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研究生:簡良軒
研究生(外文):CHIEN, LIANG-HSUAN
論文名稱:桑樹桑黃對新冠病毒的抑制及其併發症之研究
論文名稱(外文):Study on the inhibition of Sanghuangporus sanghuang on SARS-CoV-2 and its complications
指導教授:黃冠中黃冠中引用關係黃文欽
指導教授(外文):HUANG, GUAN-JHONGHUANG, WEN-CHIN
口試委員:黃冠中黃文欽張永勳陳顯榮鄧正賢
口試委員(外文):HUANG, GUAN-JHONGHUANG, WEN-CHINCHANG, YUAN-SHIUNCHEN, HSIEN-JUNGDENG, JENG-SHYAN
口試日期:2023-05-25
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:中國藥學暨中藥資源學系博士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2023
畢業學年度:111
語文別:中文
論文頁數:226
中文關鍵詞:桑樹桑黃新型冠狀病毒特發性肺纖維化慢性腎衰竭前列腺癌
外文關鍵詞:Sanghuangporus sanghuangSARS-CoV-2Idiopathic pulmonary fibrosisChronic kidney diseaseProstate cancer
DOI:https://doi.org/10.1016/j.biopha.2022.113434; https://doi.org/10.1016/j.biopha.2023.115080
ORCID或ResearchGate:orcid.org/0000-0002-8737-3410
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第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究
2019年,於中國武漢發現了新型冠狀病毒-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),造成新型冠狀病毒疾病coronavirus disease-2019 (COVID-19) 導致嚴重的全球大流行。Angiotensin-converting enzyme 2 (ACE2) 與SARS-CoV-2的棘蛋白結合,使病毒能夠穿過細胞膜並進入細胞;transmembrane serine protease 2 (TMPRSS2) 修飾SARS-CoV-2,能促進病毒進入細胞。因此,ACE2和TMPRSS2是預防SARS-CoV-2感染的重要指標。桑樹桑黃 (Sanghuangporus sanghuang;SS) 是一種傳統中藥,被證明具有抗腫瘤、抗氧化、抗發炎、抗糖尿病、肝臟保護、神經保護和免疫調節的特性。本研究證明SS在無細胞毒性或器官損傷的情形下,可降低細胞和小鼠模型中ACE2和TMPRSS2的表現。藉由IHC染色評估肝臟和腎臟切片,確認ACE2和TMPRSS2的表現有明顯減少。由西方墨點法測試,SS的酚類化合物hispidin、3,4-dihydroxybenzalacetone (DBA)、protocatechuic acid (PAC)、protocatechualdehyde (PAD)和caffeic acid (CA能降低ACE2和TMPRSS2的表現。綜合結果表示,SS及其酚類化合物具有預防SARS-CoV-2感染的潛力。

第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用
特發性肺纖維化 (idiopathic pulmonary fibrosis;IPF) 是一種特定的慢性、進行性、纖維化間質性肺炎,其病因不明。先前的研究已證明SS具有多種活性,包括免疫調節、肝保護、抗腫瘤、抗糖尿病、抗發炎和神經保護作用。本研究使用Bleomycin (BLM) 誘導IPF小鼠模型,闡明SS在改善IPF中的潛在益處。在第1天給予BLM以建立IPF小鼠模型,並連續管灌給予SS 21天。由H&E、Masson Trichrom Stain和PAS stain評估肺臟切片,結果顯示,SS在形態學上能顯著減少肺臟受損並顯著降低Collagen的產生。SS能顯著降低促發炎細胞因子 (TNF-α、TGF-β、IL-1β和IL-6) 和MPO並顯著提升GSH的表現量。由西方墨點法測試,驗證SS能降低發炎因子 (TWEAK、iNOS和COX-2)、MAPK (p-JNK、p-ERK和p-p38)、纖維化關鍵分子 (TGF-β、Smad3、fibronectin、collagen、α-SMA、MMP2和MMP9)、凋亡 (p53、p21和Bax) 和自噬 (Beclin-1、LC3A/B-I/II和p62);且能顯著提升Bcl-2、caspase 和抗氧化劑 (catalase、GPx3和SOD-1)。透過調節CaMKK/AMPK/Sirt-1和Keap-1/HO-1/Nrf-2路徑來減緩IPF。綜合結果表示,SS具保護肺臟並防止肺臟纖維化的活性與潛力。

第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究
慢性腎衰竭 (chronic kidney disease;CKD) 是一種臨床症候群,由腎臟功能和/或結構明顯改變所引起,其特點是不可逆轉、緩慢且漸進性發展。另一個重要的方面是,該病理表現代表了更高的併發症和死亡風險,特別是心血管相關的風險。Cisplatin是一種抗腫瘤藥物,已被廣泛用於治療固態腫瘤,雖然副作用包括耳毒性、胃毒性、骨髓抑制和過敏反應,然而在臨床應用上卻受限於腎毒性的副作用。
