Volume 166, 26 May 2015, Pages 250–260
Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: Toxicological implications
Abstract
Ethnopharmacological relevance
Although acknowledged as toxic herbs, Aristolochia
species are still widely used worldwide. The aristolochic acids (AA)
they contain can induce the so-called “aristolochic acid nephropathy”,
leading to renal fibrosis and upper urinary tract cancer. Traditional
Moroccan medicine still often uses Aristolochia species under the vernacular name of Bereztem
for the treatment of numerous ailments, notably cancer, diabetes or
digestive tract disorders. As the botanical identity and renal toxicity
of used species remain unexplored, the safety of patients may be
threatened.
Material and methods
Ethnopharmacological
data were collected from herbalists from the provinces of Oujda and
Berkane, located in North-Eastern Morocco. Samples of Bereztem
were collected at herbalist shops and checked for their content in AA
using TLC and LC-MS methods. The toxicity of crude methanolic extracts
of each herb was assessed on a HK-2 cell-based in vitro model by measurement of the cell survival to evaluate cytotoxicity and by assessment of renal-specific toxicity via
(i) the evaluation of genes (E-cadherin and α-smooth muscle actin)
expression by RT-qPCR; (ii) the quantities of β-catenin and vimentin by
immunofluorescence microscopy; (iii) the secretion of fibronectin; and
(iv) the excretion of interleukin-6.
Results
The survey indicated that, among 42 herbalists visited, 33 were retailers of Bereztem, which was generally sold as a cancer treatment. Botanical investigations revealed that Aristolochia longa was frequently substituted by Bryonia dioica,
which was associated with a higher cytotoxicity. Parameters specific to
renal toxicity were also found to be enhanced, as compared to Aristolochia baetica and A. longa:
down-regulation of β-catenin and E-cadherin and up-regulation of
vimentin and α-smooth muscle actin, and secretion of fibronectin and
interleukin-6.
Conclusion
In accordance with the Moroccan regulations, the use of so-called Aristolochia
species should be discontinued. On one hand, the correctly identified
aristolochia contain nephrotoxic aristolochic acids; on the other hand,
aristolochia are massively substituted in North-Eastern Morocco and
adulterated by a well-known toxic herb, B. dioica. Our data
indicate that the bryony renal toxicity may be deleterious in shorter
time periods than aristolochia. Reinforced on-site controls are needed
to remind herbalists and harvesters that these herbs should be
prohibited.
Graphical abstract
Abbreviations
- AA, aristolochic acids;
- AAI, aristolochic acid I;
- AAII, aristolochic acid II;
- AAIV, aristolochic acid IV;
- α-SMA, α-smooth muscle actin;
- E-cadh, E-cadherin;
- ECM, extracellular matrix;
- EMT, epithelial-to-mesenchymal transition;
- IL-6, interleukin-6;
- RPTECs, renal proximal tubular epithelial cells.
Keywords
- Aristolochia baetica L.;
- Aristolochia longa L.;
- Bryonia dioica Jacq.;
- HK-2 cells;
- Misidentification;
- Toxicity
- Corresponding
author at: Laboratory of Experimental Nephrology, Campus Erasme, route
de Lennik 808, 1070 Brussels, Belgium. Tel./fax: +32 25556184/
+32 25556186 or +32 26505250/+32 26505430.
- 1
- Both authors contributed equally to this work and are displayed by alphabetical order.
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