黄连生物碱降糖作用研究及构效关系初探  

Preliminary evaluation of antihyperglycemic effect of Rhizoma Coptidis alkaloids and their structure-activity relationships

作　　者：马航[1] 胡慭然[1] 邹宗尧 王德珍[1] 叶小利[2] 李学刚[1,3,4] 

机构地区：[1]西南大学药学院,重庆400716 [2]西南大学生命科学学院,重庆400716 [3]西南大学重庆市药效评价工程技术研究中心,重庆400716 [4]西南大学重庆市药物过程与质量控制工程技术研究中心,重庆400716

出　　处：《中国药理学通报》2015年第11期1575-1579,共5页Chinese Pharmacological Bulletin

基　　金：科技部十二五科技支撑计划项目(No 2011BAI13B02-1);2013年重庆市“百名工程技术高端人才培养计划”;教育部博士点基金(No 20130182110023);西南大学校地合作基金(No Sz201312;Sz201401)

摘　　要：目的研究黄连治疗糖尿病的物质基础。方法考察了黄连生物碱(小檗碱、黄连碱、巴马汀、表小檗碱和药根碱)对自发性糖尿病小鼠KK-Ay的降糖活性。结果连续给予生物碱(225 mg·kg^(-1)·d^(-1),灌胃)40d后,小檗碱和黄连碱能明显降低小鼠空腹血糖值并改善糖耐量;表小檗碱控制体重增长作用最强;小檗碱减缓了胰岛素(INS)抵抗;药根碱明显提高肝脏超氧化物歧化酶(SOD)含量,降低丙二醛(MDA)水平。结论黄连生物碱中起降糖作用的主要是小檗碱和黄连碱,巴马汀、表小檗碱和药根碱在治疗糖尿病方面发挥不同的协同作用。推测生物碱母核中A环C2、C3位的亚甲二氧基和D环C9、C10位的甲氧基同时存在时,降糖作用最强。Aim To find the material foundation of treatment for diabetes in Coptidis Rhizoma ( RC ) . Methods The antihyperglycemic effect of RC alka-loids ( berberine, coptisine, palmatine, epiberberine, and jatrorrhizine) was evaluated in spontaneity diabe-tes KK-Ay mice. Results After 40 days′ oral admin-istration ( 225 mg · kg-1 · d-1 , ig ) , berberine and coptisine significantly suppressed the elevated fasting blood glucose level and ameliorated the glucose toler-ance . Body weight gain of KK-Ay mice was significant-ly decreased in the epiberberine-treated group. Berber-ine improved insulin resistance and jatrorrhizine in-creased the SOD activity, decreased the MDA level. Conclusions These results indicate that the main an-tihypoglycemic effect constituents are berberine and coptisine, while they show different mechanisms. Pal-matine, epiberberine and jatrorrhizine display different potential roles in the treatment of diabetes. The meth-ylene-dioxy groups at the C-2 , C-3 , C-9 and C-10 po-sitions are indispensable for antihyperglycemic effect of RC alkaloids.

关 键 词：黄连生物碱 糖尿病 KK-AY小鼠 氧化应激 糖耐量 胰岛素 

分 类 号：R-332[医药卫生] R284.1