Toxicity of Aristolochia decoction: a relevant herbal in folk medicine

Authors

  • Victor Ventura de Souza UFPE
  • Micheli Sossai Spadeto
  • Roselena Abreu Guedes
  • Wellington Ronildo Clarindo
  • Carlos Roberto de Carvalho
  • Juliana Aparecida Severi
  • Tatiana da Silva Souza

DOI:

https://doi.org/10.13128/caryologia-880

Keywords:

Aristolochic acid, cytogenotoxicity, flow cytometry, heteropycnotic nuclei, Allium cepa test

Abstract

Ethnopharmacology studies report the use of Aristolochia (Aristolochiaceae) species as medicinal plants in various parts of the world. However, the acids aristolochic (AAs), secondary metabolites present in all species of Aristolochia, have cytogenotoxic activity and they are a potent carcinogen to rodents and humans. The aim of the current research was to perform to initial screening for the toxicity of Aristolochia labiata and Aristolochia triangularis decoctions through germination and growth rate, flow cytometry, mitotic index and cytogenetics analysis in Allium cepa. The decoctions were prepared from 2, 4, 8, 16 and 32 g L-1. Decoctions at concentrations 4 g to 16 g L-1 significantly reduced the germination rate of Allium cepa. Seeds exposed to 32 g L-1 decoctions did not germinate. All decoctions reduced the growth rate of onion seedlings. Decoctions at 4 g L-1 to 16 g L-1 inhibited mitotic index. Highest concentrations of decoctions (8 g L-1 and 16 g L-1 for Aristolochia labiata; 16 g L-1 for Aristolochia triangularis) showed statistically significant increase in frequency of Allium cepa nuclei in the G0/G1 phase. Both decoctions induced the formation of heteropycnotic nuclei. Qualitative phytochemical prospecting of decocts were performed and alkaloids secondary compounds were the largest presence in both species, indicating that the AAs may be related to the observed toxicity. Caution is recommended in the consumption of decoctions from Aristolochia labiata and Aristolochia triangularis stems. 

References

Akinboro A, Bakare AA. 2007. Cytotoxic and genotoxic effects of aqueous extracts of five medicinal plants on Allium cepa Linn. Journal of Ethnopharmacology 112, 470–475.

Albuquerque UP, Medeiros PM, Almeida ALS, Monteiro JM, Neto EMFL, Melo JG, Santos JP. 2007. Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: a quantitative approach. Journal of Ethnopharmacology 114, 325–354.

Amat GA, Yajia EM, Gonzalez CF, Lorca GL, Sanchez-Gonzalez F, Riglo AG, Veron JR. 2002. Evaluation of cytological parameters induced by aqueous extracts of seven plants used as antihypertensive agents in argentine folk medicine. Acta. Farmacéutica Bonaerense 21, 37-42.

Andrade-Vieira LF, de Campos JMS, Davide LC. 2012. Effects of Spent Pot Liner on mitotic activity and nuclear DNA content in meristematic cells of Allium cepa. Journal of Environmental Management 107, 140-146.

Araujo JL, Lemos JR. 2015. Estudo etnobotânico sobre plantas medicinais na comunidade de Curral Velho, Luís Correia, Piauí, Brasil. Biotemas 28, 125-136.

Baličević R, Ravlić M, Mišić M, Mikić, I. 2015. Allelopathic effect of Aristolochia clematitis L. Proceedings. 50th Croatian and 10th International Symposium on Agriculture. Opatija, Croatia, 54–58.

Bolson M, Hefler SR, Chaves EID, Gasparotto Junior AG, Cardozo Junior, EL. 2015. Ethno-medicinal study of plants used for treatment of human ailments, with residents of the surrounding region of forest fragments of Paraná, Brazil. Journal of Ethnopharmacology 161, 1–10.

Brasil. Política Nacional de Plantas Medicinais e Fitoterápicos, 2006. 〈http://portalsaude.saude.gov.br〉 (accessed May, 2019).

Bunel V, Antoine MH, Stévigny C, Nortier J, Duez P. 2016. New in vitro insights on a cell death pathway induced by magnolol and honokiol in aristolochic acid tubulotoxicity. Food and Chemical Toxicology 87, 77-87.

Chang HR, Lian JD, Lo CW, Huang HP, Wang CJ. 2007. Aristolochic acid-induced cell cycle G1 arrest in human urothelium SV-HUC-1 cells. Food and Chemical Toxicology 45, 396-402.

Citterio S, Aina R, Labra M, Ghiani A, Fumagalli P, Sgorbati S, Santagostino A. 2002. Soil genotoxicity assessment: a new strategy based on biomolecular tools and plant bioindicators. Environmental Science & Technology 36, 2748-2753.

Dias FL, Takahashi CS 1994. Cytogenetic evaluation of the effect of aqueous extracts of the medicinal plants Alpinia nutans Rose (Zingiberaceae) and Pogostemun heyneanus Benth (Labiatae) on wistar rats and Allium cepa Linn (Liliaceae) root tip cells. Revista Brasileira de Genética 17, 175-180.

