臺灣博碩士論文加值系統

第二型糖尿病是全世界常見代謝和內分泌紊亂的慢性病，導致嚴重的健康和經濟問題，由文獻探討糖尿病防治之天然物包含有自由基清除劑、抗氧化物及多醣體等。因此本論文分析16種市售蕈菇之水和酒精萃取物，除分析類三萜、固醇類、生物鹼、及還原糖基，並選擇具抗氧化成分之gallic acid和trolox作為正對照組，進行DPPH自由基清除能力、ABTS‧+自由基清除能力、總多酚含量、總多醣含量測定32種酒及水萃取物(EE及WE)，結果顯示，DPPH自由基清除能力依序為洋菇(EE)、黑木耳(EE)、靈芝成熟子實體(FB)(WE)、雲耳(EE)、茶樹菇(EE)，其半抑制濃度(IC50)分別為279.5、281.5、308.5、332.8及437.8 μg/ml； gallic acid與trolox分別為5.7及8.2 μg/ml。清除ABTS‧+自由基能力依序為靈芝FB(EE)、茶樹菇(EE)、靈芝幼蕾子實體(BD) (WE)、黑木耳(WE)、靈芝FB (WE)，其半抑制濃度(IC50)分別為213.3、240.9、254.5、261.7、及282.5 μg/ml；gallic acid、trolox分別為4.6及8.5 μg/ml。另外，32種萃取物的總多酚量為相當gallic acid 相當量(GAE) :0.677~ 0.157 μg/mg extracts。總多醣定量以glucose之相當量(GE) μg，依序為茶樹菇(EE)、杏鮑菇(WE)、猴頭菇(EE)、香菇-ES(EE)、香菇-LF(EE)，當量分別為594.64、554.25、522.1、504.21及459.38 μg GE/mg extracts。綜合以上之結果，茶樹菇(EE)萃取物不但含豐富多醣，同時具有顯著抗氧化能力；另，茶樹菇多醣已被研究證實具有抑制NO和COX-2可被應用於如炎症和癌症之治療。此外，茶樹菇多醣也被發現有顯著抑制STZ誘導的糖尿病小鼠iNOS的表達和血糖水平以及在免疫組織化學分析上顯示有增強了胰臟β細胞對STZ破壞的抗性。因此，茶樹菇無論是在糖尿病營養補充品或新藥之研究上均具有開發之潛力。

Type 2 diabetes is a world wild and metabolic, endocrine disorder related chronic disease, causing a series severe complications and economics issue. According to past studies, the nutrition supplements of natural anti-diabetes compounds including free radical scavenger, antioxidants and polysaccharides. Therefore, the phytochemicals analyzed triterpenes, steroids, alkaloids and reducing sugar function group of 16 commercially mushroom from Taiwan. In this study, gallic acid and trolox were positive control agents. The efficacies of DPPH free redical scavenging activity, ABTS‧+ anti-oxidation capacity, total phenolics and total polysaccharide contents of each ethanol extract (EE) and water extract (WE) were measured. Results showed(1) the best five potential DPPH- radical scavenging extracts are Agaricus bisporus (AB-EE)、Auricularia auricular (AA-EE)、Gonoderma lucidum (FB) (GFB-WE)、A. auricula-judae (EE)、and Agrocybe chaxingu (AC-EE), and IC50 were 279.5、281.5、308.5、332.8、437.8 μg/ml, respectively; gallic acid and trolox were 5.7 and 8.2 μg/ml.
(2) The anti-oxidation (ABTS‧+) potential extracts are Gonoderma lucidum (FB) (GFB-EE)、AC-EE、GBD-WE、Agrocybe chaxingu (WE)、GFB-WE, IC50 are 213.3、240.9、254.5、261.7 and 282.5 μg/ml, respectirely.(3) The total phenolics of extracts were 0.677 ~ 0.157 GAE µg/g. (gallic acid equivalent scavenging activity，GAE) (4) The high total polysaccharide contenting extracts are AC-EE、Pleurotus eryngiig (WE)、Hericium erinaceus(EE)、Lentinula edodes-ES(EE)、L. edodes-LF(EE)594.64, 554.25, 522.1, 504.21 and 459.38 GE ug/g (glucose equivalent, GE), respectively.
