Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity

Eun-Sun Hwang, Gun-Hee Kim, Eun-Sun Hwang, Gun-Hee Kim

Abstract

Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, α-cadinol, camphene, pinocarvone, β-caryophyllene, 3-cyclohexen-1-ol, and γ-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral single gavage administration of C. indicum flower oil. There were no mortality and clinical signs of toxicity at 2,000 mg/kg body weight/day of C. indicum flower oil throughout the 15 day period. Micronucleated erythrocyte cell counts for all treated groups were not significantly different between test and control groups. Levels of 15.63~500 μg C. indicum flower oil/plate did not induce mutagenicity in S. Typhimurium and E. coli, with or without the introduction of a metabolic activation system. These results indicate that ingesting C. indicum flower oil produces no acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation.

Keywords: Chrysanthemum indicum flower oil; acute oral toxicity; bacterial reverse mutation; bone marrow micronucleus.

Figures

Fig. 1
Fig. 1
Body weight changes for male and female rats after administered by C. indicum flower oil at 2,000 mg/kg body weight. Each value is expressed as mean±SD of measurement.

References

    1. Yu DO, Xie FZ, He WY, Liang XT. Application of 2D NMR techniques in the structure determination of chrysanthetriol. Acta Pharmaceutica Sinica. 1992;27:191–196.
    1. Matsuda H, Morikawa T, Toguchida I, Harima S, Yoshikawa M. Medicinal flowers. VI. absolute stereostructures of two new flavanone glycosides and a phenylbutanoid glycoside from the flowers of Chrysanthemum indicum L.: their inhibitory activities for rat lens aldose reductase. Chem Pharm Bull. 2002;50:972–975.
    1. Cheng W, Li J, You T, Hu C. Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linne. J Ethnopharmacol. 2005;101:334–337.
    1. Kim HG, Kim YE, Do JR, Lee YC, Lee BY. Antioxidative activity and physiological activity of some Korean medicinal plants. Korean J Food Sci Technol. 1995;27:80–85.
    1. Lee JH, Chang KM, Kim GH. Anti-inflammatory activities of Chopi (Zanthoxylum piperitum A.P. DC) essential oil: suppression of the inducible nitric oxide synthase and cellular adhesion. Food Sci Biotechnol. 2008;18:123–132.
    1. Shunying Z, Yang Y, Huaidong Y, Yue Y, Guolin Z. Chemical composition and antimicrobial activity of the essential oils of Chrysanthemum indicum. J Ethnopharmacol. 2005;96:151–158.
    1. Chang KM, Kim GH. Comparative chemical composition of domestic and imported Chrysanthemum indicum L. flower oils. Food Sci Biotechnol. 2009;18:1288–1292.
    1. Zhang C, Qin MJ, Shu P, Hong JL, Lu L, He DX. Chemical variations of the essential oils in flower heads of Chrysanthemum indicum L. from China. Chem Biodiver. 2010;7:2951–2962.
    1. Jiang H, Li F, Zeng S. Capillary GC determination of β-elemene, camphor and borneol in Chrysanthemum morifolium. Yaowu Fenxi Zazhi. 2005;25:508–511.
    1. Wang Y, Yang X. GC-MS analysis of essential oil of the flower of the Chrysanthemum morifolium by the different processing methods. Zhongguo Zhongyao Zazhi. 2006;31:456–459.
    1. Schmid W. Chemical mutagen testing on in vivo somatic mammalian cells. Agents Act. 1973;3:77–85.
    1. Heddle LA. A rapid in vivo test for chromosomal damage. Mutat Res. 1973;18:187–190.
    1. Suzuki Y, Nagashima T, Shimizu H. Occupational Health in the Chemical Industry. WHO Regional Office for Europe; Copenhagen, Denmark: 1998. Effects of carbon monoxide on the micronucleus test; pp. 156–166.
    1. Heddle JA, Gimino MC, Hayashi M, Romagna F. Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Mol Mutagen. 1991;18:277–291.
    1. Nagashima T, Okonogi H, Suzuki Y. Effects of anoxia on chromosomal aberration. Tokyo Jikeikai Med J. 1993;108:71–78.
    1. Guerin MR. Energy sources of polycyclic aromatic hydrocarbons. In: Gelboin HV, Ts’o POP, editors. Polycyclic Hydrocarbons and Cancer: Chemistry, Molecular Biology and Environment. Academic Press; New York, NY, USA: 1978. pp. 1–42.
    1. Miyamoto CT, Santanna JR, Franco CC, Castro-Prado MA. Genotoxicity (mitotic recombination) of the cancer chemotherapeutic agents’ cisplatin and cytosine arabinoside in Aspergillus indulans. Food Chem Toxicol. 2007;45:1091–1095.
    1. Han EH, Hwang YP, Jeong TC, Lee SS, Shin JG, Jeong HG. Eugenol inhibit 7,12-dimethylbenz[a]anthracene-induced genotoxicity in MCF-7 cells: Bifunctional effects on CYP1 and NAD(P)H: quinine oxidoreductase. FEBS Lett. 2007;581:749–756.
    1. Gomez NE, Witte L. A simple method to extract essential oils from tissue samples by using microwave radiation. J Chem Ecol. 2001;27:2351–2359.
    1. AAALAC international. Association for Assessment and Accreditation of Laboratory Animal Care. 1998. [accessed July 2006]. .
    1. Schmid W. The micronucleus test. Mutat Res. 1975;31:9–15.
    1. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983;113:173–215.
    1. OECD. OECD Principles on Good Laboratory Practice. Organization for Economic Cooperation and Development; 1997.
    1. OECD. TG No. 471 ‘Bacterial reverse mutation test’. Organization for Economic Cooperation and Development; 1997. Guidelines for the testing of chemicals.
    1. Sun J. D-Limonene: Safety and clinical applications. Alternative Med Rev. 2007;12:259–264.
    1. Turner SD, Tinwell H, Piegorsch W, Schmezer P, Ashby J. The male rat carcinogens limonene and sodium saccharine are not mutagenic to male big blue rats. Mutagen. 2001;16:329–332.

Source: PubMed

3
Subscribe