2014-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/713609摘要：中藥研究近年受到國際重視，代謝體學提供一個中藥化學物質分析及其在生物中作用的的全面研究。代謝體學也可了解中藥各成分在體內交互作用，可同時了解中藥在體內作用、包括副作用和毒性亦可以利用同一平台完成，可大為縮減中藥作為新藥開發所需 時間。 本研究已完成各種不同山梔子處理方法之製備之有效成分分析,未來目標將致力(1)以代謝體為基礎評估中草藥在體內正常和疾病狀況下,biotransformation 的變化;(2) 以代謝體為基礎瞭解中草藥在疾病狀況下對人體代謝的影響。本研究以山梔子為代表，藉急性和性兩種誘發出血性膀胱炎的動物實驗模式，利用代謝體學研究方法，了解山梔子在生物體代謝情形、生物作用、可能副作用。 本研究主要目的為使用山梔子此一常見中藥不同前處理方式，並以不同方式誘發出血性膀胱炎作為研究方向， 以代謝體學研究模式了解相關中藥開發及其療效評估。本研究完成後對出性膀胱炎致病機轉了解有所助益，山梔子對出血性膀胱炎的療效有所了解，副作用有所探討，且嘗試了解山梔子在體內真正最有效之活性成分為何，做為未來新藥開發努力的方向。<br> Abstract: Cyclophosphamide (CP) is a widely used chemotherapeutic agent that causes acute hemorrhagic cystitis. Although of the advanced prevention protocol, hemorrhagic cystitis is still a common and severe complication of the usage of cyclophosphamide. Ketamine, was originally synthesized for use as a dissociative anesthetics. The recreational use of ketamine has raised concerns worldwide. ketamine dependence leads to the development of LUTS that resemble interstitial cystitis. The pathophysiology of ketamine associated hemorrhagic cystitis has not been understood. Chinese herbal drugs have aroused much interest recently especially due to its superiority in the treatment of complicated disease. Gardenla Jasminoides Ellis is one component of Chinese traditional medication for the treatments of hemorrhagic cystitis. Several bioactive compounds have been found such as crocetin or geniposide.The vast number of metabolites typically present in natural products and their huge dynamic range results in the complex of many possibility bioactive natural compound. The capacity of metabolomics to measure numerous chemicals simultaneously and detect subtle differences among sample groups makes it a powerful discovery tool. Plant metabolomics deals with qualitative and quantitative analysis from plant and covers targeted metabolomics analysis, profiling and fingerprint. Ultra-performance liquid chromatography- tandem mass spectrometry (UPLC-tandem-MS) techniques and in the development of new multivariate data analysis methods have led to a giant leap in knowledge about the plant metabolomics and its response to systemic biology Metabolomics is a crucial tool for (1) identification of active compounds and quantitative prediction of bioactivity, (2) the identification of efficacy and action of herbal medicine, (3) evaluation of herbal biotransformation, (4) safety and toxicity of herbal medicine assessment. There are three parts in our study. In the first year, we have evaluated the traditional herbal decoction, the commercial extract of Gardenla Jasminoides Ellis and search the contents of bioactive constituents by UPLC-tandem-MS. Secondly, we will try a metabolomics approach base on UPL-C tandem- MS to characterize the metabolic profile associated with acute administration of cyclophasmide or chronic administration of ketamine-induced hemorrhagic cystitis. We will try to find the metabolic pathways and potential biomarkers related to hemorrhagic cystitis. Thirdly, we will assess the therapeutic effects and mechanisms of Gardenla Jasminoides Ellis in treatment of hemorrhagic cystitis. We will also apply the metabolomics approach to explore the safety and toxicity of Gardenla Jasminoides Ellis. Metabolomics provide a holistic alternative to tackle the challenges in identifying novel chemicals from Chinese herbal products and studying complex interactions between phytochemicals and biological system. This information can be used to identify novel and improved diagnostic and therapeutic targets that might prevent, or ameliorate the severe complications of acute usage of cyclophosphanmide or the chronic usage of ketamine induced hemorrhagic cystitis.