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Mouse Single Oral Dose Toxicity Test of Lonicerae Flos Aqueous Extracts  

Yoo, Hyo-Jeong (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University)
Park, Mee-Yeon (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University)
Choi, Hae-Yun (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University)
Kim, Jong-Dae (Dept. of Internal Medicine, College of Oriental Medicine, Dae-Gu Haany University)
Publication Information
The Journal of Internal Korean Medicine / v.31, no.3, 2010 , pp. 539-553 More about this Journal
Abstract
Objectives : The object of this study was to obtain accurate information (single oral dose toxicity) of Lonicerae Flos (LF; Dried flower bud parts of Lonicera japonica Thunb (Caprifoliaceae)), which has traditionally been used in Korean medicine for treating various inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of LF aqueous extracts with organ weights and histopathological observations of 12 types of principle organs. Results : 1. After single oral treatment of LF aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. 2. Slight diarrhea was detected in most mice treated with 2,000 mg/kg of LF aqueous extracts and male mice of LF aqueous extracts 1,000 mg/kg within 2 days after end of treatment, respectively. Conclusion : The results obtained in this study suggest that the LD 50 and ALD of LF aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 mg/kg of LF aqueous extracts were administered in the present study.
Keywords
Lonicerae Flos; Toxicity;
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Times Cited By KSCI : 11  (Citation Analysis)
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1 U.S. Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.10 0, Acute Toxicity Testing Background. US EPA August, Washington, USA, 1998.
2 조성구. 金銀花添加가 肉鷄生産性과 臟器發育에 미치는 影響. 韓國家禽學會誌. 1992;19:27-34.
3 김동현, 김형민, 류종훈, 엄재영, 김상찬, 양재하, 조민경, 임종필, 홍승헌. 한방약리학. 서울: 신일상사; 2006. p. 133-5.
4 Chang, W.C., Hsu, F.L. Inhibition of platelet activation and endothelial cell injury by polyphenolic compounds isolated from Lonicera japonica Thunb. Prostaglandins Leukot Essent Fatty Acids. 1992; 45:307-12.   DOI   ScienceOn
5 Tang, D., Li, H.J., Chen, J., Guo, C.W., Li, P.. Rapid and simple method for screening of natural antioxidants from Chinese herb Flos Lonicerae Japonicae by DPPH-HPLC-DADTOF/MS. J. Sep. Sci.. 2008;31:3519-26.   DOI   ScienceOn
6 Wang, T., Jiang, X., Yang, L., Wu, S.. pH-gradient counter-current chromatography isolation of natural antioxidant chlorogenic acid from Lonicera japonica Thumb. using an upright coil planet centrifuge with three multi-layer coils connected in series. J. Chromatogr. A.. 2008;1180:53-58.   DOI   ScienceOn
7 Plata, E.J., Murphy, W.H., Growth and haematologic properties of the BALB/wm strain of inbred mice. Lab. Anim. Sci., 1972;22:712-20.
8 Yamaguchi, C., Fujita, S., Obara, T., Ueda, T. Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp. Anim., 1983; 32:1-11.   DOI
9 Lee, H.S., Lee I.G., Ku S.K.. Single oral dose toxicity study of water extracts of Picrorrhiza Rhizoma in mice. J. Toxicol. Pub. Health. 2006; 22:117-26.   과학기술학회마을
10 Lee, J.H, Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Lee, H.S., Ku, S.K.. Single subcutaneous dose toxicity of $Polycan{\circledR}$, a $\beta$-glucan originated from Aureobasidium in mice. Lab. Anim. Res.. 2005;21:299-305.
11 Banks, W.J.,. Female reproductive system. In: Banks WJ (Ed). Applied veterinary histology, 2nd ed., Baltimore: Williams & Wilkins; 1986. p. 506-26.
12 Pineda, M.H. Female reproductive system. In: McDonald LE and Pineda MH (Eds). Veterinary endocrinology and reproduction, Lea & Febiger: Philadelphia. 1989. p. 303-54.
