[en] Ethnopharmacological relevance: In the 1990's, a Belgian cohort of more than 100 patients reported cases of Aristolochic Acid Nephropathy (AAN). This progressive renal and interstitial fibrosis, frequently associated with urothelial malignancies, was consecutive to the Chinese-herbs based slimming capsules intake where a plant Stephania tetrandra S. Moore was replaced by a highly genotoxic Aristolochia species. 70% of the Belgian patients evolved into end-stage renal disease, requiring dialysis or renal transplantation. Furthermore the prevalence of upper urinary tract carcinoma was found alarmingly high in these patients. The Aristolochia adulteration was blamed for the intoxication cases and, to the best of our knowledge, the prescription itself has not been further investigated.
Aim of the study: This work proposes to evaluate the in vitro cytotoxicity and genotoxicity of Aristolochia and Magnolia traditional aqueous decoctions and their association.
Materials and methods: The cytotoxicity of extracts has been assessed by a MTT cell proliferation assay and the genotoxicity by measuring the presence of γ-H2AX, a phosphorylated histone associated with DNA damages.
Results: Treating cells for 24h with a mixture 1:1 of Magnolia officinalis and Aristolochia baetica decoctions led to an increase in the production of γ-H2AX.
Conclusions: This genotoxic potentiation warrants further studies but may lead to an explanatory factor for the 'Chinese herb nephropathy' cases.
Disciplines :
Pharmacy, pharmacology & toxicology Chemistry
Author, co-author :
Nachtergael, Amandine ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie thérapeutique et Pharmacognosie
Poivre, Mélanie ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie thérapeutique et Pharmacognosie
Belayew, Alexandra ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Duez, Pierre ; Université de Mons > Faculté de Médecine et de Pharmacie > Chimie thérapeutique et Pharmacognosie
Language :
English
Title :
In vitro genotoxicity tests point to an unexpected and harmful effect of a Magnolia and Aristolochia association
Publication date :
13 August 2015
Journal title :
Journal of Ethnopharmacology
ISSN :
0378-8741
Publisher :
Elsevier, Switzerland
Volume :
174
Pages :
178-186
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M122 - Biochimie métabolique et moléculaire M136 - Chimie thérapeutique et Pharmacognosie
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
H. Achenbach, and A. Fischer 6-O-β-d-glucoside of aristolochic acid IIIa and other components from the roots of Aristolochia baetica Planta Med. 63 06 1997 579
H. Achenbach, and A. Fischer Aristolochic acids and aristolactams from the seeds of Aristolochia baetica Planta Med. 63 04 1997 387
F. Afaq Natural agents: cellular and molecular mechanisms of photoprotection Arch. Biochem. Biophys. 508 2 2011 144 151
S. Arora, S. Singh, and et al. Honokiol: a novel natural agent for cancer prevention and therapy Curr. Mol. Med. 12 10 2012 1244
S. Aydin, A.-F. Dekairelle, and et al. Unambiguous detection of multiple TP53 gene mutations in AAN-associated urothelial cancer in Belgium using laser capture microdissection PLoS One 9 9 2014 e106301: 2014 e106301
D. Bensky, S. Clavey, and et al. Chinese Herbal Medicine: Materia Medica 2004 Eastland Press Seattle, USA
N. Billinton, P.W. Hastwell, and et al. Interlaboratory assessment of the Green Screen HC GADD45a-GFP genotoxicity screening assay: an enabling study for independent validation as an alternative method Mutat. Res. 653 1-2 2008 23 33
L. Bonfili, M. Amici, and et al. Wheat sprout extract-induced apoptosis in human cancer cells by proteasomes modulation Biochimie 91 9 2009 1131 1144
D.F. Coutinho Moraes, D.W. Still, and et al. DNA-based authentication of botanicals and plant-derived dietary supplements: where have we been and where are we going? Planta Med. 81 09 2015 687 695
W. Cui, Y. Wang, and et al. Magnolia extract (BL153) ameliorates kidney damage in a high fat diet-induced obesity mouse model Oxidative Med. Cell. Longev. 2013 2013 9
F.D. Debelle, J.-L. Vanherweghem, and et al. Aristolochic acid nephropathy: a worldwide problem Kidney Int. 74 2 2008 158 169
J.S. Dickey, C.E. Redon, and et al. H2AX: functional roles and potential applications Chromosoma 118 6 2009 683 692
P. Duez, M. Hanocq, and et al. Photodynamic DNA damage mediated by δ-aminolevulinic acid-induced porphyrins Carcinogenesis 22 5 2001 771 778
EMEA, 2008. Overview of comments received on draft 'guideline on the assessment of genotoxic constituents in herbal substances/preparations. European Medicines Agency, London. emea/hmpc/107079/2007.