Fachinetto JM, Bagatini MD, Durigon J, Silva ACF, Tedesco SB. 2007. Efeito anti-proliferativo das infusões de Achyrocline satureioides DC (Asteraceae) sobre o ciclo celular de Allium cepa. Revista Brasileira de Farmacognosia 17, 49-54.

Fiskesjö G. 1985. The Allium test as a standard in the environmental monitoring. Hereditas 102, 99-112.

Gatti AB, Perez SCJGA, Lima MIS, 2004. Atividade alelopática de extratos aquosos de Aristolochia esperanzae O. Kuntze na germinação e no crescimento de Lactuca sativa L. e Raphanus sativus L. Acta Botanica Brasilica 18, 459-472.

Grant WF. 1982. Chromosome aberration assays in Allium cepa. Mutation Research 99, 273-291.

Heinrich M, Chana J, Wanke S, Neinhuis C, Simmonds MSJ. 2009. Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2—A global assessment based on bibliographic sources Journal of Ethnopharmacology 125, 108–144

Hwang YH, Kim T, Cho WK, Yang HJ, Kwak DH, Ha H, Song KH, Ma JY. 2012. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom. Evidence-Based Complementary and Alternative Medicine 2012, 1-9.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. IARC Monogr
Eval Carcinog Risks Hum 82:1-556, 2002.

Jayat C, Ratinaud MH. 1993. Cell cycle analysis by flow cytometry: principles and applications. Biolology of the Cell 78, 15-25.

Junqueira L.C.; Carneiro, J. Biologia celular e Molecular, 2012. 9 Ed. Rio de Janeiro: Guanabara Koogan, 376p.

Leme DM, Angelis DF, Marin-Morales MA. 2008. Action mechanisms of petroleum hydrocarbons present in waters impacted by an oil spill on the genetic material of Allium cepa root cells. Aquatic Toxicology 88, 214–219.

Levin S, Bucci TJ, Cohen SM, Fix AS, Hardisty JF, Legrand EK, Maronpot RR, Trump BF. 1999. The nomenclature of cell death: recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists. Toxicologic Pathology 27, 484–90.

Li Y, Liu Z, Guo X, Shu J, Chen Z, Li L. 2006. Aristolochic acid I-induced DNA damage and cell cycle arrest in renal tubular epithelial cells in vitro. Archives of Toxicology 80, 524–532.

Li C, Wang MH. 2013. Aristolochia debilis Sieb. et Zucc. induces apoptosis and Reactive Oxygen Species in the HT-29 human colon cancer cell line. Cancer Biotherapy and Radiopharmaceuticals 28, 717-724.
Li W, Chan CK, Wong YL, Chan KJ, Chan HW, Chan W. 2018. Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains. Food chemistry, 264, 270-276.

Macedo MFS, Herbert AACN, Queiroz JDF, Argolo ACC, Saturnino ACRD, Coelho LCBB, Medeiros SRB. 2008. Determining the genotoxicity of an aqueous infusion of Bauhinia monandra leaves. Revista Brasileira de Farmacognosia 18, 509-516.

Manjo G, Joris I. 1995. Apoptosis, oncosis, and necrosis. An overview of cell death. American Journal of Pathology 146, 3–15.

Matos FJA. 1997. Introdução à fitoquímica experimental, Fortaleza. UFC (Eds), 1, pp. 44-46.

Mendes SS, Andrade JA, Xavier MA, Secundo Junior JA, Pantaleão SM, Estevam CS, Ferrari SF. 2012. Genotoxicity test of Maytenus rigida and Aristolochia birostris in the radicular meristem of the onion, Allium cepa. Revista Brasileira de Farmácia 22, 76-81.

Meneguetti DUO, Lima RA, Silva JB, Silva RP, Pagotto R, Facundo VA. 2014. Análise citotóxica e mutagênica do extrato aquoso de Maytenus guyanensis Klotzsch Ex Reissek (Celastraceae) Chichuá (Xixuá) amazônico. Ciência e Natura 36, 31-39.

Michl J, Jennings HM, Kite GC, Ingrouille MJ, Simmonds MSJ, Heinrich M. 2013. Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical–phytochemical approach. Journal of Ethnopharmacology 149, 235–244.

Monteiro MS, Rodriguez E, Loureiro J, Mann RM, Soares AMVM, Santos C. 2010. Flow cytometric assessment of Cd genotoxicity in three plants with different metal accumulation and detoxification capacities. Ecotoxicology and Environmental Safety 73, 1231-1237.

Murashige T, Skoog F. 1962. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiologia Plantarum 15, 473–497.

Neinhuis C, Wanke S, Hilu KW, Müller K, Borsch T. 2005. Phylogeny of Aristolochiaceae based on parsimony, likelihood and Bayesian analyses of trnL-trnF sequences. Plant Systematics and Evolution 250, 7–26.