In view the above results, the highest polysaccharide containing extract is AC-EE, it also has antioxidant efficacy. Many studies had been improved the polysaccharides of Agrocybe chaxingu have biological activities of NO, COX-2 inhibitions. Otherwise, it also significantly inhibited iNOS expression and blood glucose levels in streptozocin(STZ)-induced diabetic mice. Moreover, immunohistochemical analysis revealed that it enhanced pancreatic beta-cells resistance to destruction by STZ. The conclusion exhibited the Agrocybe chaxingu will be a potential to develop the nutrition supplement or new drug for the related disease including inflammation, cancer and anti-diabetes.

目錄
摘要 I
ABSTRACT II
誌謝 III
目錄 IV
圖目錄 VII
表目錄 VIII
第一章 緒論 1
第一節 研究動機 4
第二節 研究目的 5
第一節 研究流程 6
第二章 文獻回顧與探討 7
第一節 蕈菇簡介 7
一、生物分類 7
二、傳統應用 7
三、健康營養價值 8
四、栽培 9
五、藥理作用 11
六、生物活性成分 19
七、香菇常用之段木樹材 22
第二節 天然多醣對糖尿病的改善能力 25
一、醣類 25
二、多醣對糖尿病的改善能力 26
三、多醣的免疫調節能力 28
第三節 糖尿病簡介 29
一、糖尿病定義與分類 29
二、糖尿病對生理健康的影響 30
三、胰島素抗性 31
四、糖尿病和抗氧化 31
五、天然胰島素分泌促進之天然資源 33
第三章 實驗材料與方法 38
第一節 文獻探詢方法 38
第二節 實驗材料 39
一、蕈菇材料 39
二、化學試藥 41
三、實驗儀器與設備 42
第三節 實驗方法 43
一、實驗材料萃取製備 43
二、檢測品製備 43
三、植物化學素定性分析 44
四、生物活性定量與總多醣含量測定方法 47
1. 清除1,1-Diphenyl-2-picrylhydrazlhydrate（DPPH）自由基能力試驗 48
2. 清除ABTS‧+ [2,2-Azino-bis-（3-ethylbenzothiazoline-6-sulfonate acid）]陽離子試驗 50
3. 總多酚化合物含量測定 51
4. 總多醣化合物含量測定 52
第四章 實驗結果 54
第一節 16種蕈菇萃取物之產率 54
第二節 植物化學素定性分析結果 55
第三節 抗氧化、自由基清除能力測定結果 57
第四節 總多酚定量測定結果 70
第五節 總多醣定量測定結果 73
第五章 討論 76
第一節 蕈菇中之植化素 76
第二節 16種蕈菇萃取物之抗氧化力生物活性結果與糖尿病之應用 80
第三節 香菇栽培之不同寄主對生物活性影響 81
第四節 不同採收時段靈芝對生物活性影響 82
第五節 黑木耳、杏鮑菇、茶樹菇之生物活性 83
第六章 結論與建議 84
文獻參考 86
中文文獻 86
英文文獻 91
附錄 105
圖目錄
圖1 研究方法流程圖 6
圖2 蕈菇栽培流程圖 10
圖3 Triterpenoid之化學結構式 20
圖4 不同段木栽培之香菇 40
圖5 不同採收階段之靈芝 40
圖6 植化素合成途徑 44
圖7 DPPH自由基清除反應式 48
圖8 ABTS‧+自由基清除反應式 50
圖9 萃取產率 55