先期研究結果,SS證實具有抗腫瘤、抗氧化、抗發炎、降血糖、肝保護、神經保護和免疫調節等多種特性。在本文中,藉由H&E、Masson Trichrom Stain和PAS stain來評估腎臟切片,確認在形態學上有顯著的減少腎臟受損並能顯著降低纖維化的情形。SS能顯著降低BUN (blood urea nitrogen)、creatinine和促發炎細胞因子 (TNF-α、TGF-β、IL-1β和IL-6)。對SS處理的樣品進行的西方墨點法測試,驗證其能降低發炎因子 (TWEAK、iNOS、COX-2、NF-κB和IκB-)、MAPK (p-JNK、p-ERK和p-p38) 和凋亡 (p53、p21和Bax);且能顯著提升Bcl-2、caspase 3和抗氧化劑 (catalase、GPx3和SOD-1)。透過調節CaMKK/AMPK/Sirt-1和Keap-1/HO-1/Nrf-2路徑來減緩CKD。綜合結果表示,SS具有保護腎臟的藥理活性,防止CKD的潛力。

第四部分 桑樹桑黃對前列腺癌之藥理活性研究
癌症是2021年臺灣的十大死因之首。前列腺癌 (prostate cancer;PCa)在十大癌症死亡率中排名第五。PCa被認為是男性的主要健康問題,其特點是前列腺腺體內異常分裂的細胞,導致前列腺異常增大。臨床和病理學研究明確表明,androgen receptor (AR) 是促進前列腺正常發育和功能以及PCa生長、存活和致命進展的重要因素。值得注意的是,雄激素合成和AR信號路徑的阻斷對PCa治療具有益處。
SS在先前研究中已被發現具有多種生物活性。並且在本文中,證實SS能顯著抑制PCa細胞的遷移。利用流式細胞儀驗證SS能顯著提升PC-3及LNCaP細胞凋亡的作用。對SS進行西方墨點法的測試,驗證其能顯著降低抑制細胞凋亡 (Bcl-2)、脂質生成及膽固醇合成 (AR、SREBP-1、FASN和SREBP-2)、發炎因子 (NF-κB、COX-2和p-AMPK) 及基質金屬蛋白酶 (MMP2和MMP9) 的蛋白表現,且能顯著提升細胞凋亡 (Bax、c-caspase 3和c-PARP) 和基質金屬蛋白酶抑制劑 (TIMP-1和TIMP-2) 的蛋白表現。在裸鼠模型中,證明SS在沒有細胞毒性或器官損傷的情形下,可以顯著縮小腫瘤體積。藉由IHC染色法證實SS可以顯著降低Ki-67且顯著提升c-caspase 3的陽性反應。綜合結果表示,SS具有抗PCa的藥理活性。
Part 1. Study on the potential of Sanghuangporus sanghuang and its components as COVID-19 spike protein receptor binding domain inhibitors
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to the most severe global pandemic, which began in Wuhan, China. Angiotensin-converting enzyme 2 (ACE2) combines with the spike protein of SARS-CoV-2, allowing the virus to cross the membrane and enter the cell. SARS-CoV-2 is modified by the transmembrane protease serine 2 (TMPRSS2) to facilitate access to cells. Accordingly, ACE2 and TMPRSS2 are targets of vital importance for the avoidance of SARS-CoV-2 infection. Sanghuangporus sanghuang (SS) is a traditional Chinese medicine that has been demonstrated to have antitumor, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and immunomodulatory properties. In this paper, we demonstrated that SS decreased ACE2 and TMPRSS2 expression in cell lines and a mouse model without cytotoxicity or organ damage. Liver and kidney sections were confirmed to have reduced expression of ACE2 and TMPRSS2 by immunohistochemistry (IHC) assessment. Then, hispidin, 3,4-dihydroxybenzalacetone (DBA)、protocatechuic acid (PAC)、protocatechualdehyde (PAD) and caffeic acid (CA) phenolic compounds of SS, were also tested and verified to reduce the expression of ACE2 and TMPRSS2. In summary, the results indicate that SS and its phenolic compounds have the latent capacity for preventing SARS-CoV-2 infection in the future. 