13 Yip, E.C., Chan, A.S., Pang, H., Tam, Y.K., Wong, Y.H.. Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c - Jun N - terminal kinase - dependent mechanism. Cell Biol. Toxicol. 2006; 22:293-302.   DOI   ScienceOn
14 박선관, 이은방, 최병기. 사염화탄소 유발 간독성에 대한 金銀花의 작용. 응용약물학회지. 2002; 10:32-6.   과학기술학회마을
15 김상찬, 이재령, 최경임, 박숙자, 권영규, 변성희. 金銀花화장수가 DNCB로 유발된 접촉성 피부염에 미치는 영향. 大韓本草學會誌. 2006; 21:9-15.
16 이정노, 정승일, 장선일. 수용성 金銀花추출물이 Trimellitic Anhydride 유도 마우스 접촉성 과민반응에 미치는 영향. 大韓本草學會誌. 2008; 23:51-8.   과학기술학회마을
17 배지현, 김미순, 강은혜. 식중독 유발세균의 증식에 미치는 金銀花추출물의 항균효과. 한국식품과학회지. 2005;37:642-7.   과학기술학회마을
18 Lee, J.H., Ko, W.S., Kim, Y.H., Kang, H.S., Kim, H.D., Choi, B.T.. Anti - inflammatory effect of the aqueous extract from Lonicera japonica flower is related to inhibition of NF - kappaB activation through reducing I - kappaBalpha degradation in rat liver. Int. J. Mol. Med. 2001;7:79-83.
19 Tae, J., Han, S.W., Yoo, J.Y., Kim, J.A., Kang, O.H., Baek, O.S., Lim, J.P., Kim, D.K., Kim, Y.H., Bae, K.H., Lee, Y.M.. Anti - inflammatory effect of Lonicera japonica in proteinase - activated receptor 2 - mediated paw edema. Clin. Chim. Acta.. 2003;330:165-71.   DOI   ScienceOn
20 Kim, J.A., Kim, D.K., Kang, O.H., Choi, Y.A., Park, H.J., Choi, S.C., Kim, T.H., Yun, K.J., Nah, Y.H., Lee, Y.M.. Inhibitory effect of luteolin on TNF - alpha - induced IL-8 production in human colon epithelial cells. Int. Immunopharmacol.. 2005;5:209-17.   DOI   ScienceOn
21 Suh, S.J., Chung, T.W., Son, M.J., Kim, S.H., Moon, T.C., Son, K.H., Kim, H.P., Chang, H.W., Kim, C.H.. The naturally occurring biflavonoid, ochnaflavone, inhibits LPS - induced iNOS expression, which is mediated by ERK1/2 via NF - kappaB regulation, in RAW264.7 cells. Arch. Biochem. Biophys. 2006;447:136-46.   DOI   ScienceOn
22 Luo, Z.H. The combined modulating effects of cerium nitrate with certain Chinese traditional drugs on altered cell-mediated immunities in scald mice. Zhonghua Wai Ke Za Zhi. 1990; 28:562-5, 574-5.
23 Ryu JC, Kim KR, Kim HJ, Youn JY, Myung SW, Kim GH, Lee MJ, Chang IM. Genotoxicity study of bojungchisup-tang, an oriental herbal decoction-in vitro chromosome aberration assay in Chinese hamster lung cells and in vivo supravital -staining micronucleus assay with mouse peripheral reticulocytes. Arch Pharm Res. 1998;21:391-7.   DOI   ScienceOn
24 황석연 외 12인. 가미귀비탕의 4주 반복투여독성 평가. The korean journal of laboraty animal science. 2004;20(3):267-73.
25 배열철, 최빈혜, 김동우, 허진일, 변준석, 김대준. 보중익기탕합대칠기탕 추출물의 ICR 마우스에서 경구단회투여독성 평가. 대한한방내과학회. 2005;26(2):369-78.   과학기술학회마을
26 한국식품의약품안전청. 의약품 등의 독성시험기준. 서울: 한국식품의약품안전청 고시 제 2005-60호. 2005.
27 Organization for Economic C0-Operation and Development(Ed.). OECD guideline(423) for the testing of chemicals-acute oral toxicity-acute toxic class method. 2001.