圖10 Gallic acid標準品DPPH自由基清除率檢量線 58
圖11 Trolox標準品DPPH自由基清除率檢量線 58
圖12 Gallic acid標準品ABTS‧+自由基清除率檢量線 58
圖13 Trolox標準品ABTS‧+自由基清除率檢量線 58
圖14 16種蕈菇水萃取物DPPH自由基清除率 61
圖15 16種蕈菇水萃取物ABTS‧+自由基清除率 61
圖16 16種蕈菇酒精萃取物DPPH自由基清除率 63
圖17 16種蕈菇酒精萃取物ABTS‧+自由基清除率 63
圖18 16種蕈菇萃取物之DPPH自由基清除能力IC50柱狀圖 64
圖19 16種蕈菇萃取物之ABTS‧+自由基清除能力IC50柱狀圖 67
圖20 Gallic acid標準品總多酚檢量線 70
圖21 16種蕈菇水萃取物的總多酚含量 72
圖22 16種蕈菇酒精萃取萃物的總酚含量 72
圖23 Glucose標準品總多醣檢量線 73
圖24 16種蕈菇水萃取物總多醣含量 75
圖25 16種蕈菇酒精萃取物總多醣含量 75
表目錄
表1 蕈菇栽培方法 9
表2 蕈菇天然多醣對糖尿病的作用 27
表3 實驗蕈菇材料表 39
表4 16種蕈菇萃取物與乾燥材料換算表 54
表5 16種蕈菇水萃取物植物化學素定性分析 56
表6 16種蕈菇酒精萃取物植物化學素定性分析 57
表7 16種蕈菇水萃取物自由基清除率 60
表8 16種蕈菇酒精萃取物自由基清除率 62
表9 16種蕈菇萃取物的總多酚含量 71
表10 16種蕈菇萃取物的總多醣含量 74
表11 16種蕈菇水萃及酒精萃取物含生物鹼之測試 79
表12 不同生長階段靈芝生物活性 82
表13 黑木耳、杏鮑菇、茶樹菇之生物活性 83

中文文獻
行政院衛生福利部統計處(2017). 105年死因統計結果分析。
行政院衛生福利部統計處(2017). 105年縣市別糖尿病死亡概況統計。
行政院衛生福利部國民健康署(2007–2012)歷年糖尿病盛行率。
行政院衛生福利部國民中央健康保險署醫療費用支出(2015). 2014年前十名。
行政院衛生福利部國民健康署(2015). 國際糖尿病聯盟世界糖尿病大會出國報告
行政院衛生福利部國民健康署(2014). 糖尿病防治手冊(糖尿病預防、診斷與控制流程指引) 。
行政院衛生福利部國民健康署 (2007). 年台灣地區高血壓、高血糖、高血脂之追蹤調查研究專輯。
中華民國糖尿病衛教學會 (2012，8月).《認識糖尿病》。
食品發展工業研究所，《植物多酚類的機能性與安全性》，0089120049。
TrendForce (2016). 2015–2030全球糖尿病患人口數與相關醫療支出金額預估。
丁仁鳳、何普明、揭國良 (2005). Study on the Hypoglycemic Mechanism of Tea Polysaccharides and Tea Polyphenols.《茶葉科學》，25(3)：219-224。
丁懷謙 (2000). 食藥用菇多醣體之免疫生理活性，《食品工業》，32(5)，28-42。
水野 卓、川合正允 (賴慶亮譯) (1996). 菇類的生化學，台北：國立編譯館。
尹紅力，趙鑫，佟麗麗，王振宇 (2015). 黑木耳多糖體外和體內降血糖功能，《食品科學》，36(21): 221-227。
方怡丹、蔡清榮 (2016). 臺灣菇類產業之發展與輔導，《菇類生技產業研討會專刊》，29(34)：29-34。
王伯徹 (2005). 具開發潛力食藥用菇介紹，《食藥用菇菌類保健食品產業發展彙編（上）》。新竹：食品工業發展研究所，103-132。
王伯徹、陳啟楨、華傑 (1998) 《食藥用菇類的培養與應用》，財團法人食品工業發展研究所報告，M87-019，187。
王建軍 、宋成武、 柳冬月、 蕭菲菲、 余尚工 、方念伯 (2011). 複方香菇提取物對糖尿病模型小鼠的實驗研究，Journal of Hubei University of Chinese Medicime，13(4)，3-5。
王賽時 (2007). 略論中國古代食用菌的開發與食用，Journal of Chinese Dietary Culture，3(2)：73-104。
