本文選題：桂枝加芍藥湯 + 抗炎活性成分　； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：中藥方劑活性成分發(fā)現(xiàn)是中藥現(xiàn)代化研究的重要內(nèi)容。目前,中藥活性成分發(fā)現(xiàn)的主要方法有系統(tǒng)分離法、活性導(dǎo)向法、生物色譜法等,前兩種方法研究周期長(zhǎng)、耗時(shí)耗力、命中率低,生物色譜法可以從混合物中快速發(fā)現(xiàn)含量較高的潛在活性成分,但可能會(huì)忽略某些微量活性成分。為克服以上研究方法的不足之處,本論文通過(guò)采用活性指數(shù)方法評(píng)價(jià)中藥及其組分中各成分對(duì)其活性的貢獻(xiàn),從而預(yù)測(cè)其中潛在活性成分,并將該研究思路用于仲景方桂枝加芍藥湯中抗炎活性成分的快速發(fā)現(xiàn)。桂枝加芍藥湯出自于《傷寒論》,由桂枝、白芍、生姜、大棗和甘草組成,具有溫脾和中,緩急止痛的功效。臨床上主要用于治療腹?jié)M引起的脹痛,還可以治療頑固性菌痢,十二指腸球部潰瘍,結(jié)核性腹膜炎等疾病。目前該方的藥效物質(zhì)基礎(chǔ)尚不清楚。本論文以桂枝加芍藥湯為研究對(duì)象,以方劑中抗炎活性成分的快速發(fā)現(xiàn)為研究目標(biāo),具體研究如下：采用液相色譜-四級(jí)桿飛行時(shí)間質(zhì)譜(LC-Q-TOF-MS)和液相色譜-離子阱質(zhì)譜(LC-IT-MS)聯(lián)用方法對(duì)桂枝加芍藥湯總提物中化學(xué)成分進(jìn)行了分析。共檢測(cè)到72個(gè)化合物,鑒定和推測(cè)了其中54個(gè)化合物結(jié)構(gòu),主要類型包括單萜苷類、三萜皂苷類、黃酮及其苷類和有機(jī)酸及其苷類。采用大孔樹(shù)脂和制備液相色譜方法將桂枝加芍藥湯總提物分段制備成64個(gè)組分。利用LC-IT-MS對(duì)各個(gè)組分的化學(xué)成分進(jìn)行表征,一共檢測(cè)到903個(gè)化合物。采用細(xì)菌脂多糖(LPS)誘導(dǎo)小鼠巨噬細(xì)胞RAW264.7炎癥模型,對(duì)桂枝加芍湯湯組分的抗炎活性進(jìn)行評(píng)價(jià)。最后整合組分的化學(xué)信息和藥理信息,計(jì)算各成分的活性指數(shù),發(fā)現(xiàn)61個(gè)化合物有較高的活性指數(shù)值,推測(cè)這些化合物可能是潛在的抗炎活性成分。為了驗(yàn)證預(yù)測(cè)結(jié)果,對(duì)其中8個(gè)化合物進(jìn)行了LC-MS導(dǎo)向的半制備液相色譜分離制備,采用NMR譜鑒定其結(jié)構(gòu),利用LPS誘導(dǎo)小鼠巨噬細(xì)胞RAW 264.7的炎癥模型進(jìn)行抗炎活性驗(yàn)證。研究發(fā)現(xiàn),8個(gè)化合物均有良好的抗炎活性,其中6個(gè)化合物的抗炎活性明顯強(qiáng)于陽(yáng)性藥吲哚美辛。此外,3個(gè)化合物的抗炎活性為首次報(bào)道。本研究結(jié)果表明活性指數(shù)方法能快速有效地發(fā)現(xiàn)中藥方劑中的抗炎活性成分。
[Abstract]:The discovery of active components of traditional Chinese medicine prescription is an important content in the modernization of traditional Chinese medicine. At present, the main methods for the discovery of active components of traditional Chinese medicine include systematic separation method, active guidance method, biochromatographic method, etc. The first two methods have long research period, time-consuming and labor-consuming, low hit rate, etc. Biochromatographic method can quickly find the potential active components with high content in the mixture, but some trace active components may be neglected. In order to overcome the shortcomings of the above research methods, this paper uses the activity index method to evaluate the contribution of each component of traditional Chinese medicine and its components to its activity, so as to predict the potential active components. The research idea was applied to the rapid discovery of anti-inflammatory active components in Zhongjing Fang Guizhi Jiaoxiao decoction. Guizhi + Shaoyao decoction, composed of Cinnamon, Radix Paeoniae Alba, Ginger, Jujube and Glycyrrhiza uralensis, has the effect of warming the spleen and relieving pain. It is mainly used to treat distending pain caused by abdominal fullness, obstinate bacillary dysentery, duodenal bulbar ulcer, tuberculous peritonitis and so on. At present, the substance basis of the prescription is not clear. In this paper, Guizhijiaoxiao decoction was taken as the research object, and the rapid discovery of anti-inflammatory active components in the prescription was taken as the research goal. The main results are as follows: LC-Q-TOF-MS) and LC-IT-MS) were used to analyze the chemical constituents in the total extract of Guizhijiaoxiao decoction. A total of 72 compounds were detected and 54 of them were identified and speculated, including monoterpene glycosides, triterpenoid saponins, flavonoids and their glycosides, organic acids and their glycosides. The total extract of Guizhijiaoxiao decoction was prepared into 64 components by macroporous resin and preparative liquid chromatography. The chemical constituents of each component were characterized by LC-IT-MS and 903 compounds were detected. The inflammation model of mouse macrophage RAW264.7 was induced by lipopolysaccharide (LPS), and the anti-inflammatory activity of Guizhijiazhao decoction was evaluated. Finally, the chemical information and pharmacological information of the components were integrated to calculate the activity index of each component. It was found that 61 compounds had higher activity index values, which suggested that these compounds might be potential anti-inflammatory components. In order to verify the predicted results, eight of the compounds were separated and prepared by LC-MS directed semi-preparative liquid chromatography. Their structures were identified by NMR. The anti-inflammatory activity of LPS-induced mouse macrophage RAW 264.7 inflammatory model was verified. It was found that all of the eight compounds had good anti-inflammatory activity, and six of them had stronger anti-inflammatory activity than indomethacin. In addition, the anti-inflammatory activities of three compounds were reported for the first time. The results show that the active index method can quickly and effectively find the anti-inflammatory components in traditional Chinese medicine prescriptions.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R284

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