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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張麗冠 | zh_TW |
| dc.contributor.advisor | Li-Kwan Chang | en |
| dc.contributor.author | 林友信 | zh_TW |
| dc.contributor.author | Yo-Hsin Lin | en |
| dc.date.accessioned | 2025-09-10T16:10:59Z | - |
| dc.date.available | 2025-09-11 | - |
| dc.date.copyright | 2025-09-10 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-07-29 | - |
| dc.identifier.citation | Abrol, V., Kushwaha, M., Arora, D., Mallubhotla, S., Jaglan, S., 2021. Mutation, chemoprofiling, dereplication, and isolation of natural products from Penicillium oxalicum. ACS Omega 6, 16266–16272.
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Oxalierpenes A and B, unusual indole-diterpenoid derivatives with antiviral activity from a marine-derived strain of the fungus Penicillium oxalicum. J. Nat. Prod. 85, 1880–1885. Zimmermann, B.M., Ngoc, T.T., Tzaras, D.-I., Kaicharla, T., Teichert, J.F., 2021. A bifunctional copper catalyst enables ester reduction with H2: expanding the reactivity space of nucleophilic copper hydrides. J. Am. Chem. Soc. 143, 16865–16873. Zuo, W., Kwok, H.F., 2021. Development of marine-derived compounds for cancer therapy. Mar. Drugs 19, 342. zur Hausen, H., O’Neill, F.J., Freese, U.K., Hecker, E., 1978. Persisting oncogenic herpesvirus induced by the tumour promotor TPA. Nature 272, 373–375. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99403 | - |
| dc.description.abstract | Epstein-Barr病毒 (Epstein-Barr virus, EBV)為人類第四型疱疹病毒，會感染90 %以上的人，主要會感染B細胞與上皮細胞，具有潛伏期及溶裂期兩種生活史。EB病毒的再活化與許多癌症及自體免疫疾病相關，目前相關疾病的治療主要依賴Acyclovir這類型的廣效抗病毒藥物，其針對溶裂期DNA複製達到抑制效果，但由於此類藥物無法根除病毒潛伏，後續仍會因病毒再活化而造成疾病復發或惡化。因此，開發能夠抑制病毒再活化的新型藥物顯得尤為迫切。近年來，海洋生物在天然藥物的研究領域中逐漸受到重視，因海洋環境的獨特性，造就這些生物產生許多具有藥用價值的次級代謝產物。本研究透過海洋軟體動物文蛤 (Meretrix lusoria) 之衍生真菌作為標的，旨在尋找具有抑制EB病毒再活化的化合物。首先，從文蛤 (Meretrix lusoria) 分離出26株真菌，其中有5株所產生的萃取物具有顯著的抑制EB病毒Rta的表現，然後選定其中2株進行後續分析，經過物種鑑定，確認此二真菌分別為Annulohypoxylon stygium及Penicillium oxalicum。透過大量培養獲取更多次級代謝物，並以相同的萃取方法進行處理，最終分別得到713.4 mg及813.5 mg之粗萃物。接著，結合Sephadex LH-20管柱層析及逆相高效液相層析 (RP-HPLC) 進行分離純化，同時在分離過程中持續追蹤抑制病毒再活化效果，最終得到三個化合物，分別為2-呋喃甲醇 (2-furanmethanol) 、5-羥甲基-2-呋喃甲酸 (5-hydroxymethyl-2-furoic acid) 及2-呋喃甲酸 (2-furoic acid) 。其中，2-呋喃甲醇的藥理活性較顯著，EC50和CC50分別為7.49 µM 和125 µM，SI值達16.7，並且會抑制病毒的極早期蛋白質Zta及早期蛋白質EA-D的表現，在15 µM濃度下能夠有效抑制病毒顆粒的生成。未來將聚焦於候選化合物之藥效機制，以期為新型抗EB病毒治療策略提供新的方向。 | zh_TW |