石信德 (2010). 食藥用菇類液體菌種栽培技術之潛力，《農業生技產業季刊》，23，16-21。
呂昆霖 (2006). 綠藻之Beta -1,3 -葡萄聚醣在化妝品上的應用，嘉南藥理科技大學專題研究計畫成果報告，1-3。
呂昀陞、陳美杏、李瑋崧、吳寬澤、簡宣裕(2011). 菇類栽培後介質之再利用，《菇類產業發展研討會專刊》，59-70。
李維欽 (2001). 食用油脂、抗氧化劑與健康食品萃取物在 C57BL / 6 小鼠血漿脂質及肝臟抗氧化酵素脂影響，陽明大學生物化學研究所碩士論文。
李建瑩、施宏哲、蔡敏鈴、羅美婷(2009).治療第二型糖尿病藥物簡介， The Journal of Taiwan Pharmacy《藥學雜誌》，98 18-26。
李新進. 實驗室各種溶液與試劑之配製，農委會家畜衛生試驗所<http://vettech.nvri.gov.tw/Articles/handbook/65.html>。
沈宜靜、林建良、許惠恒 (2011). 糖尿病與癌症之關聯以及台灣現況探討，《內科學誌》22：19-30。
周碧瑟、董道興、李佳琳、莊紹源、林敬恆、楊南屏(2002). 台灣地區糖尿病流行病學，台灣公共衛生雜誌，21(2)：83-96。
林貴福、盧淑雲 (2011). 《運動保健與體適能》，台北：冠學 12。
林榮耀 (1996). 靈芝及菇類等真菌類免疫調節蛋白質之研究及探討其臨床應用性，《生命科學簡訊》，10：2-5。
翁啟惠口述 吳亭瑤採訪整理 (2005).中研院士翁啟惠對靈芝多醣的觀點，《健康靈芝》，27，8-13。
翁瑞亨、徐瑞祥、謝玉娟 (2002). 台灣地區糖尿病共同照護現況，《台灣醫界》6(4)，569-573。
張力詳 (2017). 臺灣綠化樹木醣類含量年變化研究—以樟樹和楓香為例，中興大學園藝學系所論文；1 - 85。
張海嵐、周建平、邊洪榮 (2004). 香菇有效成分研究綜述，J North China Coal Medical College January，6(1)，35。
張鈞涵、李汶軒、時雨青、黃豆己惟、張上鎮、廖秀娟 (2016). 以秀麗隱桿線蟲為模式生物探討相思樹嫩枝萃取物之生物體內抗氧化，《中華林學季刊》，(4):503-514。
馬迪、馮娜、馮愛萍、韓偉、譚琦 (2016). 不同生長期草菇提取物的生物活性研究，《菌物學報》，35(10)：1226-1233。
馬養民、馮成亮 (2009). 植物內生真菌生物鹼活性成分的研究進展，《有機化學》，29(8)，1182-1191。
郭怡伶 (2008). 第2型糖尿病患飲食攝取和血糖控制之關係，中山醫學大學營養學研究所論文，20-46。
陳水田 (2006). 從解構靈芝多醣到探討靈芝的雙向調節作用，《健康靈芝》，34，30-33。
陳金柱、李思遠、郭宗正 (2006). 胰島素阻抗之病理生理學，《台灣醫界》，49(9)，28-34。
陳宗明 (2016). 台灣菇類產業發展現況，《菇類產業發展研討會專刊》，25-31。
陳裕鏞、張鴻民 (2004）.《科學發展》，384，30-37。
陳美杏、呂昀陞、李瑋崧、石信德、吳寬澤 ( 2011). 台灣菇類育種現況與展望，《菇類產業發展研討會專刊》，79-92。
陳良宇、鄭建瑋、王志玄、林志璋、張云力、李瑞玲、游欣、梁致遠 (2012). 鹼催化對Folin-Ciocalteu試劑檢測總多酚含量的影響。MC-Transaction on Biotechnology, 4，10-19。
陳惠英、 顏國欽 (1998). 自由基、抗氧化防禦與人體健康，《臺灣營養學會雜誌》23(1)，105 –121。
曾慶孝 (2006). 老化與糖尿病，台灣大學校友雙月刊，43期。<http://www.alum.ntu.edu.tw/wordpress/?p=1141>
黃人珍、趙莉芬等編著 (2010). 內分泌與代謝障礙病人的護理《最新實用內外科護理學》四版，台北：永大83-129。
黃仁彰 (2000). 菇類多醣體製劑的研發與應用，《食品工業》，32(10)，45-58。
楊懿珊 (2012). 菇蕈類多醣體多元化市場應用，《食品工業》，44(5)，40-57。
