Dioscorea villosa (wild yam) induces chronic kidney injury via pro-fibrotic pathways.
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.
Wojcikowski
Ken
K
School of Medicine, University of Queensland, Brisbane, Queensland, Australia. kwojciko@scu.edu.au
Wohlmuth
Hans
H
Johnson
David W
DW
Gobe
Glenda
G
D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D027742:Dioscorea / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D010936:Plant Extracts; D051547:Heme Oxygenase-1