藏药塞北紫堇总生物碱降尿酸活性及其化学成分研究  

Uric Acid-lowering Activity and Chemical Constituents of Total Alkaloids from Corydalis impatiens

作　　者：邱咏薇 闵彤彤 周鹏 张亚梅 杨书洁 钟国跃 QIU Yongwei;MIN Tongtong;ZHOU Peng;ZHANG Yamei;YANG Shujie;ZHONG Guoyue(Research Center of Chinese Medicine Resource and National Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;State Key Laboratory of Innovative Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment,Jiangxi University of Chinese Medicine,Nanchang 330004,China;National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine,Nanchang 330000,China)

机构地区：[1]江西中医药大学中药资源与民族药研究中心,南昌330004 [2]江西中医药大学经典名方现代中药创制全国重点实验室,南昌330004 [3]中药固体制剂制造技术国家工程中心,南昌330000

出　　处：《世界中医药》2024年第24期3748-3753,3760,共7页World Chinese Medicine

基　　金：国家重点研发计划项目(2019YFC1712300)——藏、蒙、维等民族药资源信息化共享平台构建、品种整理及繁育保护技术研究;江西省教育厅科学技术研究项目(GJJ211229)——基于JNK/p38信号通路探讨藏药玉冬赛果抗心肌缺血活性成分及作用机制。

摘　　要：目的:探讨藏药塞北紫堇总生物碱的降尿酸活性及可能的作用机制,并对其化学成分进行分离鉴定。方法:将塞北紫堇总生物碱灌胃由氧嗪酸钾盐诱导的高尿酸血症模型小鼠7 d,用试剂盒测定血清尿酸(UA)、尿素氮(BUN)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)水平,肝脏黄嘌呤氧化酶(XOD)和腺苷脱氨酶(ADA)活力。结果:与模型组比较,塞北紫堇总生物碱高、低剂量均能够显著降低急性高尿酸血症模型小鼠的血清UA、BUN和TNF-α含量(均P<0.01),显著抑制肝脏XOD和ADA活力(P<0.01,P<0.05),且呈现剂量依赖性;进一步从塞北紫堇总生物碱中分离得到11个异喹啉类生物碱成分,即吡咕咕灵(1)、四氢黄连碱(2)、碎叶紫堇碱(3)、卡维丁(4)、北美黄连碱(5)、去氢碎叶紫堇碱(6)、氧化北美黄连次碱(7)、白屈菜碱(8)、紫堇明碱(9)、紫堇块茎碱(10)、原阿片碱(11)。结论:塞北紫堇总生物碱具有显著降尿酸和肾脏保护作用,异喹啉类生物碱是其主要活性成分,且其可能的作用机制包括抑制XOD和ADA活力,以及下调炎症介质TNF-α表达等;此外,化合物6、8为首次从塞北紫堇中分离得到。Objective:To investigate the uric acid-lowering activity and possible mechanisms of action of the total alkaloids from Corydalis impatiens,and to isolate and identify its chemical components.Methods:The total alkaloids from C.impatiens were administered by gavage to mice with hyperuricemia induced by potassium oxonate for 7 days.Serum uric acid(UA),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)levels were measured using assay kits.The activities of hepatic xanthine oxidase(XOD)and adenosine deaminase(ADA)were also assessed.Results:Compared with the model group,both high and low doses of the total alkaloids of C.impatiens significantly reduced serum UA,BUN,and TNF-αlevels(all P<0.01),and significantly inhibited the activities of hepatic XOD and ADA(P<0.01,P<0.05),showing a dose-dependent effect.Eleven isoquinoline alkaloids were isolated from C.impatiens total alkaloids,including bicuculline(1),tetrahydrocoptisine(2),cheilanthifoline(3),corydaine(4),β-hydrastine(5),dehydrocheilanthifoline(6),oxyhydrastinine(7),chelidonine(8),corlumine(9),corytuberine(10),and protopine(11).Conclusion:The total alkaloids from C.impatiens have significant uric acid-lowering and kidney-protective effects.Isoquinoline alkaloids are the main active components,and the potential mechanisms include inhibiting XOD and ADA activities and downregulating the expression of inflammatory mediators such as TNF-α.Additionally,compounds 6 and 8 were isolated for the first time from C.impatiens.

关 键 词：塞北紫堇 生物碱 高尿酸血症 藏药 代谢性疾病 哇夏嘎 活性成分 

分 类 号：R285.5[医药卫生—中药学]