盐益智仁-盐小茴香药对止泻活性部位筛选及“谱效”关系研究  

Screening of active antidiarrheal components and study of the“spectrum⁃effect”relationship of salt⁃processed Alpiniae oxyphyllae Fructus⁃Foeniculi Fructus medicines

作　　者：李红伟[1,2,3] 徐若颖 周宁 曹彦刚[1] 田连起 石延榜[1] 李凯[1,2,3] LI Hongwei;XU Ruoying;ZHOU Ning;CAO Yangang;TIAN Lianqi;SHI Yanbang;LI Kai(Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao,Henan Province,Zhengzhou 450046;Henan Research Center for Special Processing Technology of Chinese Medicine,Zhengzhou 450046)

机构地区：[1]河南中医药大学,郑州450046 [2]豫药全产业链研发河南省协同创新中心,郑州450046 [3]河南省中药特色炮制技术工程研究中心,郑州450046

出　　处：《中国比较医学杂志》2024年第7期48-59,共12页Chinese Journal of Comparative Medicine

基　　金：河南省科技攻关(232102311214,242102310542);河南省科技研发计划联合基金(优势学科培育类)项目(232301420073)。

摘　　要：目的筛选盐益智仁-盐小茴香药对(YZYH)止泻活性部位,并通过“谱效”关系研究推测其药效物质基础和质量标志物。方法制备大鼠脾肾阳虚泄泻模型,测定盐益智仁-盐小茴香药对石油醚(YZYH⁃L)、乙酸乙酯(YZYH⁃M)、水(YZYH⁃H)3部位药效指标,包括体重、肛温、腹泻潜伏期(diarrhea incubation period,DIP)、腹泻指数(diarrheal index,DI)等行为学指标及一氧化氮合成酶(nitric oxide synthetase,NOS)、环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)、磷酸肌酸激酶(creatine phosphate kinase,CPK)等生化指标;建立不同部位高效液相色谱(high performance liquid chromatography,HPLC)图谱,采用灰色关联法分析各部位化学成分与止泻药效指标间的“谱效”关系。结果与空白对照组大鼠相比,15 d后,模型组大鼠出现泄泻证主症关键病理指标—水样便,同时,伴随食后腹胀、食欲不振和弓背等脾阳和肾阳虚泄泻的次症典型特征;给与治疗药物后,泄泻主症和次症均有不同程度的改善,其中阳性药、YZYH⁃M部位第28天后泄泻模型大鼠关键指标DIP极显著延长(P<0.01)、DI极显著降低(P<0.01),以及脾、肾阳虚泄泻的次症典型特征代表性指标体重、24 h摄食、饮水量、肛温和血清生化指标NOS、cGMP、CPK等活性的调节作用均较其它给药组好;“谱效”关系研究表明茴香醛、4号色谱峰等成分与DIP、DI、NOS、cGMP、CPK 5个药效指标的关联度重要。结论YZYH⁃M部位为药对止泻活性部位,其作用机制与抑制胃肠功能亢进和调节机体能量代谢与免疫相关;茴香醛及4号峰作为药对的质量标志物。Objective To screen the active antidiarrheal components of salt⁃processed Alpiniae oxyphyllae Fructus⁃Foeniculi Fructus medicines(YZYH)and investigate its pharmacological basis and quality markers by examining its“spectrum⁃effect”relationship.Methods A spleen and kidney yang deficiency model of diarrhea was established in rats.The pharmacodynamic indexes of YZYH in petroleum ether,ethyl acetate,and water fractions were measured,including behavioral indicators such as body weight,anal temperature,diarrhea incubation period(DIP),diarrhea index(DI),and biochemical indicators such as nitric oxide synthase(NOS),cGMP,and creatinine phosphokinase(CPK).We analyzed the components of YZYH by high performance liquid chromatography,and analyzed the“spectrum⁃effect”relationship between the chemical components and the antidiarrheal efficacy indicators using the grey correlation method.Results Compared with the blank control group,rats in the model group developed watery stools after 15 days,which was the key pathological index of the main syndrome of diarrhea.Rats in the model group also developed abdominal distension,loss of appetite,and back arching,as secondary symptoms of spleen and kidney yang deficiency diarrhea.Administration of the therapeutic drugs improved both the main and secondary symptoms of diarrhea.The positive drug and YZYH⁃M significantly prolonged DIP(P<0.01)and decreased DI(P<0.01)after 28 days.These key indexes of diarrhea,as well as body mass,24 h food intake,water intake,anal temperature,and the serum biochemical indexes NOS,cGMP,CPK were all improved in the positive drug and YZYH⁃M groups.Examination of the spectral effect relationship showed that anisaldehyde,chromatographic peak 4,and other components were correlated with the pharmacodynamic indexes of DIP,DI,NOS,cGMP,and CPK.Conclusions The ethyl acetate fraction was the active antidiarrheal fraction of salt⁃processed Alpiniae oxyphyllae Fructus⁃Foeniculi Fructus medicines.It acts by inhibiting gastrointestinal hyperfunction,r

关 键 词：盐益智仁-盐小茴香药对 止泻作用 活性部位 “谱效”关系 灰色关联法 茴香醛 

分 类 号：R-33[医药卫生]