28 Dourish CT. Effects of drugs on spontaneous motor activity. In: Experimental Psychopharmacology. Greenshaw AJ. and Dourish, CT. (Eds). Clifton: Humana Press. 1987. p. 325-34.
29 장인수, 양창섭, 이선동, 한창호. 최근 독성 문제가 제기된 한약에 대한 오해와 실제. 대한한방내과학회지. 2007;spr:67-75.
30 이은, 박병욱, 허금정, 고흥. 한약과 민간약물의 독성 및 부작용에 대한 고찰. 대한한방내과학회지. 2002;23(2):222-7.   과학기술학회마을
31 경희대학교 약학대학. 건강기능식품의 기능성 평가 체계 구축에 대한 연구. 서울: 식품의약품안전청; 2002.
32 Leung, H.W., Kuo, C.L., Yang, W.H., Lin, C.H., Lee, H.Z.. Antioxidant enzymes activity involvement in luteolin - induced human lung squamous carcinoma CH27 cell apoptosis. Eur. J. Pharmacol. 2006;534:12-8.   DOI   ScienceOn
33 Leung, H.W., Wu, C.H., Lin, C.H., Lee, H.Z.. Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis. Eur. J. Pharmacol. 2005;508:77-83.   DOI   ScienceOn
34 Park, E., Kum, S., Wang, C., Park, S.Y., Kim, B.S., Schuller - Levis. Anti - inflammatory activity of herbal medicines: inhibition of nitric oxide production and tumor necrosis factor - alpha secretion in an activated macrophage - like cell line. Am. J. Chin. Med. 2005;33:415-24.   DOI   ScienceOn
35 김인락, 김호철, 국윤범, 박성주, 박용기, 박지하, 서부일, 서영배, 송호준, 신민교, 이영종, 이영철, 이제현, 임강현, 조수인, 정종길, 주영승, 최호영. 本草學. 서울: 圖書出版永林社; 2007, p. 240-2.
36 Lee JE, Kim HJ, Choi EK, Chai HY. Yun YW, Kim DJ, Nam SY, Lee BJ, Ahn BW, Kang HG. and Kim, YB. Four-week repeated-dose toxicity study on Pinellia Extract. Korean J. Lab. Anim. Sci. 2003;19:127-41.
37 장인규, 홍남두. 죽력 (竹瀝)의 독성시험 및 약효학적 연구. 대한한방내과학회지. 1985;2:83-101.
38 Theoharides TC. Sudden death of a healthy college student related to ephedrine toxicity from a mahuang-containing drink. J. Clin Psychopharmacol. 1997;17:437-9.   DOI   ScienceOn
39 Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res. 2003;17:299-305.   DOI   ScienceOn
40 Chen J, Tong Y, Zhang X, Tian H, Chang Z. Acute toxicity of Stephania cepharantha. Zhong Yao Cai. 1999;22:468-9.
41 Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutr. 2000;3:473-85.
42 이혜정. 종류별 인삼수침엑기스의 독성 연구. 침구과학회지. 1993;10:167-73.
43 Chen H, Feng R, Guo Y, Sun L, Zhou Y, Jiang J. Toxicity studies of Rhizoma Polygonati Odorati. J Ethnopharmacol. 2001;74:221-4.   DOI   ScienceOn
44 황석연 외 12인. 상엽의 4주 반복투여독성 평가. The korean journal of laboratory animal science. 2004;20(3):274-82.
45 Ninomiya H, Kato S, Okuda H. Effects of Hachimi-jio-gan in aged rats. J Altern Complement Med. 2001;7:355-9.   DOI   ScienceOn
46 Ko, H.C., Wei, B.L., Chiou, W.F.. The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus - infected human epithelial cells. J. Ethnopharmacol. 2006;107: 205-10.   DOI   ScienceOn
47 Choi, C.W., Jung, H.A., Kang, S.S., Choi, J.S., Antioxidant constituents and a new triterpenoid glycoside from Flos Lonicerae. Arch. Pharm. Res. 2007;30:1-7.   과학기술학회마을   DOI   ScienceOn
48 Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia. 1968;13: 222-57.   DOI   ScienceOn