白芷的古今药用概况及香豆素类成分研究

【作者】 王梦月；

【导师】 贾敏如；

【作者基本信息】 成都中医药大学 ， 生药学， 2003， 博士

【摘要】 白芷，为伞形科植物白芷Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f.或杭白芷A. dahurica (Fisch. ex Hoffm.) Benth. et Book. f. var. formosana (Boiss.) Shan et Yuan的干燥根，为一常用中药，用于风寒感冒、鼻渊头痛、风湿痹痛等病，在临床上广泛应用。本课题对白芷的产地变迁、四大商品的栽培历史、品种变化、功能主治变化、采收加工、炮制方法的变化、药材的质量评价及入药部位进行了较详细的本草学考证。发现杭白芷的药用历史最悠久，主产地由历史上的杭州移至现今的磐安、东阳一带。北方的山西、南方的江浙一带为历史上白芷的道地产区，但由于历史的变迁，北方的白芷主产地已由山西一带变为现在的河北、河南，形成现在的祁白芷、禹白芷。白芷的应用，以明代及明以前最为广泛，功效有祛风除湿、行气止痛、止血、消痈散结、托毒排脓、生肌止痛等，清以后白芷的应用范围逐渐缩小，其中止血、解蛇毒等功能已不广泛使用。南北方白芷的采收时间有较大差异，我们认为历代本草记载“八月采根”及“自芷寒犹采”反映的是我国北方白芷的采收情况。 为弄清全国商品白芷的产销情况、了解不同产区白芷的栽种、采收、加工方法，作者先后深入浙江杭州、东阳、磐安，河北石家庄、保定、安国，河南郑州、禹县、长葛，四川遂宁、安岳、达州、渠县、南充等4省14市(县)的白芷产地进行了实地调查，查阅了大量相关历史资料，发现川白芷产量最大，约占全国商品白芷的70％以上，且质量上乘，畅销国内外，亩产最高；杭白芷的产量最小，约占5％；祁白芷及禹白芷产量较小，分别占10％、15％，主要供地方使用；发现目前白芷产区的加工方法不尽合理，各产区目前仍在广泛采用硫磺熏法，此法对白芷的香豆素及挥发油均有较大损失。 运用柱层析、薄层层析等方法对白芷根中的主要成分—香豆素类进行提取、分离，从自芷根中得到了10个结晶，运用UV、IR、HNMR、MS等方法鉴定了其成都中医药大学博士学位论文中的p一谷幽醇、异欧前胡素、欧前胡素、蛇床子素、东蓑若内酷、花椒毒素、白当归素、水合氧化前胡素8个成分，其中p一谷幽醇、蛇床子素为首次从白芷类药材中分得，东蓖若内醋、花椒毒素为首次从杭白芷An如licadahurica (Fiseh.ex Hof伽.)Yuan中分得。Benth.et Hook.f.var.f’Or功osana(Boiss.)Shanet 考察了不同采收时间、不同加工方法(微波干燥、远红外千燥等)、不同产地等对白芷主要香豆素类成分及总香豆素含量的影响，结果发现白芷在七月中旬根中香豆素类成分含量最高，而加工方法以晒干为高、硫熏最低。对白芷香豆素类成分在根、茎、叶、果实中的分布进行了研究，发现白芷果实中香豆素类成分的含量最高、茎中的含量最低、根的木质部中几乎不含有香豆素。对全国四大商品白芷中的香豆素的含量进行了测定，发现四大商品白芷中香豆素的含量有较大差异。对不同产地的川白芷中香豆素的含量也进行了测定，发现南充产白芷的含量最高。 从白芷中提取了总香豆素(AGC)，并首次对白芷总香豆素类成分进行了抗炎、镇痛和解痉实验，首次发现总香豆素类成分具有明显的镇痛和解痉作用，无明显的抗炎作用。首次对分得的异欧前胡素、欧前胡素、白当归素、水合氧化前胡素进行了抗炎、镇痛和解痉作用比较研究，结果发现四种香豆素类成分均无明显的抗炎活性;欧前胡素、异欧前胡素具有明显的镇痛作用，为白芷镇痛的活性成分之一;欧前胡素、异欧前胡素、水合氧化前胡素均有明显的解痉作用，能明显缓解氯化钡所致兔肠平滑肌痉挛，对乙酞胆碱所致的兔肠平滑肌痉挛无明显缓解作用;白当归素无明显解痉作用。总香豆素、欧前胡素、异欧前胡素、水合氧化前胡素对兔肠平滑肌的正常舒缩均无影响。更多还原

【Abstract】 Baizhi, which was recorded in shennongbencaojing firstly, is frequently used for treating pain . Herbalogical study on history, variety, function and suitable diseases .collecting time,processing method , quality assessment and officinal part of Baizhi was carried out. We found that Hangbaizhi had the longest history and its yield field had changed. Hangzhou doesn’ t produce Baizhi any more. Baizhi had the widest function in the Ming dynast, but its applied scope has become narrow more and more since the Qing dynast and some funtion such as hemastation is out of use now. It has been found that the collecting time isn’ t same between the South and the North, we believe that such narration as "collected in Augest" and "collected in winter" reflected Baizhi collecting in the North after studying on documents.To fount out the producing history, production and marketing of Radix Angelica dahuricae, investigating at the spot and consulting the relating documents were carried out in Heinan ,Hebei, Zhejiang and Sichuan province. The results show that Chuanbaizhi is best in quality and largest in yield. Hangbaizhi has the longest history, but its yield is small.Eight compounds were isolated from Angelica dahurica (Fisch. ex Hoffm. ) .Benth. et Hook. f. var. formosana ( Boiss.) Shan et Yuan . Compoud I was identified as B - sitosterol , compoud II was isoimperatorin , compoud in was osthole , compoud IV was imperatorin, compoud V was xanthotoxin , compoud VI was byakangelicol .compoud VII was oxypeucedanin hydrate and compoud VI was scopoletin . Compoud I and III were extracted from Radix angelica dahuricae for the first time , while compoud V and compoud VIII were extracted from Angelica dahurica (Fisch. ex Hoffm. ) Benth. et Hook. f. var. formosana ( Boiss.) Shan et Yuan for the first time.The total content of coumarins in Baizhi was determined for the firsttime by UV. At the same time , the content of imperatorin , isoimperatorin and oxypeucedanin hydrate in different samples was carried out by HPLC .The results show that the harvest time , the processing method and the officinal position have great effect on the coumarin content. To provide scientific basis for clinical using, extraction of the total coumarin of Baizhi was carried out. Pharmacologic effect experiments have been carried out also for the first time. They show that the total coumarin of Baizhi has no distinct effect of inhibit inflammation and cann’ t significantly inhibit ear swelling induced by xylene in mice. It can decrease the rats’ pain caused by hot board and actic acid. The further study shows that isoimperatorin and imperatorin have the distinct effect of repress pain and are the main active ingredients of Baizhi. Pharmacology experiments show that the total coumarin of Baizhi, isoimperatorin, imperatorin and oxypeucedanin hydrate have distinct anti-spasticity effect, while byakangelicin has no effect.更多还原