Part 2. Evaluation of Lung Protection of Sanghuangporus sanghuang through TLR-4/NF-κB/MAPK, Keap-1/Nrf-2/HO-1, CaMKK/AMPK/Sirt-1 and TGF-β/Smad3 Signal Pathways Mediating Apoptosis and Autophagy
Idiopathic pulmonary fibrosis (IPF) is a type of interstitial pneumonia characterized by chronic and progressive fibrosis with an unknown etiology. Previous pharmacological studies have shown that Sanghuangporus sanghuang possesses various beneficial properties including immunomodulatory, hepatoprotective, antitumor, antidiabetic, anti-inflammatory, and neuroprotective effects. This study used a BLM-induced IPF mouse model to illustrate the possible benefits of SS in ameliorating IPF. BLM was administered on day 1 to establish a pulmonary fibrosis mouse model, and SS was administered through oral gavage for 21 d. Hematoxylin and eosin (H&E) and Masson’s trichrome staining results showed that SS significantly reduced tissue damage and decreased fibrosis expression. We observed that SS treatment resulted in a substantial lowering in the level of pro-inflammatory cytokines like TGF-β, TNF-α, IL-1β, and IL-6 as well as MPO. In addition, we observed a notable increase in glutathione (GSH) levels. Western blot analysis of SS-treated samples showed that it reduces inflammatory factors (TWEAK, iNOS, and COX-2), MAPK (p-JNK, p-ERK, and p-p38), fibrosis-related molecules (TGF-β, Smad3, fibronectin, collagen, α-SMA, MMP2, and MMP9), apoptosis (p53, p21, and Bax), and autophagy (Beclin-1, LC3A/B-I/II, and p62), and notably increases caspase 3, Bcl-2, and antioxidant (catalase, GPx3, and SOD-1) levels. SS alleviates IPF by regulating the TLR-4/NF-κB/MAPK, Keap-1/Nrf-2/HO-1, CaMKK/AMPK/Sirt-1, and TGF-β/Smad3 pathways. These results suggest that SS has pharmacological activity that protects the lungs and has the potential to improve pulmonary fibrosis.

Part 3. Study on the protective effects and mechanisms of Sanghuangporus sanghuang on chronic kidney disease
Chronic kidney disease (CKD) is a clinical syndrome characterized by significant changes in kidney function and/or structure, which are irreversible, slow, and progressive. Another important aspect is that the pathological manifestations represent a higher risk of complications and death, particularly cardiovascular-related risks. Cisplatin is an antitumor drug that has been widely used to treat solid tumors. Although its side effects include ototoxicity, gastric toxicity, bone marrow suppression, and allergic reactions, its clinical application is limited by the nephrotoxic side effects.
