 12 hours and 45.7% for 24 hours treatments, respectively. CONCLUSION: These results suggested that P.B exerts its anti-proliferative effect on K562 cells through inducing apoptosis of the cells.

Antineoplastic Agents, Phytogenic↗

[Investigation on the plant origin and commodity of Chinese drug bixie].

An investigation has been made on the Chinese drug Bixie available in drug market, its folk uses and plant origin in different districts in China. The results reveal that the drug Bixie presently used in different regions in China are derived from 24 species belonging to genus Dioscorea (Family Dioscoreaceae); genus Smilax and Heterosmilax (Family Liliaceae).

China↗

[Effects of extracts of Chinese medicines on Ganoderma lucidum in submerged culture].

Effects of water and ethanol extracts of 10 Chinese medicines, such as Astragalus membranaceus, Coix lachryma-jobi, etc., on biomass and exopolysaccharide of Ganoderma lucidum were studied by submerged culture. The results showed: water extracts of all medicines can improve the culture of G. lucidum except of A. membranaceus, ethanol extracts of C. lachryma-jobi, Dioscorea opposita, Codonopsis pilosula, and Achyranthes bidentata( < 187.5g Medicine/L substrate) can also increase the biomass of G. lucidum, but the ethanol extracts of Angelica sinensis, Dendrobium nobile check the growth of G. lucidum. The production of exopolysa-ccharide can be improved by all the Chinese medicines and their dosage used in this experiment, Although A. sinensis, D. Nobile check the growth of G. lucidum, they could stimulate the secretion of exopolysaccharide in lower dosage. It is concluded that some Chinese medicines, such as C. lachryma-jobi, D. opposita, C. pilosula, etc. can be processed by the fermentation of G. lucidum, and bio-active compound can be produced by adding appropriate Chinese medicine in the substrate to culture G. lucidum.

Biomass↗

Structural characterization of a glucan isolated from Hedyotis diffusa Willd.

OBJECTIVE: To isolate a homogeneous polysaccharide RP from RDP (a crude polysaccharide from Dioscorea opposita Thunb.), and study its preliminary com-position and structure. METHODS: RP was obtained with water extraction, alcohol sedimentation, CTAB deprotein, cellulose column and SephadexG-100 column. The purities of RP were identified by SephadexG-200. PC analysis on its acidic hydrolysates was used to determine the sugar components. Sephadex chromatography was used to mensurate its molecular weight. IR was used to analysis RP. RESULTS: RP was homogeneous. IR indicated that RP had P configurations. The compositon was identified by paper chromatography as glucose, D-mannose, D-galactose. CONCLUSION: The research could provide a theoretical foundation for further development and utilization.

Glucans↗

[Experimental study on anti-senility of the 4 famous Chinese herbs produced in Huaiqing area].

The effects of each of the four famous Chinese herbs and the combination of them on the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and lipid peroxide (LPO) in the blood of young mice were studied. These four famous Chinese herbs produced in Huaiqing area were radix Achyranthis Bidentatae, Flos Chrysanthemi, Rhizoma Dioscoreae and radix Rehmanniae. The results indicated that the combination of the four herbs can evidently increase the activity of SOD and GSH-Px, and can apparently reduce LPO in the blood of young mice. Even each of the four herbs alone can increase the activity of GSH-Px and reduce LPO. It is indicated that these four famous Chinese herbs have the effects on anti-senility.

Aging↗

Anti-sickling effect of dietary thiocyanate in prophylactic control of sickle cell anemia.

As a clinical entity, sickle cell anemia (SCA) is known to be relatively rarer in Africans than in the African-American population of the United States. Paradoxically, sickle cell trait (SCT), the non-anemic, heterozygous condition, is about three times more common among indigenous Africans than in African-Americans. The ratio of SCA to SCT is 1:50 for African-Americans, and less than 1:1,000 for tropical Africans. This etiological disparity is attributed to an anti-sickling agent, thiocyanate, (SCN-) found abundantly in staple African foods, such as the African yam (Dioscorea sp) and cassava (Manihot utilissima). Staple American foods have negligible SCN-concentrations. Nonstaple foods in the American diet, such as carrots, cabbage, and radishes, have SCN- levels far below the African yam and cassava. This finding explains the high incidence of SCA among African-Americans and its rarity in Africans.The author concludes that SCA is a congenital deficiency anemia, ameliorable by prophylactic diets of foods with high SCN- contents. Thus, "thiocyanate deficiency anemia" is nutritionally a more correct clinical status for those born with the homozygous sickle hemoglobin genome. Just as any iron undernourished person can suffer from iron deficiency anemia, sickle hemoglobin homozygotes suffer from "thiocyanate deficiency anemia" when they subsist on SCN-deficient foods. This article reviews the role of dietary SCN- in SCA control.

Anemia, Sickle Cell↗

The disintegration of yam tuber gamma-glutamyl transpeptidase during tuber storage.

As an attempt to understand some aspects of the protein catabolism in the resting yam (Dioscorea rotundata) tuber with respect to the storage problems of the tuber, gamma-glutamyl transpeptidase (gamma-GTP) was isolated from healthy tubers after aerobic storage for varying periods. The molecular weight was determined by SDS-gel electrophoresis and the activity by spectrophotometry using gamma-glutamyl alpha-naphthylamide as substrate. Molecular weight and activity were plotted versus duration of the tuber storage. The molecular weight of the gamma-GTP from newly harvested tuber was 2.2 . 10(5). Both the mol. wt and activity decreased linearly with tuber storage, the two processes having approximately equal first order rate constant, 1.2 . 10(-2)/week, with a half-life of 58 weeks. High molecular weight forms of tuber gamma-GTP when dissociated and gel electrophorized gave in each case a lower molecular weight form that also had enzymic activity. A plot of the mol. wt versus the activity gave a straight line which intersected the mol. wt axis at 200000, which is the mol. wt of the smaller subunit of gamma-GTP. These results show that yam tuber gamma-GTP undergoes progressive disintegration during tuber storage and in this process the components are lost probably from the larger subunit after proteolytic cleavage and subsequent dissociation of the cleaved components.

Drug Stability↗