Z.-Z. Fang, Y.-Y. Zhang, and et al. Bioactivation of herbal constituents: simple alerts in the complex system Expert Opin. Drug Metab. Toxicol. 7 8 2011 1 19
L.E. Fried, and J.L. Arbiser Honokiol, a multifunctional antiangiogenic and antitumor agent Antioxid. Redox Signal. 11 5 2009 1139 1148
L.S. Gold, and T.H. Slone Aristolochic acid, an herbal carcinogen, sold on the Web after FDA alert N. Engl. J. Med. 349 16 2003 1576 1577
A.P. Grollman, S. Shibutani, and et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy Proc. Natl. Acad. Sci. 104 29 2007 12129 12134
B. Hazra, S. Ghosh, and et al. The prospective role of plant products in radiotherapy of cancer: a current overview Front. Pharmacol. 2 2012 1 13
M. Heinrich, J. Chan, and et al. Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2 - a global assessment based on bibliographic sources J. Ethnopharmacol. 125 1 2009 108 144
J.-R. Ioset, G. Raoelison, and et al. Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens Food Chem. Toxicol. 41 1 2003 29 36
J. Kanwar, and R. Kanwar Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal BMC Immunol. 10 1 2009 7
L.J. Kuo, and L.-X. Yang γ-H2AX - a novel biomarker for DNA double-strand breaks In Vivo 2008 22
Y.-J. Lee, Y.M. Lee, and et al. Therapeutic applications of compounds in the Magnolia family Pharmacol. Ther. 130 2 2011 157 176
Y.J. Lee, D.Y. Choi, and et al. Inhibitory effect of ethanol extract of Magnolia officinalis on memory impairment and amyloidogenesis in a transgenic mouse model of Alzheimer's disease via regulating β-secretase activity Phytother. Res. 26 12 2012 1884 1892
D.M. Mudie, K. Murray, and et al. Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state Mol. Pharm. 11 9 2014 3039 3047
A. Muslimovic, I.H. Ismail, and et al. An optimized method for measurement of gamma-H2AX in blood mononuclear and cultured cells Nat. Protoc. 3 7 2008 1187 1193
J. Nortier, M.-C. Martinez, and et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi) N. Engl. J. Med. 342 2000 1686 1692
M. Ouedraogo, T. Baudoux, and et al. Review of current and "omics" methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms J. Ethnopharmacol. 140 3 2012 492 512
M. Podhorecka, A. Skladanowski, and et al. H2AX phosphorylation: its role in DNA damage response and cancer therapy Nucl. Acids Res. 2011 2011 9 920161
S. Purup, E. Larsen, and et al. Differential effects of falcarinol and related aliphatic C17-polyacetylenes on intestinal cell proliferation J. Agric. Food Chem. 57 18 2009 8290 8296
H.H. Schmeiser, J.L. Nortier, and et al. Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy Int. J. Cancer 135 2 2014 502 507
K.M. Siddiqui, and D.P. Chopra Primary and long term epithelial cell cultures from human fetal normal colonic mucosa In Vitro 20 11 1984 859 868
V.S. Sidorenko, S. Attaluri, and et al. Bioactivation of the human carcinogen aristolochic acid Carcinogenesis 35 8 2014 1814 1822
V.S. Sidorenko, J.-E. Yeo, and et al. Lack of recognition by global-genome nucleotide excision repair accounts for the high mutagenicity and persistence of aristolactam-DNA adducts Nucl. Acids Res. 40 6 2012 2494 2505
D.J. Smart, K.P. Ahmedi, and et al. Genotoxicity screening via the γH2AX by flow assay Mutat. Res. 715 2011 25 31
H.S. Smith In vitro properties of epithelial cell lines established from human carcinomas and nonmalignant tissue J. Natl. Cancer Inst. 62 2 1979 225 230
M. Stiborová, E. Frei, and et al. Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase Carcinogenesis 24 10 2003 1695 1703
M. Stiborová, J. Mareîs, and et al. The human carcinogen aristolochic acid i is activated to form DNA adducts by human NAD(P)H:quinone oxidoreductase without the contribution of acetyltransferases or sulfotransferases Environ. Mol. Mutagen. 52 6 2011 448 459
V. Valdiglesias, S. Giunta, and et al. γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies Mutat. Res. 753 1 2013 24 40
J.L. Vanherweghem, C. Tielemans, and et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs Lancet 341 8842 1993 387 391
L. Verschaeve, J. Juutilainen, and et al. In vitro and in vivo genotoxicity of radiofrequency fields Mutat. Res.: Rev. Mutat. Res. 705 3 2010 252 268
G.P. Watters, D.J. Smart, and et al. H2AX phosphorylation as a genotoxicity endpoint Mutat. Res. 679 1-2 2009 50 58
WHO, 2002. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. Numéro 82 de IARC monographs on the evaluation of carcinogenic risks to humans. International Agency for Research on Cancer. IARC Press. ISSN 1017-1606. W. H. Organization.
E.M. Williamson, K. Chan, and et al. Evaluating the safety of herbal medicines: integrated toxicological approaches Science 347 6219 Suppl 2015 S47 S49
Q. Xu, R. Bauer, and et al. The quest for modernisation of traditional Chinese medicine BMC Complement. Altern. Med. 13 1 2013 132
J. Zhou, M. Ouedraogo, and et al. Potential genotoxicity of traditional Chinese medicinal plants and phytochemicals: an overview Phytother. Res. 27 12 2013 1745 1755