Contents lists available at ScienceDirect Regulatory Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/yrtph Acute and sub-acute oral toxicity studies of standardized extract of Nasturtium officinale in Wistar rats M. Clemente ⁎ , M.D. Miguel, K.B. Felipe, C. Gribner, P.F. Moura, A.G.R. Rigoni, L.C. Fernandes, J.L.S. Carvalho, I. Hartmann, M.T. Piltz, R. Henneberg, D.P. Montrucchio, O.G. Miguel Federal University of Parana (UFPR), Brazil ARTICLE INFO Keywords: Standardized extract Nasturtium officinale Watercress Wistar rats and toxicological evaluation ABSTRACT Nasturtium officinale (watercress) is a perennial dicotyledonous plant, rich in vitamins, minerals and chemical compounds. The leaves of this plant, which contain glucosinolate, are used for its diuretic and hypoglycemic effects. The purpose of the study was to investigate the safety of the standardized extract of Nasturtium officinale (SENO) with phenylethyl glucosinolate 5.0 mg/ml -1 , using acute and sub-acute oral dosage in Wistar rats. High- Performance Liquid Chromatography (HPLC) analyzed the chemical composition, from aerial parts of water- cress. In the acute toxicity study, dose estimated was LD 50 in the range of 2000–5000 mg/kg, signs of mortality and toxicity on female rats were observed for 14 days, after single doses of 2000 and 5000 mg/kg. In the sub- acute study, female and male rats, age 10 weeks, were supplemented at doses of 250, 500 and 1000 mg/kg for 28 days. On the 29th day, rats were fasted, anesthetized, euthanized, then their blood used for hematological and biochemical evaluation. No significant changes in general behavior were reported regarding the acute study, while the sub-acute study demonstrated no toxicity of the hematopoietic and biochemical systems. The results showed that SENO at dosage up to 5000 mg/kg in acute study was safe, and NOAEL (no-observed-adverse-effect levels) in the sub-acute, was up to 1000 mg/kg. 1. Introduction The use of herbal medicines has increased progressively in many parts of the world, as a result of the popularity of complementary and alternative medicine, despite the lack or scarcity of data regarding safety, disposition, and efficacy (Chen et al., 2011). The safety and ef- fectiveness of these plants must be studied thoroughly to maximize their benefits for humankind (Almanc et al., 2011). According to (Ekor, 2014), the general perception that herbal medicines are very safe and devoid of adverse effects is not only untrue but also misleading. Plants have shown that they are capable of pro- ducing a wide range of undesirable or adverse effects, some of which can lead to serious injuries, life-threatening conditions, and even death. Watercress, or Nasturtium officinale R. Br, from the Brassicaceae fa- mily, contains a traditional composition of vitamins (A, C, and E) and minerals (manganese, iron, phosphorus, iodine, copper, and calcium). It is also rich in chemical compounds including flavonoids, polyphenols, glucosinolate, and phenylethyl isothiocyanate (PEITC), which is a breakdown product, via myrosinase, of glucosinolate such as gluco- nasturtiin (Justesen and Knuthsen, 2001) (Bahramikia and Yazdanparast, 2008)(Canistro et al., 2004). The leaves of this plant contain chemical compounds, especially glucosinolate, are used as home remedy medicines in popular culture by virtue of their depurative, diuretic, and expectorant effects. Therefore, they can be used in the treatment of stomachache, hypertension, dia- betes, as well as many other chronic diseases (Yazdanparast et al., 2008)(Bahramikia and Yazdanparast, 2008). Additionally, the com- mercialized preparation containing nasturtium (Tropaeolum majus), a different species from this present study, demonstrated effectiveness and safety in acute sinusitis, bronchitis and urinary tract infection (Goos et al., 2013). Although previous studies, on the potential therapeutic usefulness of Nasturtium Offcinale R. Br. have been conducted, no acute or sub- acute toxicological evaluation of this plant was reported in a standar- dized extract in terms of its constituents (marker compounds). In the literature it was found only acute toxicity test of ethanolic extract of https://doi.org/10.1016/j.yrtph.2019.104443 Received 14 April 2019; Received in revised form 5 August 2019; Accepted 14 August 2019 ⁎ Corresponding author. Rua Joaquim Caetano da Silva, 310- Santa Quiteria, Curitiba, Paraná, 80330-190, Brazil. E-mail addresses: mirnaclemente@yahoo.com (M. Clemente), dallarmi@ufpr.br (M.D. Miguel), karinabettega@ufpr.br (K.B. Felipe), carol_gribner@yhaoo.com.br (C. Gribner), paulafrancislaine19@gmail.com (P.F. Moura), ana.angelica@ufpr.br (A.G.R. Rigoni), lcfer@ufpr.br (L.C. Fernandes), fitoanalitica@hotmail.com (J.L.S. Carvalho), ivo.hartmann@ufpr.br (I. Hartmann), marinapiltz@yahoo.com.br (M.T. Piltz), railson@ufpr.br (R. Henneberg), deisepm@yahoo.com.br (D.P. Montrucchio), obdulio@ufpr.br (O.G. Miguel). Regulatory Toxicology and Pharmacology 108 (2019) 104443 Available online 19 August 2019 0273-2300/ © 2019 Elsevier Inc. All rights reserved. T