劉育姍，康瑋帆，呂昀陞，石信德 (2016). 我國菇類產業現況與技術發展策略分析，行政院農業委員會農政與農情，285，72-82。
劉立偉 (2008). 咸豐草與楓香之抗氧化性及成分分析，大葉大學生物產業科技學系論文，1-90。
樊一橋，武謙虎，盛健惠 (2009). 黑木耳多糖抗血栓作用的研究，《中國生化藥物雜誌》，30(6)，410- 412。
蔡崇煌、陳靖棻、蔡新聲、黃青真 (2010). 苦瓜於血糖控制之功效及安全性回顧，《臺灣營養學會雜誌》，35(3)：115-126
鄭啟源 (2012). 林新醫院內科衛教，《認識糖尿病藥物以維持良好血糖控制》<http://www.lshosp.com.tw/wei/Folder/Internal_Medicine/IM_029_001.htm>
黎孝韻、曾國慶 (2008). 自由基及抗氧化物功能的探討， The journal of Taiwan pharmacy，《藥學雜誌》，95，95-103。
顏幸達 (1996). 楓香之本草考察及其果實路路通之鎮痛藥理研究，中國醫藥學院中國要學研究所論文，1-50。
顏銘宏 (1999). 簡介有毒植物的毒性成分及毒理作用，《高醫醫訊月刊》，18(10)。
蕭浚宏 (2011). 楓香滲出物成分解析及其生物活性探討，中興大學森林學系論文，1 - 136。
蕭淑華、吳達仁 (2014). Metformin治療第2型糖尿病患限制的探討，《內科學誌》，25，1-6。
蘇慶華 (2006).《健康靈芝》，32，42-44。
英文文獻
Abdulla MA, Fard AA, Sabaratnam V, Wong KH, Kuppusamy UR, Abdullah N, Ismail S. (2011). Potential activity of aqueous extract of culinary-medicinal Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating wound healing in rats. Int J Med Mushrooms. 13(1):33-9.
Agwaya MS, Vuzi PC, Nandutu AM. (2016). Hypoglycemic Activity of Aqueous Root Bark Extract Zanthoxylum chalybeum in Alloxan-Induced Diabetic Rats. J Diabetes Res. 2016:8727590.
Alicia GR, Caz V, Smiderle FR, Roberto MH, Largo C, Tabernero M, Marín FR, Iacomini M, Reglero G, Rivas CS. (2016). Water-Soluble Compounds from Lentinula edodes Influencing the HMG-CoA Reductase Activity and the Expression of Genes Involved in the Cholesterol Metabolism. J. agric. Food Chem., 64(9), 1910-1920
Appiah T, Boakye YD, Agyare C. (2017). Antimicrobial activities and time-kill kinetics of extracts of selected Ghanaian mushroom. Evid Based complement Alternat Med. 2017:4534350
Aruoma OI. (1999). Antioxidant actions of plant foods: use of oxidative DNA damage as a tool for studying antioxidant efficacy. Free Radic Res. 1999;30:419-427.
