摘要
针对仙灵骨葆口服制剂致肝损伤风险问题,比较2种不同提取工艺致大鼠肝损伤情况差异,并从有关成分含量差别角度探明肝毒性与工艺相关性。将30只SD雄性大鼠随机分为正常组、片剂工艺提取物不同剂量组、胶囊工艺提取物不同剂量组,每组6只,各给药组连续灌胃给药4周;通过考察大鼠体质量、肝功能血生化指标、肝脏系数、肝脏病理变化,综合评价不同提取物造成的肝损伤情况;建立同时测定提取物中淫羊藿苷、宝藿苷Ⅰ与补骨脂酚含量的高效液相检测方法,比较2种工艺下3种成分的含量差别。结果显示2种提取物均引起大鼠肝损伤,与正常组相比,片剂工艺提取物在研究剂量下,造成体质量增长缓慢,甘油三酯水平显著升高(P<0.05),脏脑比显著降低(P<0.05),肝组织出现脂肪变性;胶囊工艺提取物在研究剂量下,造成体质量增长缓慢,丙氨酸氨基转移酶水平显著升高(P<0.05),体质量、肝脏质量、脏脑比显著降低(P<0.05),肝组织出现脂肪变性和炎性细胞浸润;2种工艺提取物相比,胶囊工艺提取物组引发肝损伤风险较高;在完成液相检测方法学内容的基础上,经检测胶囊工艺提取物中淫羊藿苷和宝藿苷Ⅰ含量分别为片剂工艺提取物中的0.83、0.81倍,补骨脂酚含量为片剂工艺提取物中的29.80倍,说明胶囊工艺提取物较高的肝损伤风险可能由补骨脂酚含量更高所引起。综上,2种提取物造成大鼠肝损伤差异与提取工艺密切相关,在制剂生产与临床应用中应予以重视。
In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation,this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components.Thirty male Sprague-Dawley(SD)rats were randomly divided into a normal group,tablet extract groups of different doses,and capsule extract groups of different doses,with 6 rats in each group.Each group received continuous oral administration for 4 weeks.The assessment of liver injury caused by different extracts was conducted by examining rat body weight,liver function blood biochemical indicators,liver coefficient,and liver pathological changes.In addition,a high-performance liquid chromatography(HPLC)method was established to simultaneously determine the content of icariin,baohuoside I,and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes.The results showed that both extracts caused liver injury in rats.Compared with the normal group,the tablet extract groups,at the studied dose,led to slow growth in body weight,a significant increase in triglyceride levels(P<0.05),a significant decrease in liver-to-brain ratio(P<0.05),and the appearance of hepatic steatosis.The capsule extract groups,at the studied dose,resulted in slow growth in body weight,a significant increase in aspartate aminotransferase levels(P<0.05),a significant decrease in body weight,liver weight,and liver-to-brain ratio(P<0.05),and the presence of hepatic steatosis and inflammatory cell infiltration.In comparison,the capsule extraction process had a higher risk of liver injury.Furthermore,based on the completion of the liquid chromatography method,the content of icariin and baohuosideⅠin the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups,respectively,while the bakuchiol c
作者
彭俙仪
张林
于书伟
翟裕祺
郭兆娟
PENG Xi-yi;ZHANG Lin;YU Shu-wei;ZHAI Yu-qi;GUO Zhao-juan(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Institute of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;School of Chinese Materia Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国中药杂志》
CSCD
北大核心
2023年第24期6645-6652,共8页
China Journal of Chinese Materia Medica
基金
北京中医药大学基本科研业务费“揭榜挂帅”项目(2022-JYB-JBZR-020)
北京市自然科学基金面上项目(7222277)
国家自然科学基金青年基金项目(82004053)。
