甘草地上部分的安全性评价
|
摘要
目的:评价甘草地上部分的毒理学安全性,为合理利用甘草地上部分资源提供依据。方法:采用急性经口毒性实验、小鼠骨髓细胞微核实验、小鼠精子畸形实验以及基于炎症模型的安全性实验的方法,并对实验结果进行统计分析与判定。结果:甘草地上部分水提物和醇提物对小鼠的最大耐受剂量(MTD)分别为96,128 g·kg~(-1),醇提物大孔树脂富集产物对小鼠有伤害且表现出性别差异。骨髓细胞微核实验甘草地上部分水提物低、中、高剂量(8,16,32 g·kg~(-1))组和正常组的微核率分别为0. 28%,0. 34%,0. 26%,0. 22%(雌性)和0. 32%,0. 30%,0. 36%,0. 28%(雄性);小鼠精子畸形实验甘草地上部分低、中、高剂量(8,16,32 g·kg~(-1))组和正常组的精子畸形率分别为3. 16%,3. 01%,2. 67%,3. 23%;微核率和精子畸形率与正常组比较无明显增加; 30 d重复灌胃水提物和醇提物对模型大鼠的一般情况无影响,其中,与正常组比较,甘草地上部分醇提组心脏质量显著降低(P <0. 05),肝脏质量、肝脏指数和肾脏指数明显升高(P <0. 05);水提组与醇提组的球蛋白与血肌酐明显升高(P <0. 05),个别大鼠氨基转移酶异常;解剖学考察发现4例肉眼可见的肝病变,其中甘草地上部分水提组3例,甘草地上部分醇提组1例,组织病理学检查发现肝细胞变性与组织炎症,与出现生化指标与脏器指数异常的大鼠一致。结论:甘草地上部分水提物、醇提物具有潜在毒性,水提物未显示对小鼠有遗传毒性,其安全性尚需进一步研究。
Objective: To evaluate the toxicological safety of over-ground parts of Glycyrrhiza uralensis,in order to provide basis for the rational utilization of over-ground parts of Glycyrrhizae Radix et Rhizoma recourses.Method: Mice acute oral toxicity test,micronucleus test of mice bone marrow,mice sperm shape abnormality test and toxicological test based on chronic nonbacterial prostatitis model were carried out. Result: Maximal tolerable dose( MTD) of over-ground parts of G. uralensis water extract( WE) and alcohol extract( AE) were 96,128 g·kg~(-1),respectively. Macro-porous resin enriched product of AE was harmful to mice, with gender differences. Micronucleus rates of each dose( 8,16,32 g · kg~(-1)) group and control group for female mouse were 0. 28%,0. 34%,0. 26% and 0. 22%,respectively. Micronucleus rates of each dose( 8,16,32 g·kg~(-1))group and control group for male mouse were 0. 32%,0. 30%,0. 36% and 0. 28%,respectively. Sperm shape abnormality rates of each dose group and control group were 3. 16%,3. 01%,2. 67% and 3. 23%,respectively.Micronucleus rate and sperm shape abnormality rate had no significant increase compared with the negative control.The 30-day repeated intragastric WE and AE had no effect on the general conditions of the model rats. Compared with normal group,AE group showed a significant decrease in heart weight,and significant increases in liver weight,liver index and kidney index( P < 0. 05). Both of AE and WE group showed significant increases in globulin( GLB) and creatinine( CRE) levels( P < 0. 05). The transaminases of individual rats were abnormal.Four liver pathological changes were found in necropsy,histopathological examination revealed that liver cells degeneration,necrosis and liver tissue inflammation occurred in the individual rats with abnormalities in biochemical index and organ index. Conclusion: The results indicated that both of WE and AE have potential toxicity. WE does not show any genetic toxicity to mice. Therefore,further studies shall be made for toxicological safety of over-ground parts of G. uralensis.