Sanghuangporus sanghuang (SS) is a traditional Chinese medicine with anti-tumor, antioxidant, anti-inflammatory, hypoglycemic, hepatoprotective, neuroprotective, and immunomodulatory properties. In this study, kidney sections were evaluated by H&E, Masson Trichrome Stain, and PAS stain to confirm a significant reduction in kidney damage and fibrosis morphologically. SS significantly reduced BUN, creatinine, and pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Western blot analysis of SS-treated samples demonstrated a decrease in inflammatory factors (TWEAK, iNOS, COX-2, NF-κB, and IKB), MAPKs (p-JNK, p-ERK, and p-p38), and apoptosis (p53, p21, and Bax), and a significant increase in Bcl-2, caspase 3, and antioxidants (catalase, GPx3, and SOD-1). CKD was mitigated through the regulation of the CaMKK/AMPK/Sirt-1 and Keap-1/HO-1/Nrf-2 pathways. These results collectively demonstrate that SS has pharmacological activity in protecting the kidney and has the potential to prevent chronic kidney disease. 

Part 4. Pharmacological Study of Sanghuangporus sanghuang on Prostate Cancer
Cancer is the leading cause of death in Taiwan in 2021. Prostate cancer (PCa) ranks fifth among the top ten cancer mortality rates. Prostate cancer is considered a major health issue in males, characterized by abnormal cell proliferation in the prostate gland, leading to abnormal prostate enlargement. Clinical and pathological studies clearly indicate that the androgen receptor (AR) plays a crucial role in promoting normal prostate development and function and the growth, survival, and lethal progression of prostate cancer. Notably, the inhibition of androgen synthesis and the blockade of the AR signaling pathway have shown benefits in the treatment of prostate cancer.
Based on previous studies, Sanghuangporus sanghuang has been found to possess various biological activities, making it a potential dietary supplement with anti-tumor, antioxidant, anti-inflammatory, blood glucose-lowering, hepatoprotective, neuroprotective, and immune-modulating properties. In this study, SS significantly inhibits the migration of prostate cancer cells. Flow cytometry analysis demonstrated that SS significantly enhances apoptosis in PC-3 and LNCaP cells. Western blot analysis of SS revealed its significant downregulation of AR, anti-apoptotic protein (Bcl-2), lipogenesis and cholesterol synthesis markers (SREBP-1, FASN, and SREBP-2), inflammatory factors (NF-κB, COX-2, and p-AMPK), and matrix metalloproteinases (MMP2 and MMP9), as well as its significant upregulation of pro-apoptotic markers (Bax, c-caspase 3, and c-PARP) and matrix metalloproteinase inhibitors (TIMP-1 and TIMP-2). In a nude mouse model, it was demonstrated that SS significantly reduces tumor volume without exhibiting cytotoxicity or organ damage. Immunohistochemical staining confirmed that SS significantly decreases Ki-67 expression and significantly increases c-caspase 3 expressions. Collectively, these results indicate that SS possesses pharmacological activity against prostate cancer.