| dc.description.abstract | Epstein-Barr virus (EBV), also known as human herpesvirus 4, infects over 90% of the human population, primarily targeting B cells and epithelial cells with two distinct life cycle, latency and lytic phase. The reactivation of EBV is associated with numerous cancers and autoimmune diseases. Current treatments for related diseases mainly rely on broad-spectrum antiviral drugs like acyclovir, which inhibits lytic DNA replication. However, since these drugs cannot eradicate the latent virus, subsequent viral reactivation can lead to disease recurrence or exacerbation. Therefore, the development of novel drugs that can inhibit viral reactivation is particularly urgent. In recent years, marine Mollusca have gained increasing attention in the field of natural drug research. The unique marine environment has led these organisms to produce many secondary metabolites with medicinal value. This study targets the derived fungi of the marine Mollusca Meretrix lusoria, aiming to find compounds that inhibit EBV reactivation. Initially, 26 fungal strains were isolated from Meretrix lusoria. Among them, the extracts produced by 5 strains inhibited the expression of EBV Rta. Two of these strains were then selected for subsequent analysis. Through species identification, these two fungi were confirmed to be Annulohypoxylon stygium and Penicillium oxalicum. Mass cultivation was performed to obtain more secondary metabolites, which were processed using the same extraction method, yielding 713.4 mg and 813.5 mg of crude extracts, respectively. Then, separation and purification were conducted using Sephadex LH-20 column chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC), while continuously tracking the inhibitory effect on viral reactivation throughout the separation process. Three compounds were identified including 2-furanmethanol, 5-hydroxymethyl-2-furoic acid, and 2-furoic acid. Among them, 2-furanmethanol exhibited significant pharmacological activity, with an EC50 of 7.49 µM and a CC50 of 125 µM, resulting in a selectivity index (SI) of 16.7. 2-Furanmethanol also inhibited the expression of the viral immediate-early protein Zta and the early protein EA-D, and it effectively reduced the production of viral particles at a concentration of 15 µM. Future research will focus on the pharmacodynamic mechanism of the candidate compound, with the hope of providing a new direction for novel anti-EBV therapeutic strategies. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-10T16:10:59Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-10T16:10:59Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
摘要 ii Abstract iii 目次 v 表次 viii 圖次 ix 縮寫表 x 第一章 前言 1 1.1 EB病毒 (Epstein-Barr virus, EBV) 1 1.1.1 簡介 (Introduction) 1 1.1.2 組成及基因組 (Composition and genome) 1 1.1.3 生活史 (Life cycle) 2 1.2 EB病毒的相關疾病及治療 (EBV associated diseases and treatment) 3 1.3 天然藥物 (Natural products) 6 1.3.1 海洋真菌次級代謝物 (Secondary metabolic products of marine fungi) 7 1.3.2 文蛤 (Meretrix lusoria) 衍生真菌Annulohypoxylon stygium及Penicillium oxalicum之簡介 7 1.3.3 Annulohypoxylon stygium成分之文獻回顧 8 1.3.4 Penicillium oxalicum成分之文獻回顧 8 1.4 研究目的 8 第二章 材料與方法 10 2.1 衍生真菌培養及分離純化 10 2.2 真菌物種鑑定 (Species