Objective: To evaluate the toxicological safety of over-ground parts of Glycyrrhiza uralensis,in order to provide basis for the rational utilization of over-ground parts of Glycyrrhizae Radix et Rhizoma recourses.Method: Mice acute oral toxicity test,micronucleus test of mice bone marrow,mice sperm shape abnormality test and toxicological test based on chronic nonbacterial prostatitis model were carried out. Result: Maximal tolerable dose( MTD) of over-ground parts of G. uralensis water extract( WE) and alcohol extract( AE) were 96,128 g·kg~(-1),respectively. Macro-porous resin enriched product of AE was harmful to mice, with gender differences. Micronucleus rates of each dose( 8,16,32 g · kg~(-1)) group and control group for female mouse were 0. 28%,0. 34%,0. 26% and 0. 22%,respectively. Micronucleus rates of each dose( 8,16,32 g·kg~(-1))group and control group for male mouse were 0. 32%,0. 30%,0. 36% and 0. 28%,respectively. Sperm shape abnormality rates of each dose group and control group were 3. 16%,3. 01%,2. 67% and 3. 23%,respectively.Micronucleus rate and sperm shape abnormality rate had no significant increase compared with the negative control.The 30-day repeated intragastric WE and AE had no effect on the general conditions of the model rats. Compared with normal group,AE group showed a significant decrease in heart weight,and significant increases in liver weight,liver index and kidney index( P < 0. 05). Both of AE and WE group showed significant increases in globulin( GLB) and creatinine( CRE) levels( P < 0. 05). The transaminases of individual rats were abnormal.Four liver pathological changes were found in necropsy,histopathological examination revealed that liver cells degeneration,necrosis and liver tissue inflammation occurred in the individual rats with abnormalities in biochemical index and organ index. Conclusion: The results indicated that both of WE and AE have potential toxicity. WE does not show any genetic toxicity to mice. Therefore,further studies shall be made for toxicological safety of over-ground parts of G. uralensis.
引文
[1] Isbrucker R A, Burdock G A. 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[J]. Regul Toxicol Pharm,2006,46(3):167-192.
[2]雍晓静,刘钢.宁夏乌拉尔甘草地上资源的开发利用[J].资源开发与市场,2004,20(5):381-382.
[3]郭忠军,麻常娟.甘草地上部分黄酮研究概况[J].航空航天医药,2005,16(1):62-64.
[4]张学静.甘草茎叶及根中黄酮和多糖类成分积累动态研究[D].北京:北京中医药大学,2009.
[5]康雪芳,李红丽,王文全,等.甘草地上部分脂溶性总黄酮抗氧化活性研究[J].环球中医药,2016,9(5):567-570.
[6]郑巧云.甘草叶提取物抗慢性非细菌性前列腺炎作用的研究[D].北京:北京中医药大学,2011.
[7]李红丽,康雪芳,吴宏辉,等.甘草地上部分水提液总黄酮纯化工艺研究[J].湖北中医药大学学报,2017,19(5):39-42.
[8]张鲁,张媛,王文全,等.甘草地上部分总黄酮提取工艺优化及抗氧化活性研究[J].辽宁中医药大学学报,2018,20(4):55-59.
[9] XIE J H, CHEN Y L, WU Q H, et al. Gastro protective and anti-Helicobacter pylori potential of herbal formula HZJW:safety and efficacy assessment[J].BMC Complem Altern M,2013,13(1):119-119.
[10] GB15193. 5-2014食品安全国家标准[S]. 2014:2-4.
[11]贾世山,马超美,王建民.甘草叶中黄酮类成分的化学研究[J].药学学报,1990(10):758-762.
[12]党延启,段菊,倪荣镇,等.异戊烯基黄酮的生物活性及构效关系[J].中国实验方剂学杂志,2015,21(17):213-218.
[13] SUN F,Indran I R,ZHANG Z W,et al. A novel prostate cancer therapeutic strategy using icaritinactivated arylhydrocarbon-receptor to co-target androgen receptor,and its splice variants[J]. Carcinog,2015,36(7):757-768.
[14] Wtjen W,Weber N,LOU Y J,et al. Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6 glioma cells[J]. Food Chem Toxicol,2007,45(1):119-124.