Oloyede A, Okpuzor J, Omidiji O. 2009. Cytological and toxicological properties of a decoction used for managing tumors in Southwestern Nigeria. Pakistan Journal of Biological Sciences 12, 383-387.

O'Neil MJ. 2001. Solubility: Slightly soluble in water; soluble in acetic acid, acetone, aniline, alkalis, chloroform, diethyl ether and ethanol; practically insoluble in benzene and carbon disulfide The Merck Index, 13th Ed., Whitehouse Station, NJ, Merck & Co., pp. 48, 134.

Pacheco AG, Oliveira PM, Piló-Veloso D, Alcântara AFC. 2009. 13C-NMR Data of diterpenes isolated from Aristolochia species. Molecules 14, 1245-1262.

Pelayo HR, Pincheira J, Giménez-Abián1 JF, Clarke DJ, De La Torre C. 2003. p53-Independent checkpoint controls in a plant cell model. Biological Research 36, 381-388.

Piesik D, Pánka D, Dalaney KJ, Skoczek A, Lamarski R, Weaver DK. 2011. Cereal crop volatile organic compound induction after 22 mechanical injury, beetle herbivory (Oulema spp.), or fungal infection (Fusarium spp.). Journal of Plant Physiology 168, 878 – 886.

Rank J, Nielsen MH. 1994. Evaluation of the Allium anaphase-telophase test in relation to genotoxicity screening of industrial wastewater. Mutation Research 312, 17-24.

Sborchia M, De Prez EG, Antoine MH, Bienfait L, Indra R, Valbuena G, Arlt VM. 2019. The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro. Archives of toxicology, 93(11), 3345-3366.

Schmeiser HH, Bieler CA, Arlt VM, Stiborova M, Wiessler M. 2001. Ingredients of Aristolochia plants are risk factors for cancer. Research Report 1999/2000, DFKZ (German Cancer Research Centre), Heidelberg, p. 135-136.

Silva IM. 2008. A etnobotânica e a medicina popular em mercados na cidade do Rio de Janeiro. Thesis, Escola Nacional de Botânica Tropical, do Instituto de Pesquisas Jardim Botânico do Rio de Janeiro, Rio de Janeiro.

Silva TCR, Abreu IS, Carvalho CR. 2010. Improved and reproducible flow cytometry methodology for nuclei isolation from single root meristem. Journal of Botany 2010, 1-7.
Simões CMO, Mentz LA, Schenkel EP. Plantas da medicina popular no Rio Grande do Sul. Porto Alegre: Editora da Universidade,1995, p.173.

Slade N, Mollc UM, Brdar B, Zoric A, Kovi B. 2009. p53 mutations as fingerprints for aristolochic acid – an environmental carcinogen in endemic (Balkan) nephropathy. Mutation Research 663, 1–6.

Vicentini VEP, Camparoto ML, Teixeira RO, Mantovani MS. 2001. Averrhoa carambola L., Syzygiumcumini (L.) Skeels and Cissussicyoides L.: medicinal herbal tea effects on vegetal and test systems. Acta Scientiarum 23, 593-598.

Watanabe K, Miyakado M, Iwai T, Izumi K, Yanagi K. 1988. Isolation of aristolochic acid and aristolic acid from Cocculus triolobus DC as potent seed germination inhibitors. Agricultural and Biological Chemistry 52, 1079-1082.

WHO - World Health Organization/UNICEF. Primary health care: report of the International Conference on Primary Health Care, Alma-Ata, URSS, 1978. Geneva, 1978. p. 61.

Wu TS, Damu AG, Su CR, Kuo PC. 2005. Chemical constituents and pharmacology of Aristolochia species. In: Attaur-Rahman, editor. Studies in natural product chemistry (bioactive natural proudcts), vol. 32. Amsterdam: Elsevier; pp. 855–1018.

Yamani A, Bunel V, Antoine MH, Husson C, Stévigny C, Duez P, Elachouri M. Nortier, J., 2015. Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: Toxicological implications. Journal of Ethnopharmacology 166, 250–260.

Youl EN, Husson C, El Khattabi C, El Mere S, Declèves AE, Pochet S, Antoine MH. 2020. Characterization of cytotoxic effects of aristolochic acids on the vascular endothelium. Toxicology in Vitro, 104811.

Downloads

Published

2021-04-16

How to Cite

Ventura de Souza, V., Micheli Sossai Spadeto, Roselena Abreu Guedes, Wellington Ronildo Clarindo, Carlos Roberto de Carvalho, Juliana Aparecida Severi, & Tatiana da Silva Souza. (2021). Toxicity of Aristolochia decoction: a relevant herbal in folk medicine. Caryologia. International Journal of Cytology, Cytosystematics and Cytogenetics, 73(3). https://doi.org/10.13128/caryologia-880

Issue

Section

Articles