基于抗肿瘤活性、HPLC、GC-MS指纹图谱的新疆阿魏属植物药用价值研究

Ferula is XinJiang precious medicinal material, and has unique advantages in the treatment of tumor, rheumatoid arthritis, stomach pain and other aspects.According to the smell , Ferulic is divided into “Smelly Ferulic ”and “Sweet Ferulic”, Ferula sinkiangensis and Ferula fukanensis are contained in 《Chinese Pharmacopoeia》，but they are on the verge of extinction.Ferula. conocaula、Ferula. lehmannii、Ferula. teterrima、Ferula. Krylovii are used as substitutes of 《Chinese Pharmacopoeia》species in XinJiang folk.But the research foundation was weak, it limited their development and utilization.Therefore, Firstly,We investigate the resource distribution and reserves of four kinds of Ferula plants;Secondly,We divide four kinds of Ferula plants root extracts into petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, methanol fraction，water fraction,Through the proliferation inhibition and apoptosis effects of the tumor cells (colon cancer ,liver cancer, gastric cancer) ,we determine the anti-tumor effects of Ferula plants; Through the proliferation inhibition effects of the normal liver cells, renal cells and acute toxicity study in mice ,we detect the safe dose range of Ferula;Thirdly,We establish HPLC, GC-MS fingerprint, Principal component analysis and cluster analysis are used to evaluate the quality of Ferula.Ferulic acid ,Farnesiferol A, Farnesiferol C are determined by HPLC method.By all of the data,We can screen out Ferula species of rich reserves, safe and effective in use, high effective constituents content from four kinds of Ferula plants.Our study can provide the basis for the rational use of Ferula plants in XinJiang region.

阿魏为新疆特色珍贵药材，在治疗肿瘤、风湿性关节炎、胃痛等方面有独特的优势，根据气味新疆民间分为“臭阿魏”和“香阿魏”，《中国药典》收载新疆阿魏和阜康阿魏均为臭阿魏，但二者已濒临灭绝。臭阿魏植物中还有圆锥茎、大果、托里、臭阿魏等在民间作为药典品种的代用品，但研究基础薄弱，无法合理开发应用。因此，本课题首先调查新疆4种“臭阿魏类”植物的资源分布，探明其蕴藏量；将4种阿魏根提取物分为石油醚、乙酸乙酯、正丁醇、甲醇、水等部位，进行对肿瘤细胞（肝癌、胃癌、结肠癌）增殖抑制、促凋亡的研究；进行对人正常肝细胞、肾细胞增殖抑制和小鼠急性毒性研究，明确阿魏的安全剂量范围。建立HPLC、GC-MS指纹图谱，采用主成分分析和聚类分析对阿魏质量进行综合评价。再采用HPLC法测定阿魏酸、法尼斯淝醇A、C含量。从4种臭阿魏中筛查出蕴藏量丰富、安全有效、有效成分含量高的品种，为新疆阿魏植物的合理利用提供依据。

新疆5种阿魏植物资源调查结果表明，大果阿魏基本灭绝；新疆阿魏、托里阿魏、臭阿魏、圆锥茎阿魏目前均只发现一个分布地点，其中臭阿魏的资源蕴藏量相对较大。新疆5种阿魏对人胃癌SGC-7901细胞、人宫颈癌HeLa细胞、人表皮癌A-431细胞等8种肿瘤细胞均有一定的增殖抑制作用；对CT-26结肠癌小鼠中，U-14宫颈癌小鼠进行研究，结果表明：臭阿魏、新疆阿魏抑制肿瘤效果较好。新疆5种阿魏对RAW264.7炎性细胞均有一定的抑制作用，小鼠耳肿胀、小鼠激光甩尾实验表明，臭阿魏、大果阿魏的抗炎镇痛作用较好。新疆5种阿魏对正常肝细胞、肾细胞的增殖抑制较弱，小鼠急性毒性实验表明，以临床用量的120倍剂量给药，新疆5种阿魏均无动物死亡，表明是比较安全的。建立新疆4种阿魏GC-MS指纹图谱。建立新疆5种阿魏HPLC指纹图谱，与人胃癌SGC-7901细胞的增殖抑制率进行双变量Pearson相关分析，表明新疆阿魏和臭阿魏中化合物为lehmannolol具有明显抗肿瘤作用。从植物资源、药理作用、化学成分三方面综合分析新疆5种阿魏，臭阿魏具有较大开发利用的价值，值得进一步深入研究。