謝辭 I
中文摘要 II
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究 II
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 III
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究 IV
第四部分 桑樹桑黃對前列腺癌之藥理活性研究 V
英文摘要 VI
Part 1. Study on the potential of Sanghuangporus sanghuang and its components as COVID-19 spike protein receptor binding domain inhibitors VI
Part 2. Evaluation of Lung Protection of Sanghuangporus sanghuang through TLR-4/NF-κB/MAPK, Keap-1/Nrf-2/HO-1, CaMKK/AMPK/Sirt-1 and TGF-β/Smad3 Signal Pathways Mediating Apoptosis and Autophagy VIII
Part 3. Study on the protective effects and mechanisms of Sanghuangporus sanghuang on chronic kidney disease X
Part 4. Pharmacological Study of Sanghuangporus sanghuang on Prostate Cancer XI
目錄 XIII
縮寫目錄 XXIII
附圖目錄 XXVI
圖目錄 XXVII
表目錄 XXXII
第一章 緒論 1
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究 1
一、 桑樹桑黃Sanghuangporus sanghuang (SS) 1
二、 Coronavirus Disease-2019 (COVID-19) 3
三、 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 5
四、 Angiotensin-Converting Enzyme 2 (ACE2) 7
五、 Transmembrane Serine Protease 2 (TMPRSS2) 8
六、 Hispidin 9
七、 3,4-Dihydroxybenzalacetone (DBA) 11
八、 Protocatechuic acid (PAC) 13
九、 Protocatechualdehyde (PAD) 15
十、 Caffeic acid (CA) 17
第二、三部分 桑樹桑黃對肺纖維化和慢性腎衰竭之保護作用 19
一、 肺纖維化 19
二、 慢性腎衰竭 20
三、 發炎反應 21
四、 細胞表面受體 22
五、 NF-κB訊號路徑 22
六、 Mitogen-activated protein kinase (MAPKs) 訊號路徑 23
七、 纖維化相關分子 24
八、 CaMKK/AMPK/Sirt-1訊號路徑 24
九、 抗氧化防禦機制 26
十、 Keap-1/Nrf-2/HO-1訊號路徑 27
十一、 細胞凋亡訊號路徑 28
十二、 細胞自噬訊號路徑 28
十三、 腎損傷分子Kidney injury molecule-1 (KIM-1) 29
第四部份 桑樹桑黃對前列腺癌之藥理活性研究 30
一、 前列腺癌 (PCa) 30
二、 Androgen receptor (AR) 31
三、 Sterol Regulatory Element Binding Protein (SREBP) 31
四、 Fatty acid synthase (FASN) 32
五、 Matrix metalloproteinases (MMPs) 和Tissue inhibitors of MMP (TIMPs) 33
第二章 研究動機與目的 34
第一部分 桑樹桑黃及其成分對於COVID-19棘蛋白受體的影響 34
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 35
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究 37
第四部分 桑樹桑黃對前列腺癌之藥理活性研究 38
第三章 研究方法 40
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究實驗架構 40
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 41
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究實驗架構 42
一、 實驗材料 43
二、 細胞培養 45
三、 細胞存活率試驗 47
四、 細胞萃取蛋白 47
五、 西方墨點法 48
六、 動物實驗 48
七、 Glutathione (GSH) 分析 50
八、 Malondialdehyde (MDA) 分析 51
九、 Histopathological stain (H&E stain) 分析 51
十、 Immunohistochemistry (IHC) 分析 52
十一、 統計分析 52
第四部分 桑樹桑黃對前列腺癌之藥理活性研究實驗架構 53
一、 細胞培養 54
二、 細胞存活率試驗 55
三、 傷痕癒合試驗 55