Ashraf R, Khan RA, Ashraf I. (2011). Garlic (Allium sativum) supplementation with standard antidiabetic agent provides better diabetic control in type 2 diabetes patients. Pak J Pharm Sci. 24(4):565-70.
Bae S, Kang SC, Song YJ. (2017). Inhibition of human cytomegalovirus immediate- early gene expression and replication by the ethyl acetate (EtOAc) fraction of Elaeocarpus sylvestris in vitro. BMC Complement Altern Med. 29;17(1):428
Bai Y, Zang XL, Ma JS, Xu GG. (2016). Anti-Diabetic Effect of Portulaca oleracea L. Polysaccharideandits Mechanism in Diabetic Rats. Int J Mol Sci. 17(8): 1201.
Basch E, Gabardi S, Ulbricht C. (2003). Bitter melon (Momordica charantia): a review of efficacy and safety. Am J Health Syst Pharm. 60(4):356-9.
Bahar E, Akter KM, Lee GH, Lee HY, Rashid HO, Choi MK, Bhattarai KR, Hossain MM, Ara J, Mazumder K, Raihan O, Chae HJ, Yoon H. (2017). β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS). BMC Complement Altern Med. 17(1):179.
Baby S, John AJ, Govindan B. (2015). Secondary metabolites form Ganoderma. Phytochemistry. 114: 66-101.
Bohn JA, BeMiller JN. (1995). (1→3)-β-d-Glucans as biological response modifiers: a review of structure-functional activity relationships. 28(1): 3-11
Brglez Mojzer E, Knez Hrnčič M, Škerget M, Knez Ž, Bren U (2016). Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects. Molecules. 11;21(7).
Buchanan MS, Carroll AR, Pass D, Quinn RJ. (2007). NMR spectral assignments of a new chlorotryptamine alkaloid and its analogues from Acacia confusa. Magn Reson Chem. 45(4):359-61.
Cai L, Li R, Tang WJ, Meng G, Hu XY, Wu TN. (2015). Antidepressantlike effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis. Eur Neuropsychopharmacol. 25(8), 1332-41.
Cai M, Lin Y, Luo YL, Liang HH, Sun PL. (2015). Extraction, Antimicrobial, and Antioxidant Activities of Crude Polysaccharides from the Wood Ear Medicinal Mushroom Auricularia auricula-judae (Higher Basidiomycetes). Int J Med Mushrooms. 17(6):591-600.
Chang ST and Miles PG. (1991). Recent Trends in World Production of Cultivated Edible Mushrooms. Mushroom Journal. 504, 15-18.
Chang ST, Wu JH, Wang SY, Kang PL, Yang NS, Shyur LF. (2001) Antioxidant activity of extracts from Acacia confusa bark and heartwood. J Agric Food Chem. 49:3420–3424.
Calderon-Montaño JM, Burgos-Moron E, Perez-Guerrero C, Lopez-Lazaro M. (2011). A review on the dietary flavonoid kaempferol. Mini Rev Med Chem. 11(4): 298–344.
Chang ST, Wasser SP. (2012). The role of culinary-medicinal mushrooms on human welfare with a pyramid model for human health. Int J Med Mushrooms. 14(2):95-134
Chen GT, Fu YX, Yang WJ, Hu QH, Zhao LY. (2017). Effects of polysaccharides from the base of Flammulina Velutipes stipe on growth of murine RAW264.7, B16F10 and L929 cells. Int J Biol Macromol. 107(Pt B):2150-2156.
Chen J, Zeng X, Yang YL , Xing YM , Zhang Q, Li JM , Ma K , Liu HW ,Guo SX.(2017) .Genomic and transcriptomic analyses reveal differential regulation of diverse terpenoid and polyketides secondary metabolites in Hericium erinaceus. Scientific Reports. 7: 10151.
