狼毒(月腺大戟)毒性部位诃子汤制前后肠道毒性变化与成分组成变化的相关性研究  

Correlation between intestinal toxicity and composition changes of toxic parts from Euphorbia ebracteolata before and after Terminalia chebula soup processing

作　　者：林伟豪 郁红礼[1,2,3] 吴皓[1,2,3] 王欣之[1] 崔小兵[1] 刘睿[1] 刘璐 曹杰 曾敏 许艳青 LIN Wei-hao;YU Hong-li;WU Hao;WANG Xin-zhi;CUI Xiao-bing;LIU Rui;LIU Lu;CAO Jie;ZENG Min;XU Yan-qing(Pharmacology College,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory of Chinese Medicine Processing,Nanjing 210023,China;Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院 [2]江苏省中药炮制重点实验室 [3]国家教育部中药炮制规范化及标准化工程研究中心

出　　处：《中国中药杂志》2024年第9期2441-2450,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金重点项目(82130116);国家自然科学基金面上项目(82374143)。

摘　　要：为探究狼毒(月腺大戟)诃子汤制前后肠道毒性变化与成分组成变化的相关性,在整体动物模型水平灌胃给药,以小鼠的粪便含水量,肠道不同部位炎症因子及病理损伤情况为指标,比较月腺大戟生品二氯甲烷提取部位(二氯部位)、诃子汤制品二氯部位与模拟诃子汤制月腺大戟二氯部位的肠道毒性作用差异,考察诃子汤制对月腺大戟肠道毒性的影响。同时构建月腺大戟和诃子成分结构数据库,采用HPLC-TOF-MS分析这3个提取部位的二萜类成分与鞣质酚酸类成分组成变化。采用HPLC测定炮制前后月腺大戟饮片和炮制后锅壁残留物中的4种主要二萜类成分ent-11α-hydroxyabicta-8(14)、13(15)-dien-16,12-olide(HAO)、jolkinolide B(JNB)、fischeria A(FA)、jolkinolide E(JNE)的含量,考察诃子汤炮制是否对二萜类成分的含量与结构产生影响。结果表明,月腺大戟生品二氯部位组可显著增加小鼠的粪便含水量和各肠段炎症因子TNF-α和IL-1β释放水平,且发现肠道组织受损并伴随明显炎症细胞浸润,而与生品二氯部位组比较,模拟诃子汤制月腺大戟二氯部位组肠道组织损伤减轻,炎症细胞浸润减少,肠道毒性显著下降。质谱分析结果显示月腺大戟二氯部位模拟诃子汤制后二萜类成分含量无明显差异,但新增了大量来源于诃子的鞣质酚酸类等成分。HPLC结果显示,月腺大戟诃子汤炮制后4种萜类成分含量有不同程度下降,下降幅度在-0.35%~-19.74%,下降部分主要残留于锅壁,表明诃子汤制并未改变月腺大戟中毒性二萜类成分的结构。诃子汤中鞣质酚酸类成分拮抗作用是月腺大戟诃子汤炮制后肠道毒性下降的主要原因,民族药诃子汤炮制狼毒具有科学性。This study aims to explore the correlation between intestinal toxicity and composition changes of Euphorbia ebracteolata before and after Terminalia chebula soup(TCS) processing. Intragastric administration was performed on the whole animal model. By using fecal water content, inflammatory causes, and pathological damage of different parts of the intestinal tract of mice as indexes, the differences in intestinal toxicity of dichloromethane extraction of raw E. ebracteolata(REDE), dichloromethane extraction of TCS, and dichloromethane extraction of E. ebracteolata after simulated TCS processing(STREDE) were compared, so as to investigate the effect of TCS processing on the intestinal toxicity of E. ebracteolata. At the same time, the component databases of E. ebracteolata and T. chebula were constructed, and the composition changes of diterpenoids, tannins, and phenolic acids in the three extracted parts were analyzed by HPLC-TOF-MS. HPLC was used to compare the content of four diterpenoids including ent-11α-hydroxyabicta-8(14), 13(15)-dien-16, 12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and jolkinolide E(JNE) in the E. ebracteolata before and after processing and the residue of container wall after processing, so as to investigate the effect of TCS processing on the content and structure of the diterpenoids. The results showed that the REDE group could significantly increase the fecal water content and the release levels of TNF-α and IL-1β from each intestinal segment, and intestinal tissue damage was accompanied by significant infiltration of inflammatory cells. However, compared with the REDE group, the intestinal tissue damage in the STREDE group was alleviated, and the infiltration of inflammatory cells decreased. The intestinal toxicity significantly decreased. Mass spectrometry analysis showed that there was no significant difference in the content of diterpenoids of REDE before and after simulated TCS processing, but a large number of tannins and phenolic acids were added. The results of HPLC sh

关 键 词：月腺大戟 诃子汤制 模拟炮制 肠道毒性 二萜类成分 成分变化 

分 类 号：R284.1[医药卫生—中药学]