identification) 10 2.3 衍生真菌次級代謝物的取得及萃取 11 2.4 薄層層析 (Thin layer chromatography) 11 2.5 Sephadex LH-20管柱層析 (Sephadex LH-20 column chromatography) 12 2.6 逆向高效率液相層析 (Reversed-phase high-performance liquid chromatography, RP-HPLC) 12 2.7 核磁共振氫譜 (1H-NMR) 12 2.8 細胞株培養 (Cell culture) 13 2.9 EBV的溶裂期誘導 (Lytic induction of EBV) 13 2.10 細胞蛋白質萃取 (Protein extraction) 13 2.11 西方墨點法 (Western blot analysis) 14 2.12 細胞毒性測試 (Cytotoxicity test) 14 2.13 半效應濃度 (50% effective concentration, EC50) 14 2.14 半毒性濃度 (50% cytotoxic concentration, CC50) 15 2.15 選擇性指數 (Selective index, SI) 15 2.16 病毒顆粒DNA的萃取 (Extraction of viral particle DNA) 15 2.17 即時聚合酶連鎖反應 (Real-time polymerase chain reaction) 16 第三章 結果 17 3.1 Meretrix lusoria衍生真菌株的培養及純化 17 3.2 抗EBV再活化之次級代謝物的篩選 17 3.3 LYH 13及LYH 4的物種鑑定 18 3.4 Annulohypoxylon stygium抗EBV再活化的次級代謝物分析 18 3.5 Penicillium oxalicum抗EBV再活化的次級代謝物分析 19 3.6 2-furanmethanol、5-hydroxymethyl-2-furoic acid及2-furoic acid的抗EBV再活化分析 20 3.7 2-furanmethanol對病毒溶裂期的影響 20 3.8 2-furanmethanol 對病毒顆粒產生的影響 21 第四章 討論 22 4.1 衍生真菌粗萃物的獲取與篩選 22 4.2 抑制活性引導與層析法分析 22 4.3 具抑制EB病毒再活化的化合物之藥理測試 23 4.4 呋喃衍生物之結構活性關係與生合成 24 4.5 呋喃衍生物之藥用潛力 24 4.6 結論 25 第五章 圖表 27 參考文獻 85 附錄 99 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | EB病毒 | zh_TW |
| dc.subject | 溶裂期 | zh_TW |
| dc.subject | 文蛤 | zh_TW |
| dc.subject | 幽隱炭團菌 | zh_TW |
| dc.subject | 草酸青黴菌 | zh_TW |
| dc.subject | 2-呋喃甲醇 | zh_TW |
| dc.subject | 5-羥甲基-2-呋喃甲酸 | zh_TW |
| dc.subject | 2-呋喃甲酸 | zh_TW |
| dc.subject | Penicillium oxalicum | en |
| dc.subject | Meretrix lusoria | en |
| dc.subject | 2-furoic acid | en |
| dc.subject | 5-hydroxymethyl-2-furoic acid | en |
| dc.subject | 2-furanmethanol | en |
| dc.subject | Annulohypoxylon stygium | en |
| dc.subject | Epstein-Barr virus | en |
| dc.subject | lytic cycle | en |
| dc.title | 海洋真菌之幽隱炭團菌及草酸青黴菌的次級代謝物對EB病毒再活化的抑制 | zh_TW |
| dc.title | Inhibition of Epstein-Barr virus reactivation by secondary metabolites from marine fungi Annulohypoxylon stygium and Penicillium oxalicum | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 李宗徽 | zh_TW |
| dc.contributor.coadvisor | Tzong-Huei Lee | en |
| dc.contributor.oralexamcommittee | 陳日榮;李慶國;吳育騏 | zh_TW |
| dc.contributor.oralexamcommittee | Jih-Jung Chen;Ching-Kuo Lee;Yu-Chi Wu | en |
| dc.subject.keyword | EB病毒,溶裂期,文蛤,幽隱炭團菌,草酸青黴菌,2-呋喃甲醇,5-羥甲基-2-呋喃甲酸,2-呋喃甲酸, | zh_TW |
| dc.subject.keyword | Epstein-Barr virus,lytic cycle,Meretrix lusoria,Annulohypoxylon stygium,Penicillium oxalicum,2-furanmethanol,5-hydroxymethyl-2-furoic acid,2-furoic acid, | en |
| dc.relation.page | 104 | - |
| dc.identifier.doi | 10.6342/NTU202502254 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2025-07-30 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | 2030-07-23 | - |
| 顯示於系所單位： | 生化科技學系 | |
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