Dioscorea villosa (wild yam) induces chronic kidney injury via pro-fibrotic pathways

School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Food and Chemical Toxicology (Impact Factor: 2.9). 10/2008; 46(9):3122-31. DOI: 10.1016/j.fct.2008.06.090
Source: PubMed


Dioscorea villosa (wild yam) rhizome extract is a medicinal herb that is commonly used to treat symptoms of menopause and rheumatoid arthritis. We had evidence from previous in vitro experiments that this extract is toxic and pro-fibrotic in renal cells and aimed to test whether this occurs in vivo. Sprague-Dawley rats received 0.79g/kg/d D. villosa extract in their food or no treatment over 7, 14 and 28d (n=4 per group). Kidney and liver tissues were collected for protein extraction and Western immunoblots or fixed for special histologic stains, immunohistochemistry (IHC) and microscopy. Collagen deposition was assessed using Masson's trichrome staining and morphometry. Macrophage infiltration (ED-1), epithelial-to-mesenchymal transdifferentiation or activation of fibroblasts (vimentin, alpha-SMA), and pro-fibrotic growth factors (TGFss1, CTGF) were assessed using IHC. Protein expression levels of the pro-inflammatory cytokine, TNF-alpha, the pro-fibrotic transcription factor, NFkappaB, a measure of oxidative stress (heme oxygenase-1), alpha-SMA, vimentin and TGFss1 were determined. Results showed that kidneys of the treated animals had significantly increased collagen, vimentin, TGFbeta1, NFkappaB, EDI, CTGF and alpha-SMA by 28d. In the liver, there was increased ED-1 and TGFbeta1 in the centrilobular zone at 28d in treated animals. In conclusion, there was no acute reno- or hepato-toxicity associated with administration of D. villosa. However, there was an increase in fibrosis in the kidneys and in inflammation in livers of rats consuming D. villosa for 28 days. Long term supplementation with D. villosa may be best avoided, especially in people with compromised renal function and in those who need to take other drugs which may alter kidney function.

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    • "Tubers from the Dioscorea genus were widely used in CM to relieve the menopausal syndrome [89]. A tuber storage protein from Dioscorea batatas, dioscorin, was isolated and purified by ammonium sulfate fractionation, DE-52 ion-exchange chromatography, and Sephadex G-75 column chromatography [90]. "
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    ABSTRACT: Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.
    Chinese Medicine 07/2014; 9(1):19. DOI:10.1186/1749-8546-9-19 · 1.49 Impact Factor
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    • "The chemical composition of DV includes protodioscin, methylprotodioscin, dioscine, prosapogenin, epiafzelechin glucopyranoside, saponin glycosides, steroidal saponin, diosgenin, alkaloids, tannins and phytoestrogen [8-12]. In addition, the rhizomes and roots of DV have been popularly used as a non-conventional treatment of the symptoms of menopause [13,14], rheumatoid arthritis and hypoprogesteronaemia [8,11]. "
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    ABSTRACT: Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean +/- S.D., and statistical analysis of the data were performed with the Student's t-test or one-way analysis of variance (ANOVA) followed by Tukey's test. In all cases differences were considered significant if p < 0.05. HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg[fraction slash]kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant inhibition of inflammatory pain (p < 0.0001). Significant inhibition of leukocyte migration was observed with doses of 100 (p < 0.001), 200 (p < 0.01) and 400 mg/kg (p < 0.01). Haematological, biochemical and histopathological data obtained in both acute and subchronic toxicological assays revealed only unremarkable changes, which are unlikely to indicate DV toxicity with oral administration. We found that DV possesses antinociceptive and anti-inflammatory properties in rodent models. In addition, no acute or subchronic toxicity was evident when the herbal extract was administered orally. These results supporting the folkloric usage of the plant to treat various inflammatory diseases.
    BMC Complementary and Alternative Medicine 07/2013; 13(1):195. DOI:10.1186/1472-6882-13-195 · 2.02 Impact Factor
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    • "They are characterized by the possession of edible tubers that are rich in starch, some ions and vitamins. However, most of the yam tubers have to be cooked before consumption, in order to remove the toxic compounds present [19], [20]. "
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    ABSTRACT: A 70-kDa galactose-specific lectin was purified from the tubers of Dioscorea opposita cv. nagaimo. The purification involved three chromatographic steps: anion exchange chromatography on a Q-Sepharose column, FPLC-anion exchange chromatography on a Mono Q column, and FPLC-gel filtration on a Superdex 75 column. The purified nagaimo lectin presented as a single 35-kDa band in reducing SDS-PAGE while it exhibited a 70-kDa single band in non-reducing SDS-PAGE suggesting its dimeric nature. Nagaimo lectin displayed moderate thermostability, retaining full hemagglutinating activity after heating up to 62°C for 30 minutes. It also manifested stability over a wide pH range from pH 2 to 13. Nagaimo lectin was a galactose-specific lectin, as evidenced by binding with galactose and galactose-containing sugars such as lactose and raffinose. The minimum concentration of galactose, lactose and raffinose required to exert an inhibitory effect on hemagglutinating activity of nagaimo lectin was 20 mM, 5 mM and 40 mM, respectively. Nagaimo lectin inhibited the growth of some cancer cell lines including breast cancer MCF7 cells, hepatoma HepG2 cells and nasopharyngeal carcinoma CNE2 cells, with IC(50) values of 3.71 µM, 7.12 µM and 19.79 µM, respectively, after 24 hour treatment with nagaimo lectin. The induction of phosphatidylserine externalization and mitochondrial depolarization indicated that nagaimo lectin evoked apoptosis in MCF7 cells. However, the anti-proliferative activity of nagaimo lectin was not blocked by application of galactose, signifying that the activity was not related to the carbohydrate binding specificity of the lectin.
    PLoS ONE 01/2013; 8(1):e54212. DOI:10.1371/journal.pone.0054212 · 3.23 Impact Factor
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