Chien SC, Young PH, Hsu YJ, Chen CH, Tien YJ, Shiu SY, Li TH, Yang CW, Marimuthu P, Tsai LF, Yang WC. (2009). Anti-diabetic properties of three common Bidens pilosa variants in Taiwan. Phytochemistry. 70(10):1246-54.
Chang CJ, Lin CS, Lu CC, Martel J, KO YF, Ojcius DM, Tseng SF, WU TR, Chen YM, Young JD, Lai HC. (2017). Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun. 8:16130.
Day C, Cartwright T, Provost J, Bailey CJ. (1990). Hypoglycaemic effect of Momordica charantia extracts. Planta Med. 56(5):426-9.
Daglia M, Di Lorenzo A, Nabavi SF, Talas ZS, Nabavi SM. (2014). Polyphenols: well beyond the antioxidant capacity: gallic acid and related compounds as neuroprotective agents. Curr Pharm Biotechnol. 15(4):362-72.
Dehghan H, Sarrafi Y, Salehi P (2016). Antioxidant and Antidiabetic Activities of 11 Herbal Plants from Hyrcania Region, Iran. J Food Drug Anal. 179-188.
Ding RF, HE PM, JIE GL. (2005). Study on the Hypoglycemic Mechanism of Tea Polysaccharides and Tea Polyphenols. Journal of Tea Science. 2005-03.
Diao YL, Jiang W, Zhu T, Meng DL, Shan JJ. (2011). Antidiabetic activitiesof natural plant polysaccharides and their advances. Journal of International Pharmaceutical Research. 38(4): 275-279.
Domínguez Avila JA, Rodrigo García J, González Aguilar GA, de la Rosa LA (2017). The Antidiabetic Mechanisms of Polyphenols Related to Increased Glucagon-Like Peptide-1 (GLP1) and Insulin Signaling. Molecules. 30: 22(6).
Duthie GG, Brown KM. (1994). Reducing the risk of cardiovascular disease. In: Goldberg I, editor. Functional Foods. Chapman & Hall. pp. 19-38.
Dubois M, Gilles KA, Hamilton JK, Rebers PA and Smith F. (1956). Colorimetric method for determination of sugars and related substances. Anal Chem. 28(3): 350-356.
Eidi A, Eidi M, Esmaeili E. (2006). Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine. 13, (9–10), 624-629.
El-Sayed MI. (2011). Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy. J Ethnopharmacol. 137(1):643-51.
Ferreira SS, Passos CP, Madureira P, Vilanova M, Coimbra MA. (2015). Structure -function relationships of immunostimulatory polysaccharides: A review. Carbohydr Polym. 132: 378-96.
Ganeshpurkar A, Kohli S, Rai G. (2001). Antidiabetic Potential of Polysaccharides from the White Oyster Culinary-Medicinal Mushroom Pleurotus florida (Higher Basidiomycetes). Int J Med Mushrooms. 16(3):207-17.
Gao Y, Zhou S, Jiang W, Huang M, Dai X. (2003). Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 32(3):201-15.
Gouveia S, Figueira PC. (2011). Antioxidant potential of Artemisia argentea L'Hér alcoholic extract and its relation with the phenolic composition. Food Res Int. 44: 1620-1631.
Heleno SA, Martins A, Queiroz MJ, Ferreira IC.(2015). Bioactivity of phenolic acids: metabolites versus parent compounds: a review. Food Chem. 173:501-13.
Homer JA, Sperry J. (2017). Mushroom-Derived indole alkaloid. J. Nat. Prod.80(7), 2178-2187.
Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P. (2007). The mushroom Agaricus blazei murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo -controlled clinical trial. J Altern Complement Med. 13(1):97-102.
Huie CW, Di X. (2004). Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components. J Chromatogr B. 812:241-257.
Hsu YJ, Lee TH, Chang CL, Huang YT, Yang WC. (2009) Anti-hyperglycemic effects and mechanism of Bidens pilosa water extract. J Ethnopharmacol. 122(2):379-83.
