Genotoxicity studies on the root extract of Polygala tenuifolia Willdenow

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Highlights

  • The root extract of Polygala tenuifolia Willdenow did not increase the number of revertant colonies.

  • The extract did not cause chromosomal aberration in short-period test.

  • The extract did not increase in the frequency of micronucleated polychromatic erythrocytes.

Abstract

The root of Polygala tenuifolia Willdenow has been used for the treatment against insomnia, amnesia, depression, palpitations with anxiety, and memory improvement. However, there is no sufficient background information on toxicological evaluation of the root to given an assurance of safety for developing dietary supplements and functional foods. As part of a safety evaluation, the potential genotoxicity of the root extract of P. tenuifolia was evaluated using a standard battery of tests (bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay). In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, the extract did not increase the number of revertant colonies in any tester strain with or without metabolic activation by S9 mix, and did not cause chromosomal aberration in short-period test with the S9 mix or in the continuous (24 h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg/day showed no significant or dose dependent increase in the frequency of micronucleated polychromatic erythrocytes (PCE). These results indicate that ingesting the rot extract P. tenuifolia is not genotoxic at the proper dose.

Introduction

A number of medicinal plants have a long history of traditional use, and they have played many important roles for humans since the dawn of civilization (Pankaj et al., 2009), because medicinal herbs are used for the prevention and treatment of diseases (Firenzuoli and Gori, 2007, Wang et al., 2009). The use of herbal products as primary therapeutics or supplements for improving health-related conditions is popular worldwide (Seeff et al., 2001). Interestingly, medicinal plants have provided high opportunities for the development of herbal food products, dietary supplements, and functional foods (Chau and Wu, 2006). Recently, concerns have been raised over the lack of quality control and of scientific evidence for the efficacy and safety of these products (Firenzuoli and Gori, 2007, Rousseaux and Schachter, 2003). Especially, people become more interested in the food safety and well-being in recent years, so the demand for functional food from natural sources is increased (Lee et al., 2003), because medicinal plants have undesirable side effects (Chan and Cheung, 2000). In traditional oriental medicine, the root of Polygala tenuifolia Willdenow has been prescribed in Asia for thousands of years, because of its expectorant, tonic, tranquilizer, and antipsychotic properties (Spelman et al., 2006, Wang et al., 2007, Nagai and Suzuki, 2001, Klein et al., 2012, Jin et al., 2012). Previously, we reported that the root extract of P. tenuifolia can enhance memory and cognitive function in two animal models or two human models (Park et al., 2002, Lee et al., 2009, Shin et al., 2009a, Shin et al., 2009b) and the acute or subchronic toxicity of the root extract was not toxic to dogs and rats (Shin et al., 2014). Several researchers have demonstrated the effects of P. tenuifolia, but information on its safety is lacking. Therefore, systematic evaluation of the safety of the root extract of this herb is necessary for development of new foods or drugs. In this study, we evaluated the potential genotoxicity of the dried root extract of P. tenuifolia was conducted using the standard battery of tests recommended by OECD and the Korea Food and Drug Administration (KFDA). The test included the bacterial reverse mutation test (Ames test), the chromosomal aberrations test and the micronucleus tests to assure its safe use in dietary supplements or functional ingredients.

Section snippets

Extraction of Polygala tenuifolia

The dried root extract of P. tenuifolia (500 g) was refluxed with 75% ethanol for 4 h in a boiling water bath. This procedure was repeated twice and the ethanol solution was concentrated under vacuum. The concentrated ethanol fraction (125 g) of the plant root, obtained as described above, was used for this study (Park et al., 2002).

Bacterial mutation assay (Ames test)

The Ames test was carried out in according to the methods described in OECD (1997a) and the KFDA Notification No. 1999-61 (KFDA, 1999). Two strains of Salmonella

Bacterial mutation assay (Ames test)

There was neither increase of colonies nor cytotoxicity in S. typhimurium TA100, TA1535, TA98 and TA1573 at any dose level of test substance both in the presence and absence of metabolic activation system. In WP2 uvrA, there was neither increase of colonies nor cytotoxicity at any dose level of the test substance both in the presence and absence of metabolic activation system. The background lawn was also normal in all strains. There was significant increase in the number of colonies in all

Discussion

P. tenuifolia Willdenow is a perennial herbaceous plant distributed widely in China and Korea.

In particular, the root of the herb is used against insomnia, neurasthenia, amnesia, depression, palpitations with anxiety, restlessness, and disorientation, dementia, and memory failure (Huang, 1993, Liu et al., 2010). The extract has been shown to contain C-glycosides, triterpene saponins, sucrose esters, and oligosaccharide esters (Ikeya et al., 2004, Ling et al., 2013). It also contains various

Conflict of interests

The authors declare that there are no conflicts of interest.

Acknowledgements

This study was supported by SNUH-GLP (Non-Clinical Research Center, Biomedical Research Institute, Seoul National University Hospital) and Preclinical Research Center, ChemOn Inc., respectively.

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