四、 細胞凋亡分析 55
五、 西方墨點法 56
六、 動物實驗 56
第四章 結果與討論 58
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究 58
一、 桑樹桑黃對HepG2和293T細胞生長的影響 58
二、 桑樹桑黃對HepG2和293T細胞中ACE2和TMPRSS2表現的影響 61
三、 酚類化合物對HepG2和293T細胞生長的影響 64
四、 酚類化合物對HepG2和293T細胞中ACE2和TMPRSS2表現的影響 75
五、 小鼠模型中桑樹桑黃的影響 86
六、 Histopathological stain評估實驗小鼠肝及腎毒性 88
七、 Immunohistochemistry染色評估實驗小鼠ACE2和TMPRSS2的表現 90
八、 透過西方墨點法在小鼠模型中評估ACE2和TMPRSS2的表現 97
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 100
一、 桑樹桑黃對Bleomycin誘導的肺纖維化之肺臟指數的影響 100
二、 桑樹桑黃對Bleomycin誘導的肺纖維化中促發炎細胞因子的影響 101
三、 桑樹桑黃對Bleomycin誘導的肺纖維化中氧化壓力變化的影響 103
四、 Histopathological stain評估肺臟損傷的程度 105
五、 Masson Trichrome stain評估Bleomycin誘導的肺纖維化的情況 107
六、 桑樹桑黃對減輕Bleomycin引起肺組織發炎的影響 109
七、 桑樹桑黃對Bleomycin誘導的肺纖維化中TGF-β和Smad3表現的影響 111
八、 桑樹桑黃對Bleomycin誘導的肺纖維化中MAPK信號路徑的影響 113
九、 桑樹桑黃對Bleomycin誘導肺纖維化中fibronectin、collagen和α-SMA表現的影響 115
十、 桑樹桑黃對Bleomycin誘導的肺纖維化中CaMKK/AMPK/Sirt-1信號傳導路徑的影響 117
十一、 桑樹桑黃對Bleomycin誘導的肺纖維化中恢復肺部抗氧化能力和Keap-1/HO-1/Nrf-2信號路徑的影響 119
十二、 桑樹桑黃對Bleomycin誘導的肺纖維化中自噬的影響 121
十三、 桑樹桑黃對Bleomycin誘導肺纖維化中凋亡信號路徑的影響 123
十四、 桑樹桑黃對Bleomycin引起的肺纖維化中MMP2和MMP9的影響 125
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究 127
一、 桑樹桑黃對Cisplatin誘導慢性腎衰竭之腎臟指數和型態的影響 127
二、 桑樹桑黃減少Cisplatin誘導小鼠慢性腎衰竭和組織病理學變化 129
三、 桑樹桑黃對Cisplatin誘導慢性腎衰竭中促發炎細胞因子的影響 131
四、 Masson Trichrome stain評估Cisplatin誘導的慢性腎衰竭程度 133
五、 Periodic acid–Schiff stain評估Cisplatin誘導的慢性腎衰竭程度 135
六、 桑樹桑黃對減輕Cisplatin引起腎組織發炎的影響 137
七、 桑樹桑黃對Cisplatin誘導的慢性腎衰竭中MAPK信號路徑的影響 139
八、 桑樹桑黃對Cisplatin誘導慢性腎衰竭中CaMKK/AMPK/Sirt-1信號傳導路徑的影響 141
九、 桑樹桑黃對Cisplatin誘導慢性腎衰竭中恢復腎臟抗氧化能力和Keap-1/Nrf-2/HO-1信號路徑的影響 143
十、 桑樹桑黃對Cisplatin誘導的慢性腎衰竭中凋亡信號路徑的影響 145
十一、 桑樹桑黃對Cisplatin誘導慢性腎衰竭中fibronectin、collagen和α-SMA表現的影響 147
十二、 桑樹桑黃對Cisplatin誘導的慢性腎衰竭中的KIM-1的影響 149
第四部分 桑樹桑黃對前列腺癌之藥理活性研究 151
一、 桑樹桑黃對PC-3和LNCaP細胞生長的影響 151
二、 桑樹桑黃對PC-3和LNCaP細胞遷移的影響 153
三、 桑樹桑黃PC-3和LNCaP細胞中誘導依賴於caspase的凋亡作用 155
四、 桑樹桑黃抑制PC-3和LNCaP細胞中與AR、脂肪生成和膽固醇生成相關蛋白的表現 157
五、 桑樹桑黃對PC-3和LNCaP細胞中發炎蛋白和下游路徑相關蛋白的影響 159
六、 桑樹桑黃對小鼠皮下PC-3前列腺癌模型的抗腫瘤作用 161
第五章 討論 164
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究 164
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 168
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究 173
第四部分 桑樹桑黃對前列腺癌之藥理活性研究 176
第六章 結論 179
第一部分 桑樹桑黃及其成分作為COVID-19棘蛋白受體結合抑制劑之潛力研究 179
第二部分 桑樹桑黃透過TLR-4/NF-κB/MAPK、Keap-1/Nrf-2/HO-1、CaMKK/AMPK/Sirt-1和TGF-β/Smad3信號路徑誘導細胞凋亡和自噬的肺保護作用 180
第三部分 桑樹桑黃對慢性腎衰竭之保護作用與機轉研究 182
第四部分 桑樹桑黃對前列腺癌之藥理活性研究 184
第七章 引用文獻 185
第八章 著作 225
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