臺灣博碩士論文加值系統

桑黃 (Sanghuangporus sanghuang, sanghuang) 是屬於桑黃屬 (Sanghuangporus) 的藥用真菌，而正宗桑樹桑黃直到 2012 年才經研究被證實為新品種。
截至目前為止，大多數針對桑黃之研究都集中於這兩種品種的桑黃 (S.vaninii, and S. baumii) 是目前被認為功效比較好的桑黃。至今，尚未研究報告證明 S. sanghuang 同於與 S.vaninii 和 S. baumii 具有相同之功效。本研究之目的為針對野生藥用真菌桑樹桑黃 (S. sanghuang) 進行藥理活性之探討，並與現今市場上大量流通之桑黃 (S.vaninii, 和 S. baumii) 做藥理活性比較。然而，現有之研究也尚未探討桑黃子實體 (S. sanghuang) 與其菌絲體之抗發炎之效用。
因此，本研究的目的是評估野生藥用真菌桑黃 (S. sanghuang) 的藥理活性與其他常見的桑黃品種的藥理活性。 另外，我們還利用脂多醣 (LPS) 誘導的體外和體內實驗，探討桑黃子實體和菌絲體對發炎反應的保護作用和可能潛在機制。
我們評估了三種桑黃品種的癌細胞抑制，自由基清除能力和抗炎作用。依據研究結果，我們發現 S. sanghuang，具有豐富的多酚類化合物，具有抗氧化，抗發炎和抗腫瘤細胞增生之能力，更優於其他兩種品種之桑黃。
在桑樹桑黃子實體部分，依據結果發現當給予桑黃之組別，可顯著減弱因 LPS 誘發之肺水腫，支氣管肺泡灌洗液中 interleukin (IL)-1β, tumor necrosis factor (TNF)-α 和 IL-6 之濃度，且能顯著改善小鼠之肺組織損傷。此外，桑黃對 LPS 誘導之 ALI 具抗發炎之效用，推測可能是藉由於抑制 TLR4 所調控的 PI3K/AKT/mTOR/IKKβ Signaling Pathway 和 NF-κB、MAPK pathways 之能力。然而，在本研究結果表中，我們發現桑黃通過調控 NF-E2相關因子 2 (Nrf2) 蛋白質的表現量，進而影響肺組織中 HO-1、thioredoxin-1 (Trx-1) 等抗氧化酵素之生成，改善因LPS 誘導的所生成之 ROS 帶來之氧化壓力。
此外，桑樹桑黃菌絲體的使用也可以抑制 LPS 誘導的炎症反應，期透過減少炎症細胞數，抑制骨髓過氧化酵素之活性，調控 TLR4 / PI3K/Akt / mTOR/ NF-κB 和 MAPK pathway，並抑制高遷移率族蛋白B1 之活性。另外，桑黃菌絲體能影響肺組織中抗氧化酵素及 HO-1 和 Trx-1 之合成，並藉由調控 KRAB-associated protein-1 (KAP1)/ nuclear factor erythroid-2-related factor (Nrf2)/ Kelch Like ECH associated Protein 1 (Keap1) pathway。
因此，基於所有實驗結果，我們認為 S. sanghuang 子實體與其菌絲體對小鼠 LPS 誘導的 ALI 具有保護作用。 S. sanghuang 子實體和菌絲體可用於治療或預防炎症相關疾病。這項研究的結果可提供往後使用桑黃作為膳食補充劑或治療之效用之參考。