[15]国家卫计委关于印发《新食品原料申报与受理规定》和《新食品原料安全性审查规程》的通知[J].中国食品卫生杂志,2014,26(1):13.
[16]朱周靓,严峻,郑云燕,等.杜仲叶安全性的毒理学评价[J].浙江预防医学,2017,29(5):443-448.
[17]廖萍.白木香叶提取物毒理学安全性评价的实验研究[D].长沙:中南大学,2014.
[18]黄郑隽,阙慧卿,彭华毅,等.雷公藤内酯醇对雄性大鼠的生殖毒性及其机制研究[J].中国中药杂志,2015,40(23):4655-4659.
[19]王伽伯,崔鹤蓉,柏兆方,等.精准医学下的中药安全性评价策略和方法:病证毒理学[J].药学学报,2016,51(11):1681-1688.
[20] Kang H K,Choi Y H,Kwon H,et al. Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its major components:in vitro and in vivo studies[J]. Food Chem Toxicol,2012,50(8):2751-2759.
[2]雍晓静,刘钢.宁夏乌拉尔甘草地上资源的开发利用[J].资源开发与市场,2004,20(5):381-382.
[3]郭忠军,麻常娟.甘草地上部分黄酮研究概况[J].航空航天医药,2005,16(1):62-64.
[4]张学静.甘草茎叶及根中黄酮和多糖类成分积累动态研究[D].北京:北京中医药大学,2009.
[5]康雪芳,李红丽,王文全,等.甘草地上部分脂溶性总黄酮抗氧化活性研究[J].环球中医药,2016,9(5):567-570.
[6]郑巧云.甘草叶提取物抗慢性非细菌性前列腺炎作用的研究[D].北京:北京中医药大学,2011.
[7]李红丽,康雪芳,吴宏辉,等.甘草地上部分水提液总黄酮纯化工艺研究[J].湖北中医药大学学报,2017,19(5):39-42.
[8]张鲁,张媛,王文全,等.甘草地上部分总黄酮提取工艺优化及抗氧化活性研究[J].辽宁中医药大学学报,2018,20(4):55-59.
[9] XIE J H, CHEN Y L, WU Q H, et al. Gastro protective and anti-Helicobacter pylori potential of herbal formula HZJW:safety and efficacy assessment[J].BMC Complem Altern M,2013,13(1):119-119.
[10] GB15193. 5-2014食品安全国家标准[S]. 2014:2-4.
[11]贾世山,马超美,王建民.甘草叶中黄酮类成分的化学研究[J].药学学报,1990(10):758-762.
[12]党延启,段菊,倪荣镇,等.异戊烯基黄酮的生物活性及构效关系[J].中国实验方剂学杂志,2015,21(17):213-218.
[13] SUN F,Indran I R,ZHANG Z W,et al. A novel prostate cancer therapeutic strategy using icaritinactivated arylhydrocarbon-receptor to co-target androgen receptor,and its splice variants[J]. Carcinog,2015,36(7):757-768.
[14] Wtjen W,Weber N,LOU Y J,et al. Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6 glioma cells[J]. Food Chem Toxicol,2007,45(1):119-124.
[15]国家卫计委关于印发《新食品原料申报与受理规定》和《新食品原料安全性审查规程》的通知[J].中国食品卫生杂志,2014,26(1):13.
[16]朱周靓,严峻,郑云燕,等.杜仲叶安全性的毒理学评价[J].浙江预防医学,2017,29(5):443-448.
[17]廖萍.白木香叶提取物毒理学安全性评价的实验研究[D].长沙:中南大学,2014.
[18]黄郑隽,阙慧卿,彭华毅,等.雷公藤内酯醇对雄性大鼠的生殖毒性及其机制研究[J].中国中药杂志,2015,40(23):4655-4659.
[19]王伽伯,崔鹤蓉,柏兆方,等.精准医学下的中药安全性评价策略和方法:病证毒理学[J].药学学报,2016,51(11):1681-1688.
[20] Kang H K,Choi Y H,Kwon H,et al. Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its major components:in vitro and in vivo studies[J]. Food Chem Toxicol,2012,50(8):2751-2759.