| 摘要: | 桑黃(Phellinus linteus)自古以來即為一種名貴的菇類藥材，同時也為開發保健食品的重要材料之一。民間通常認為桑黃具有抗發炎、保肝、免疫及其他的療效等。目前有關桑黃之SCI 論文發表共有六十幾篇，這些研究報告的焦點集中於液態培養桑黃的生物活性。此外，動物實驗研究亦顯示液態培養桑黃菌絲體所分離之多醣體具有提高免疫及抗癌(肺及黑色素瘤)等功能。但是目前有關固態培養桑黃之體外及體內免疫調節活性與其分子作用機制則不明瞭，因此值得深入研究。本研究主要研究目的，包括：(1) 探討固態培養桑黃萃取物及多醣體對LPS- 誘導的人類單核球(THP-1)細胞對不同基因訊息傳遞途徑如protein kinase C (PKC) 途徑、透過訊息傳遞分子物質包含TLR(-2 及-4)、IRAK(-1 及-4)、骨髓分化因子 (MyD88)及TNF receptor-activated factor 6 (TRAF6)之活化表現、下游細胞核中轉錄因子(NF-κB 及AP-1) 與STAT-1 分子訊息傳遞途徑及化學激素(i.e. MCP-1、 MIP-1β及IL-8)釋放量之影響； (2) 以動物實驗模式探討固態培養桑黃萃取物及多醣體之非特異性免疫(i.e. 細胞吞噬活性、自然殺手細胞活性、細胞激素及抗體量測定、表面抗原分析)與特異性免疫反應(i.e. OVA-誘發特異性抗體產生及OVA- 特異性細胞激素生成)及(3) 進行固態培養桑黃萃取物及多醣體對LPS-誘導的 THP-1 細胞之有絲分裂活性蛋白質激酶(mitogen-activated protein kinases ; MAPKs) 途徑、刺激標誌分子(CD80 及CD86)之表現及對細胞激素之釋放量與免疫調節效應的影響。於2007 年8 月至2008 年7 月，我們已獲得國科會經費補助研究固態培養桑黃之抗癌活性及其作用機制。為進一步研究固態培養桑黃之藥理功能，希望國科會能再繼續提供研究經費，以便有系統的探討固態培養桑黃之體外及體內免疫調節活性及分子作用機制。此研究結果將有助於固態培養桑黃成為高經濟價值保健食品之重要資料依據。
Phellinus linteus, a medicinal fungus, has long been considered as a high value traditional Chinese medicine ingredient and for health food development. It is generally believed to possess anti-inflammatory, hepatoprotective, immunomodulatory and other therapeutic properties. Currently over 60 SCI articles have been reported on P. linteus, of which studies were mainly focused on biological activities of liquid cultured P. linteus. Besides, animal studies also showed that polysaccharide obtained from these liquid cultured P. linteus mycelia possessed immunomodulatory and anti-cancer (lung cancer and melanoma) activities. However, the in vitro and in vivo immunomodulatory properties of solid cultured P. linteus and its immunity signaling pathway and molecular mechanism(s) of action remain unknown. Therefore, it is essential to carry out an insight study in these properties. The aims of this study comprise：(1) to examine the effects of solid cultured P. linteus extracts and polysaccharide on molecular signaling cascades, such as protein kinase C (PKC) system, IL-1 signaling molecules (MyD88, TLR (-2, -4), IRAK(-1, -4), and TRAF6), nuclear signaling molecules (NF-κB, AP-1), STAT-1 and chemokines (MCP-1、MIP-1β及IL-8) secretion in LPS-induced human monocytic cells (THP-1) ； (2) to evaluate the immunomodulatory properties of solid cultured P. linteus extracts and polysaccharide in non-specific (i.e. phagocytosis, natural killer cell activity, CD marker expression, cytokines and antibodies analysis) and specific (i.e. OVA-specific antibodies generation and OVA-specific cytokines release) immuno responses in animals；(3) to investigate the molecular mechanistic effects of solid cultured P. linteus extracts and polysaccharide on immunity signaling, MAPKs pathway, expression of CD markers (CD80, CD86) and cytokines in LPS-induced THP-1 cells. Between 2007 August and 2008 July, we have obtained financial support from the National Science Council (NSC) to examine the anti-cancer properties of P. linteus and its mechanism(s) of action. To continue our research work on P. linteus, we therefore hope that NSC would further provide financial support for our studies on immunomodulatory properties of solid cultured P. linteus in both in vitro and in vivo. Results obtained from this study will provide vital information for the development of solid cultured P. linteus into high economic value health food products. |