Sanghuangporus sanghuang (S. sanghuang) is a mushroom that belongs to the genus Sanghuangporus and it is commonly called “Sangwhang” in China andTaiwan. It is popular in oriental countries and has been traditionally used as food and medicine. The mystery surrounding it was solved in 2012, when it was discovered. S. sanghuang is a rare fungal species that grows on wild mulberry trees, and its yield is much lower than that of valuable medicinal herbs such as saffron and other fungal species such as Cordyceps sinensis and Antrodia cinnamomea.
The annual production of Sanghuangporus vaninii (S. vaninii) is approximately 40 tons. Sanghuangporus baumii (S. baumii) is widely distributed and commonly used. Most studies so far have focused on Tropicoporus linteus (T. linteus). These three Sanghuang varieties (T. linteus, S. vaninii, S. baumii) are currently considered as having the best pharmacological efficacy. Until now, no reports have demonstrated that S sanghuang has the same efficacy as that of T. linteus and S. baumii. However, the existing research has not yet studied extensively the anti-inflammatory effects of sanghuang fruiting bodies that grows on Morus trees or sanghuang mycelium.
Therefore, the objective of this study was to analyze the pharmacological activity of the wild medicinal fungus S. sanghuang (on Morus) in comparison with that of other commonly available Sanghuang varieties. In addition, we also explore the protective effects and underlying mechanism of sanghuang fruiting bodies and mycelium on inflammation by lipopolysaccharide (LPS) induced In vitro and In vivo.
We evaluated the cancer cell inhibition, free radical scavenging ability, and anti-inflammatory effects of the three Sanghuang varieties. The results showed S. sanghuang to be the most efficacious Sanghuang basidiocarp of the two varieties, rich in polyphenolic compounds, having antioxidant, anti-inflammatory, and tumor suppressive ability.
In the part of the sanghuang fruiting bodies, results showed that sanghuang treatment markedly attenuated LPS-induced lung edema, elevation of the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in bronchoalveolar lavage fluid (BALF) accompanied by a remarkable improvement of lung histopathological symptoms. Additionally, western blotting results suggest that anti-inflammatory effects of sanghuang against the LPS-induced ALI may be due to its ability of inhibition of the TLR4-Mediated PI3K/AKT/mTOR/IKKβ Signaling Pathway and NF-κB 、MAPK signaling pathways. Notably, our results suggest that sanghuang suppresses LPS-induced ROS by inducing Nrf2 activation and HO-1、thioredoxin-1 expression in the lung tissues.
In addition, the experimental results showed that the administration of mycelium of S. sanghuang could inhibit LPS-induced inflammation. Mycelium of S. sanghuang could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, mycelium of S. sanghuang could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/ nuclear factor erythroid-2-related factor (Nrf2)/ Kelch like ECH associated Protein 1 (Keap1) pathway.
Therefore, based on all experimental results, we propose that S. sanghuang fruiting bodies and mycelium of S. sanghuang exhibits a protective effect against LPS-induced ALI in mice. The fruiting bodies and mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases. Results of this study provide a basis for future use of these Sanghuang species as dietary supplements or therapeutic agents.

目錄
學位考試委員審定書 i
本校論文電子檔案上網授權書 ii
中國醫藥大學研究生無違反學術倫理聲明書 iii
謝辭 iv
目錄 v
表目錄 viii
圖目錄 ix
中文摘要 xiii
英文摘要 xvi
第一章 緒論 1
第一節 桑黃 1
第二節 發炎反應與氧化壓力 10
第三節 急性肺損傷 20
第二章 研究緣起 25
第一節 研究動機 25
第二節 研究目的 28
第三章 不同種類桑黃之乙醇提取物其抗氧化，抗發炎和抗腫瘤細胞增殖活性之評估 29
第一節 前言 29
第二節 材料方法 33
第三節 結果 41
第四節 討論 46
第五節 小結 50
第四章 桑樹桑黃 (Sanghuangporus sanghuang) 子實體 之抗發炎活性與抑制 TLR4/PI3K/AKT/mTOR/IKKβ 訊息傳導路徑之關係 58
第一節 前言 58
第二節 材料與方法 62
第三節 結果 78
第四節 討論 85
第五節 小結 94
第五章 桑黃菌絲體抗發炎活性之評估 108
第一節 前言 108
第二節 材料與方法 112
第三節 結果 117
第四節 討論 123
第五節 小結 129
第六章 結論 139
參考文獻 141
附錄 研究成果投稿於國外學術期刊之摘要 166

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