본문 바로가기
KERD
논문KCI 등재

金銀花 추출물의 마우스 단회 경구투여 독성실험

Mouse Single Oral Dose Toxicity Test of Lonicerae Flos Aqueous Extracts

0

조회

0

다운로드

7

인용

0

참고문헌

키워드

주제분류한의학

초록

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) ㎎/㎏ (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 ㎎/㎏ 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 ㎎/㎏ of LF aqueous extracts and male mice of LF aqueous extracts 1,000 ㎎/㎏ 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 ㎎/㎏ because no mortalities were detected up to 2000 ㎎/㎏, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 ㎎/㎏ of LF aqueous extracts were administered in the present study.

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) ㎎/㎏ (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 ㎎/㎏ 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 ㎎/㎏ of LF aqueous extracts and male mice of LF aqueous extracts 1,000 ㎎/㎏ 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 ㎎/㎏ because no mortalities were detected up to 2000 ㎎/㎏, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 ㎎/㎏ of LF aqueous extracts were administered in the present study.

참고문헌 (48)

  1. 김인락, "本草學", pp.240~242 (2007), 圖書出版 永林社
  2. 이지은, "반하의 4주 반복투여독성 평가", Laboratory Animal Research, 19(3), pp.127~141 (2003), 한국실험동물학회
  3. 장인규, "죽력 (竹瀝)의 독성시험 및 약효학적 연구", 대한한방내과학회지, 2, pp.83~101 (1985)
  4. Theoharides TC, "Sudden death of a healthy college student related to ephedrine toxicity from a mahuang-containing drink", J. Clin Psychopharmacol, 17, pp.437~439 (1997)
  5. Ali BH, "Pharmacological and toxicological properties of Nigella sativa", Phytother Res., 17, pp.299~305 (2003)
  6. Chen J, "Acute toxicity of Stephania cepharantha", Zhong Yao Cai, 22, pp.468~469 (1999)
  7. Kitts D, "Efficacy and safety of ginseng", Public Health Nutr, 3, pp.473~485 (2000)
  8. 이혜정, "종류별 인삼수침엑기스의 독성 연구", 침구과학회지, 10, pp.167~173 (1993)
  9. Chen H, "Toxicity studies of Rhizoma Polygonati Odorati", Ethnopharmacol., 74, pp.221~224 (2001)
  10. 김윤배, "상엽의 4주 반복투여독성 평가", Laboratory Animal Research, 20(3), pp.274~282 (2004), 한국실험동물학회
  11. Ninomiya H, "Effects of Hachimi-jio-gan in aged rats", J Altern Complement Med, 7, pp.355~359 (2001)
  12. Ryu JC, "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., 21, pp.391~397 (1998)
  13. 김윤배, "가미귀비탕의 4주 반복투여독성 평가", Laboratory Animal Research, 20(3), pp.267~273 (2004), 한국실험동물학회
  14. 배영철, "補中益氣合大七氣湯 추출물의 ICR 마우스에서 경구 단회투여독성 평가", 대한한방내과학회지, 26(2), pp.369~378 (2005), 대한한방내과학회
  15. 한국식품의약품안전청, "의약품 등의 독성시험기준", 한국식품의약품안전청 고시 제 2005- 60호, ~ (2005)
  16. Organization for Economic C0-Operation and Development, "OECD guideline(423) for the testing of chemicals-acute oral toxicity-acute toxic class method", ~ (2001)
  17. Irwin S, "Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse", Psychopharmacologia, 13, pp.222~257 (1968)
  18. Dourish CT, "Effects of drugs on spontaneous motor activity. In: Experimental Psychopharmacology", pp.325~334 (1987), Humana Press
  19. 장인수, "최근 독성 문제가 제기된 한약에 대한 오해와 실제", 대한한방내과학회지, pp.67~75 (2007)
  20. 이은, "한약과 민간약물의 독성 및 부작용에 대한 고찰", 대한한방내과학회지, 23(2), pp.222~227 (2002), 대한한방내과학회
  21. 경희대학교 약학대학, "건강기능식품의 기능성평가 체계 구축에 대한 연구" (2002), 식품의약품안전청
  22. Leung, H.W, "Antioxidant enzymes activity involvement in luteolin - induced human lung squamous carcinoma CH27 cell apoptosis", Eur. J. Pharmacol., 534, pp.12~18 (2006)
  23. Leung, H.W, "Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis", Eur. J. Pharmacol., 508, pp.77~83 (2005)
  24. Park, E, "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., 33, pp.415~424 (2005)
  25. Yip, E.C, "Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c - Jun N - terminal kinase - dependent mechanism", Cell Biol. Toxicol., 22, pp.293~302 (2006)
  26. Ko, H.C, "The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus - infected human epithelial cells", J. Ethnopharmacol, 107, pp.205~210 (2006)
  27. 박선관, "사염화탄소 유발 간독성에 대한 금은화의 작용", 응용약물학회지, 10(4), pp.32~36 (2002), 한국응용약물학회
  28. 김상찬, "금은화 화장수가 DNCB로 유발된 접촉성피부염에 미치는 영향", 대한본초학회지, 21(1), pp.9~15 (2006), 대한본초학회
  29. 이정노, "수용성 금은화 추출물이 Trimellitic Anhydride 유도 마우스 접촉성 과민반응에 미치는 영향", 대한본초학회지, 23(2), pp.51~58 (2008), 대한본초학회
  30. 배지현, "식중독 유발세균의 증식에 미치는 금은화 추출물의 항균효과", 한국식품과학회지, 37(4), pp.642~647 (2005), 한국식품과학회
  31. Lee, J.H, "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., 7, pp.79~83 (2001)
  32. Tae, J, "Anti - inflammatory effect of Lonicera japonica in proteinase - activated receptor 2 - mediated paw edema", Clin. Chim. Acta.., 330, pp.165~171 (2003)
  33. Kim, J.A, "Inhibitory effect of luteolin on TNF - alpha - induced IL-8 production in human colon epithelial cells", Int. Immunopharmacol, 5, pp.209~217 (2005)
  34. Suh, S.J, "The naturally occurring biflavonoid, ochnaflavone, inhibits LPS - induced iNOS expression, which is mediated by ERK1", 2 via NF - kappaB regulation, in RAW264.7 cells, 2006, pp.447, 136~146
  35. 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, 28, pp.562~ (1990)
  36. 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, 19, pp.27~34 (1992)
  37. 김동현, "한방약리학", pp.133~135 (2006), 신일상사
  38. Chang, W.C, "Inhibition of platelet activation and endothelial cell injury by polyphenolic compounds isolated from Lonicera japonica Thunb", Prostaglandins Leukot Essent Fatty Acids, 45, pp.307~312 (1992)
  39. Chun-Whan Choi, "Antioxidant Constituents and a New Triterpenoid Glycoside from Flos Lonicerae", Archives of Pharmacal Research, 30(1), pp.1~7 (2007), 대한약학회
  40. Tang, D, "Rapid and simple method for screening of natural antioxidants from Chinese herb Flos Lonicerae Japonicae by DPPH-HPLC-DAD- TOF", MS, 2008, pp.31, 3519~3526
  41. Wang, T, "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.., 1180, pp.53~58 (2008)
  42. Plata, E.J, "Growth and haematologic properties of the BALB", wm strain of inbred mice, 1972, pp.22, 712~720
  43. Yamaguchi, C, "Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice", Exp. Anim, 32, pp.1~11 (1983)
  44. Hyeung-Sik Lee, "Single Oral Dose Toxicity Study of Water Extractsof Picrorrhiza Rhizoma In ICR Mice", 한국독성학회지, 22(2), pp.117~126 (2006), 한국독성학회
  45. JaeHyun Lee, "Single Subcutaneous Dose Toxicity of Polycan?, a β-Glucan Originated from Aureobasidium in Mice", Laboratory Animal Research, 21(4), pp.299~305 (2005), 한국실험동물학회
  46. Banks, W.J, "Female reproductive system. In: Applied veterinary histology", pp.506~526 (1986), Williams & Wilkins
  47. Pineda, M.H, "Female reproductive system. In: endocrinology and reproduction", pp.303~354 (1989), Lea & Febiger
  48. U.S. Environmental Protection Agency, "Health Effects Test Guidelines OPPTS 870.10 0, Acute Toxicity Testing Background", ~ (1998)

관련 논문AI추천

이 간행물의 다른 논문 (24건)