【作者】 王佳；

【导师】 张鹏；

【作者基本信息】 华中科技大学 ， 中药与天然药物学， 2020， 硕士

【摘要】 刺壳花椒（Zanthoxylum echinocarpum Hemsl.）是芸香科、花椒属藤本植物,主要分布在湖北、湖南、广东、广西、贵州等省,常见于海拔200-1000米的丛林中。刺壳花椒的药用部位是根皮,在鄂西鹤峰地区作三百棒入药,主要用于治疗类风湿性关节炎（RA）。目前,对刺壳花椒的药理活性以及化学成分的研究甚少。因此,本课题旨在阐明刺壳花椒的药效物质基础,为刺壳花椒在临床上的应用提供理论依据。通过多种柱层析方法,从刺壳花椒的根皮中共分离得到了59个化合物。通过多种波谱技术、改良Mosher法、铜靶单晶衍射等手段鉴定了这些化合物的结构。其中有17个香豆素类化合物（1-17）为新化合物,这些新化合物包括10个简单香豆素（1-10）、6个线型二氢呋喃香豆素（11-16）和1个角型二氢呋喃香豆素（17）。其他已知化合物包括:13个简单香豆素（18-30）、3个线型呋喃香豆素（31-33）、1个角型呋喃香豆素（34）、7个二氢呋喃香豆素（35-41）、6个香豆素糖苷（42-47）、6个木脂素（48-53）、3个木脂素糖苷（54-56）、2个生物碱（57-58）和1个其他类糖苷（59）。在已知化合物中,有19个化合物（26,29,30,36,38,39,40,41,42,43,45,46,47,48,50,51,52,54,58）为首次从花椒属中分离得到。本论文还对一株炭角菌属内生真菌Xylaria sp.DO1801的次生代谢产物进行了系统的研究。炭角菌属（Xylaria）属于子囊菌门炭角菌科（Xylariaceae）。目前,全球范围内,已发现超过300种该属的真菌。炭角菌属真菌的次生代谢产物非常丰富,包括细胞松弛素、生物碱、聚酮、萜类等。本研究从炭角菌属真菌Xylaria sp.DO1801的大米发酵物中分离得到了9个细胞松弛素（60-68）,包括一个新化合物（60）。本研究对化合物1-10,12,15-17,60-61进行了细胞毒活性研究。实验结果表明只有从刺壳花椒植物中分离的得到的化合物3对人肝癌细胞Hep3B和HepG2具有一定的细胞毒作用,其IC₅₀分别为31.80μM,16.54μM。此外,本课题对化合物1-10,12,15,17的抗炎活性进行了研究。通过脂多糖（LPS）诱导的RAW264.7细胞炎症模型,检测上述化合物对这类细胞的一氧化氮（NO）、肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）的释放的影响。实验结果表明,受试化合物均能显著抑制NO、TNF-α和IL-1β的释放,这说明这些化合物均有抗炎作用。更多还原

【Abstract】 Zanthoxylum echinocarpum Hemsl.,a vine of the family Rutaceae and Zanthoxylum,is mainly distributed in Hubei,Hunan,Guangdong,Guangxi,Guizhou and so on.It is commonly found in jungles at 200-1000 meters above sea level.The root bark of Z.echinocarpum is used to treat rheumatoid arthritis（RA）by the Tujia residents of western Hubei.Few investigations have been made on the pharmacological activity and chemical composition of Z.echinocarpum.Thus,the purpose of this research was to clarify the chemical composition of Z.echinocarpum and provide evidences for its further clinical application.A study on the 95% ethanol extract of the root bark of Z.echinocarpum led to the isolation of 59 compounds.Their structures were identified by extensive spectroscopic methods,modified Mosher ester analysis,X-ray diffraction and so on.17 simple coumarins and dihydrocoumarins were elucidated as new compounds.Among the known compounds,compounds 26,29,30,36,38,30,40,41,42,43,45,46,47,48,50,51,52,54 and 58 were separated for the first time in the genus.Xylaria is a member of the family of Xylariaceae.More than 300 species of Xylaria have been discovered worldwide,which are a great source of cytochalasins,alkaloids,polyketides,terpenoids and so on.A fungus of Xylaria,named Xylaria sp.DO1801,was isolated from the root of Damnacanthus officinarum.Its chemical composition was investigated.9 cytochalasins,including a new one（60）,were isolated from the ethyl acetate extract of the Xylaria sp.DO1801.The cytotoxicities of compounds 1-10,12,15-17,60-61 against several human tumor cell lines were evaluated by MTT method.The results showed that only 3exhibitted moderate cytotoxities against hepatocellular carcinoma Hep G2 and Hep3B with IC₅₀ values of 31.80 and 16.54μM,respectively.The anti-inflammatory effects of compounds 1-10,12,15 and 17 on LPS-induced RAW 264.7 macrophages were evaluated by the level of nitric oxide（NO）,tumor necrosis factor-α（TNF-α）and interleukin 1-β（IL-1β）.The results showed that all the tested compounds inhibited the production of NO,TNF-α,IL-1β,indicating these compounds exhibited anti-inflammatory effects.更多还原