臺灣博碩士論文加值系統

背景：乾燥症為常見的自體免疫疾病，主要特徵為口乾和眼乾，嚴重影響患者的生活品質。中西整合醫療已被用於提高療效並減少副作用，中藥SS1複方已在細胞、動物模式及臨床試驗顯示其對乾燥症具療效，本研究進一步探討其有效成份。
方法：濃縮中藥複方SS1通過高效液相色譜法質量檢測、液相層析與串聯質譜和建立的資料庫對其中的植物化學成分進行鑑定。利用 Schrödinger平台作為主要運算工具，評估IL-17在乾燥症的潛在治療標靶。各活性成分和參考化合物進行了對接分析、ADMET預測和分子動力學模擬，以評估受體-配體複合物的穩定性，並分析蛋白質配體相互作用期間的波動和構象變化。
結果：高效液相色譜測試確認了SS1藥方的品質；液相層析與串聯質譜鑑定出SS1內含90種化合物；分子對接研究揭示了SS1粉末萃取物中的14種化合物在特定殘基處表現出比參考配體更高的Glide分數和MMGBSA值。這些化合物對特定殘基具有較強的結合親和力，且大多數不違反 Lipinski五法則。此外，分子動力學模擬的結果顯示：與參考配體相比，候選化合物和受體的穩定性較高。ADMET分析顯示：有6種成份在藥物研發中具有進一步研究的藥物適用性。
結論：中藥複方SS1所含生物活性成分可能是在開發IL-17抑制劑方面具有潛力的先導化合物，為乾燥症及其相關併發症提供了潛在的治療可能。

Background: Sjögren's syndrome is a common autoimmune disease, primarily characterized by dry mouth and dry eyes and significantly impacts patients's quality of life. Integrated medicine has been used to increase treatment effectiveness and reduce side effects. The traditional Chinese medicine SS1 remedy has demonstrated efficacy in treating Sjögren's syndrome through evidence from in vitro, in vivo and clinical trials.
Materials and Methods: The traditional Chinese medicine SS1 remedy was extracted and subjected to HPLC quality testing. Phytochemicals in SS1 were identified by using LC‒MS/MS and a built database. The Schrödinger platform was utilized as the primary computational tool to evaluate the potential therapeutic targets of IL-17 for Sjögren's syndrome. The bioactive components and reference compounds were subjected to docking analysis, ADMET prediction, and molecular dynamics simulation to assess the stability of the receptor‒ligand complex and analyze fluctuations and conformational changes during protein‒ligand interactions.
Results: HPLC analysis confirmed the quality of the SS1 remedy. LC‒MS/MS identified 90 compounds in SS1. Molecular docking studies revealed that selected compounds within the SS1 powdered extract exhibited higher glide scores and MMGBSA values compared to reference ligands at specific residues. These compounds exhibit strong binding affinity to specific residues, with most of them not violating the Lipinski’s rule of five. Furthermore, the results from the molecular dynamic simulation demonstrated the stability of the candidates and receptors compared to that of the reference ligands. ADMET analysis indicated that the selected ligands exhibited drug-like suitability for further investigation in new drug development.
Conclusion: The SS1 remedy and its various bioactive components could be promising lead compounds for IL-17 inhibitors, providing potential treatments for Sjögren's syndrome and its related complications.

Table of contents

Chapter 1. INTRODUCTION 1
Chapter 2. LITERATURE REVIEW 3
2.1. Sjögren's syndrome and interleukin 17 (IL-17) 3
2.1.1. Overview about Sjögren's syndrome 3
2.1.2. Interleukin 17 (IL-17) and its receptor 6
2.2. Sjögren's syndrome in Traditional Chinese Medicine (TCM) 7
2.3. SS1 remedy and Sjögren's syndrome 9
Chapter 3. MATERIALS AND METHODS 13
3.1. Experiments 13
3.1.1. SS1 medica materials and preparation 13
3.1.2. SS1 chemical quantifications 14
3.1.3. Identification of the extract composition by LC‒MS/MS 18
3.2. Computations 20
3.2.1. Molecular docking 20
3.2.2. Pharmacokinetics and pharmacology prediction 21
3.2.3. Molecular Dynamics Simulations (MDs) 21
Chapter 4. RESULTS 23
4.1. Experiments 23
4.1.1. Quantitative and qualitative analysis of SS1 components using HPLC 23
4.1.2. Phytochemical compounds of SS1 remedy 23
4.2. Computations 31
4.2.1. Docking analysis 31
4.2.2. ADMET analysis 47
4.2.3. Molecular Dynamics simulation (MDs) 55
Chapter 5. DISCUSSION 62
Chapter 6. CONCLUSION 70

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