An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects.
OBJECTIVE
Renal fibrosis is central to progression of most chronic renal pathologies. Antioxidants that protect the tubular epithelium and anti-fibrotics that induce apoptosis of pro-fibrotic myofibroblasts without adversely affecting tubular epithelium may slow progression of renal fibrosis, while toxic substances may exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular epithelial cells (NRK52E) to determine their potential value as therapeutic agents in renal fibrosis involving oxidative stress.


METHODS
Herbs were chosen because of their traditional use in kidney or urinary system disorders, or because of recent published interest in their therapeutic or toxic potential in kidney disease. Extracts of herbs were made using a sequential multi-solvent extraction process. Each extract was analysed separately. Extraction solvents were ethyl acetate, methanol and 50% aqueous methanol. Cells were treated with extracts with/without oxidative stress (1.0 mM hydrogen peroxide). Cellular changes (apoptosis, necrosis, mitosis, transdifferentiation) were identified and quantified using defined criteria.


RESULTS
All extracts of Dioscorea villosa showed significant toxicity to both cell lines. At low concentrations (5-50 microg/mL) they induced epithelial to mesenchymal transdifferentiation, as demonstrated by increased immunohistochemistry staining for alpha-smooth muscle actin and transforming growth factor-beta1 in treated versus control cells. Angelica sinensis, Centella asiatica, Glycyrrhiza glabra, Scutellaria lateriflora, and Olea europaea demonstrated strong antioxidant effects in epithelial cells and/or apoptotic effects on fibroblasts.


CONCLUSIONS
This investigation has revealed renotoxicity of D. villosa and anti-fibrotic, oxidant potential of several herbal extracts, all of which require further study.
Wojcikowski
Ken
K
University of Queensland, Brisbane, Australia. kwojciko@scu.edu.au
Wohlmuth
Hans
H
Johnson
David W
DW
Rolfe
Margaret
M
Gobe
Glenda
G
D000199:Actins / Q000032:analysis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D007674:Kidney Diseases / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014570:Urologic Diseases / Q000188:drug therapy*
D000199:Actins; D010936:Plant Extracts; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat