독성대사체를 생성하는 다빈도사용 한약재의 안전성등급화 - 천궁, 당귀, 감초, 숙지황을 중심으로 -
Safety classification for frequently-used herbal medicines inducing toxic metabolites
0
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
The new formular for herbal medicine-safety classification in terms of evidence-based medicine was developed and applied to evaluate various herbal medicines in the previous study. This study is aimed to evaluate the frequently-used herbal medicines inducing toxic metabolites or reactive intermediates(RI), such as Ligusticum wallichii Franch, Angelica sinensis, Glycyrrhizae Radix, Rehmanniae Radix, based on 6 safety grades calculated from human equivalent dose(HED)-based MOS(margin of safety). HED-based MOS can be explained as the ratio of theoretical ALD(approximate lethal dose) of human as LD1(lethal dose of 1%)/ clinical maximum dose as ED99(Effective dose of 99%). The herbal medicine showing the ratio less than 1 belongs to Class 1, but the herbal medicine showing the ratio more than 500 belongs to Class 6 with the lowest toxicity. As a result, they were evaluated as class 2 for Angelica sinensis and Glycyrrhizae Radix, class 3 for Ligusticum wallichii Franch and Rehmanniae Radix. These resultant grades for 4 herbal medicines were lower than the grade expected under consideration that these herbal medicines are used very frequently in oriental clinics. These low grades would be due to their ingredients which is biotransformed to toxic metabolites.
Abstract
The new formular for herbal medicine-safety classification in terms of evidence-based medicine was developed and applied to evaluate various herbal medicines in the previous study. This study is aimed to evaluate the frequently-used herbal medicines inducing toxic metabolites or reactive intermediates(RI), such as Ligusticum wallichii Franch, Angelica sinensis, Glycyrrhizae Radix, Rehmanniae Radix, based on 6 safety grades calculated from human equivalent dose(HED)-based MOS(margin of safety). HED-based MOS can be explained as the ratio of theoretical ALD(approximate lethal dose) of human as LD1(lethal dose of 1%)/ clinical maximum dose as ED99(Effective dose of 99%). The herbal medicine showing the ratio less than 1 belongs to Class 1, but the herbal medicine showing the ratio more than 500 belongs to Class 6 with the lowest toxicity. As a result, they were evaluated as class 2 for Angelica sinensis and Glycyrrhizae Radix, class 3 for Ligusticum wallichii Franch and Rehmanniae Radix. These resultant grades for 4 herbal medicines were lower than the grade expected under consideration that these herbal medicines are used very frequently in oriental clinics. These low grades would be due to their ingredients which is biotransformed to toxic metabolites.
참고문헌 (25)
- 중화인민공화국, "의료용 독성약품관리법", ~ (1988)
- Kim, Ellie JY, "Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines", Journal of Ethnopharmacology, 146, pp.40~61 (2013)
- 용역연구개발과제 식의약품 등 통합안전관리 기반연구 중 한약재 안전사용을 위한 등급별 차등관리 방안 연구, "식약처", ~ (2012)
- 박영철, "한약의 안전성 등급화를 위한 evidence-based approach", 대한예방한의학회지, 17(3), pp.19~31 (2013), 대한예방한의학회
- 박영철, "한약의 안전성 등급화를 통한 근거중심실용의학적 연구(1) - Aristolochic acid 함유 한약재를 중심으로 -", 대한한의학회지, 35(1), pp.114~123 (2014), 대한한의학회
- 박영철, "독성학의 분자-생화학적 원리" (2010), 한국학술정보(주)
- 이선동, "한약독성학 I" (2012), 한국학술정보(주)
- 이선동, "한약독성학 II" (2013), 한국학술정보(주)
- Yan CC, "Effects of Monocrotaline, a Pyrrolizidine Alkaloid, on glutathione Metabolism in the Rat", Huxtable Biochemical Pharmacology, 51, pp.375~379 (1996)
- Jeffrey, AM, "Risk assessment of DNA-reactive carcinogens in food", Toxicology and Applied Pharmacology, 207, pp.S628~S635 (2005)
- Zhou S, "Interactions of Herbs with Cytochrome P450", Drug metabolism review, 35(1), pp.35~98 (2003)
- Dong-Hyun Kim, "Mechanism of covalent adduct formation of aucubin to proteins", Toxicology Letters, 114, pp.181~188 (2000)
- Peter J, "Approximate lethal dose versus median lethal dose in acute toxicity testing of pharmaceuticals. A retrospective study", Arch Toxicol, 63(4), pp.343~344 (1989)
- Reagan-Shaw S, "Dose translation from animal to human studies revisited", Journal of the Federation of American Societies for Experimental Biology, 22, pp.659~661 (2008)
- Beasley V, "Introduction to Toxicology", International Veterinary Information Service, ~ (1999)
- Dietz BM, "Biological reactive intermediates(BRIs) formed from botanicaldietary supplements", Chemico-Biological Interactions, 192, pp.72~80 (2011)
- US FDA, "Safrole. 1989. PART 189—SUBSTANCES PROHIBITED FROM USE IN HUMAN FOOD, § 189.180", ~ (1989)
- Johnson BM, "In vitro formation of quinoid metabolites of the dietary supplement Cimicifuga racemosa (black cohosh)", Chem. Res. Toxicol, 16(7), pp.838~884 (2003)
- US FDA, "FDA Poisonous Plant Database-Toxicity of medicinal herbal preparations", ~ (2008)
- Editorial Committee of Chinese Materia Medica, "State Drug Administration of China. Chinese Materia Medica" (1998), Science and Technology Press;
- Isbrucker RA, "Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin", Regulatory Toxicology and Pharmacology, 46, pp.167~192 (2006)
- Materia Medica Group, "Medical Vacational College of Northern Henan", Pharmacy Bulletin, 17(2), pp.114~ (1982)