KIB OpenIR  > 昆明植物所硕博研究生毕业学位论文
皱叶酸模根的化学成分及生物活性研究
李永祥
Thesis Advisor张颖君
Keyword皱叶酸模,化学成分,生物活性,网络药理学 Rumex crispus L., Chemical composition, Biological activity, Network pharmacology
Abstract本论文由三章构成,第一章为引言,介绍了皱叶酸模(Rumex crispus L.)的 研究进展;第二章介绍了皱叶酸模根的化学成分及生物活性研究;第三章讨论了 使用网络药理学的方法研究皱叶酸模根治疗湿疹的作用机制。 皱叶酸模是蓼科(Polygonaceae)酸模属(Rumex L.)的植物,根和根茎入药, 最早出现在《草木便方》一书中,被称作牛耳大黄,中药材名为土大黄,性寒, 苦中带有酸味,具有清热凉血、杀虫、通便等功效。前人对皱叶酸模根的工作主 要是对其粗提物进行药理活性研究,而化学成分的研究相对较少。本论文对皱叶 酸模的根开展了系统的化学成分和生物活性研究。利用多种现代色谱及波谱技术, 从该植物的甲醇提取物中分离鉴定 40 个化合物。采用 1D/2D 核磁共振波谱、质 谱、旋光、紫外、CD 谱以及 X-射线单晶衍射等方法对其化学结构进行鉴定,化 合物类型涉及蒽醌及其配糖体、萘及其配糖体、黄酮类和色原酮类等。其中蒽醌 类包括蒽醌苷元,氧苷蒽醌,碳苷蒽酮以及裂环蒽醌苷,通过外标法对其中的大 黄素和大黄素甲醚进行定量分析,结果显示皱叶酸模根中含有大黄素和大黄素甲 醚的含量分别为为 0.546 mg/g 和 1.548 mg/g;萘类主要是酸模素的苷类成分及萘 酮。其中有 4 个新化合物,包括一个裂环蒽醌苷和 3 个萘酮类成分。对新裂环蒽 醌苷提出可能的生物合成途径,它的形成可能是和 GedF(Geodin synthesis protein F)和 GedK(Geodin synthesis protein K)两个酶有关,它们共同催化了开环过程。 对分离得到的部分化合物进行了抗真菌、抗氧化、抗炎、抗肿瘤等活性评价。 结果显示化合物 emodin(9)对三种皮肤病真菌:絮状表皮癣菌(Epidermophyton floccosum)、红色毛癣菌(Trichophyton rubrum)、石膏样小孢子菌(Microsporum gypseum)有着较强的抑制作用,尤其是对絮状表皮癣菌(MIC50 = 2.467 ± 0.03 μM)石膏样小孢子菌(MIC50 = 4.673 ±0.077 μM),并且化合物 9 在 50 μM 浓度 条件下有微弱的抗炎作用。同时所选取的 4 个裂环蒽醌苷化合物对 5 株人类肿瘤 细胞抑制活性不明显。构效关系分析表明蒽醌类化合物的抗真菌(絮状表皮癣菌 和石膏样小孢子菌)及抗炎活性测试中蒽醌苷元的活性最强,特别是大黄素,氧 摘 要 II 苷和碳苷蒽酮类成分活性次之,裂环蒽醌苷成分可能是由于母核中 C-10 和 C-4a 位之间的键断开的原因,导致其活性下降。抗氧活性测试显示,黄酮类成分的活 性强于蒽醌类和萘类。 运用网络药理学及分子对接等手段,探讨了皱叶酸模根治疗湿疹(eczema) 的作用机制,利用 Cytoscape 3.6.1 软件构建皱叶酸模活性成分-靶点网络、蛋白 相互作用(PPI)网络,并通过 CytoNCA 插件功能构建疾病-成分-靶点网络,筛 选出皱叶酸模根治疗湿疹的核心靶点,最后使用 R3.6.3 软件进行 GO 和 KEGG 通路富集分析,预测可能的作用机制,并绘制 GO 和 KEGG 气泡图进行数据可 视化。得出关键基因主要是 STAT3、PTGS2、PPARG、AKT1、HRAS、PTPRC、 ALB、SRC、ERBB2 等。其中起主要作用的活性成分为大黄素甲醚、大黄酚、1,8- 二羟基-3-甲基-9-蒽酮等化合物。将核心成分 与 9 个核心靶点的分子对接结果展 示了核心靶点与核心成分之间良好的结合活性,这也印证了皱叶酸模根治疗湿疹 的科学性。本论文的研究结果将为皱叶酸模的进一步利用提供一定的科学基础。; This dissertation is composed of three chapters. The first chapter, we reviewed the phytochemistry, biological property of Rumex crispus L. Reported in chapte r two mainly described the chemical and bioactive investigation on the roots of R. crispus. In the final chapter, we use network pharmacology approach to explore the mechanism of action of the roots of R. crispus in the treatment of eczema. Rumex crispus L. is a perennial herb in the Polygonaceae family, the roots and rhizomes of which can be used as medicine. R. crispus, with the effects of clearing heat and detoxifying, hemostasis, laxative and killing worms. This thesis is systematic study of the chemical composition and biochemistry of the roots of R. crispus. Using various modern chromatographic and spectroscopic techniques, 40 compounds were isolated and purified from the methanolic extract of this plant. Chemical structures were identified by 1D/2D NMR spectroscopy, mass spectrometry, UV, CD spectroscopy and X-ray single crystal diffraction, involving anthraquinones and their ligands, naphthalenes and their ligands, flavonoids, chromones and other structural types. The anthraquinones included glycosidic anthraquinones, oxyglucoside and carboside anthraquinones and seco-anthraquinone glucosides. The quantification of emodin and physcion in root of R. crispus by external standard method revealed that contained approximately 0.546 mg/g and 1.548 mg/g of emodin and physcion, respectively. There were four new compounds, including one seco-anthraquinone glycoside and three naphthone components. A possible synthetic pathway for the new seco-anthraquinone glycoside is proposed, and its formation may be related to two enzymes, GedF (Geodin synthesis protein F) and GedK (Geodin synthesis protein K), which together catalyze the ring-opening process. Some of the isolated compounds were evaluated for their antifungal, antioxidant, anti-inflammatory and antitumor activities. The results showed that compound 9 (emodin) had a strong inhibitory effect against three fungi (Flocculus epidermidis, Abstract IV Trichophyton rubrum and Microsporum gypseum), especially against F. epidermidis (MIC50 = 2.467 ± 0.03 M) and M. gypseum (MIC50 = 4.673 ± 0.077 M), as well as a weak anti-inflammatory effect at a concentration of 50 μM. In contrast, the four selected seco-anthraquinone glycosides showed no apparent inhibitory activity against these five human tumor strains. Structure-activity relationships showed that the glycoside anthraquinones had the strongest antifungal and anti-inflammatory activity, especially emodin, followed by the oxyglucoside and carboside anthraquinone components. In addition, it is probably due to a bond break between the C-10 and C-4a positions in the parent nucleus that the activity of seco-anthraquinone glycosides has decreased. The results of antioxidant activity tests showed that anthraquinones and naphthalenes were less active than the flavonoid comp
Language中文
2022-05
Degree Grantor中国科学院大学
Document Type学位论文
Identifierhttp://ir.kib.ac.cn/handle/151853/75117
Collection昆明植物所硕博研究生毕业学位论文
Recommended Citation
GB/T 7714
李永祥. 皱叶酸模根的化学成分及生物活性研究[D]. 中国科学院大学,2022.
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