International Diabetes Federation (2015). IDF diabetes atlas 7th edition
Jia X, Yang J, Wang Z, Liu R, Xie R. (2014). Polysaccharides from Laminaria japonica show hypoglycemic and hypolipidemic activities in mice with experimentally induced diabetes. Exp Biol Med . 239(12): 1663-70.
Jayasuriya WJ, Wanigatunge CA, Fernando GH, Abeytunga DT, Suresh TS. (2015) Hypoglycaemic activity of culinary Pleurotus ostreatus and P. cystidiosus mushrooms in healthy volunteers and type 2 diabetic patients on diet control and the possible mechanisms of action. Phytother Res. 29(2):303-9.
Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, Cho KY, Song CH. (2010). White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutr Res. 30(1):49-56.
Kaur C, Kapoor HC. (2002). Anti-oxidant activity and total phenolic content of some Asian vegetables. Int J Food Sci Technol. 37 (2002) 153–161.
Kiho T, Sobue S, Ukai S. (1994). Structural features and hypoglycemic activities of two polysaccharides from a hot-water extract of Agrocybe cylindracea. Carbohydr Res. 251:81-7.
Kimura Y, Kido T, Takaku T, Sumiyoshi M, Baba K. (2004). Isolation of an anti -angiogenic substance from Agaricus blazei Murill: Its antitumor and antimetastatic actions. Cancer Sci. 95(9):758-64.
King P, Peacock I, Donnelly R. (2001). The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 48(5): 643-648.
Kirk PM, Cannon PF, Minter DW, Stalpers JA. (2008). Ainsworth & Bisby's Dictionary of the Fungi. 10th edn. CABI, UK.
Kirkman MS, Briscoe VJ, Clark N, et al. (2012). Diabetes in older adults: a consensus report. J Am Geriatr Soc. 60:2342–2356.
Kitts DD. (1997). An evaluation of the multiple effects of the antioxidant vitamins. Trends Food Sci Technol. 8(6):198-203.
Kogan G. (2000). 1→3,1→6-β-D-Glucan of yeasts and fungi and their biological activity. Studies in Natural Products Chemistry. 23:107-152.
Lachowicz S, Oszmiański J, Seliga Ł, Pluta S. (2017). Phytochemical Composition and antioxidant Capacity of Seven Saskatoon Berry (Amelanchier alnifolia Nutt.) Genotypes Grown in Poland. Molecules. 22(5).
Lee BR, Lee YP, Kim DW, Song HY, Yoo KY et al., (2010). Amelioration of streptozotocin -induced diabetes by Agrocybe chaxingu polysaccharide. Mol Cells. 29(4):349-54.
Li JM, Shah AM. (2003). ROS Generation by Nonphagocytic NADPH Oxidase: Potential Relevance in Diabetic Nephropathy. J Am Soc Nephrol. 14: 221-226.
Li XD, Yu ZQ, Long SH, Guo YL, Duan DL. (2012). Hypoglycemic Effect of Laminaria japonica Polysaccharide in a Type 2 Diabetes Mellitus Mouse Model. ISRN Endocrinol. 507462.
Lin L, Cui F, Zhang J, Gao X, Zhou M, Xu N, Zhao H, Liu M, Zhang C, Jia L. (2016) Antioxidative and renoprotective effects of residue polysaccharides from Flammulina velutipes. Carbohydr Polym. 146:388-95
Lin SB, Li CH, Lee SS, Kan LS. (2003) Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci. 72(21):2381-90.
Li JP, Lei YL, Zhan H. (2014). The effects of the king oyster mushroom Pleurotus eryngii (higher Basidiomycetes) on glycemic control in alloxan-induced diabetic mice. Int J Med Mushrooms. 16(3):219-25.
Liang B, Guo Z, Xie F, Zhao A. Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats. BMC Complement Altern Med. 13:253.
Li J, Zhang B, Liu H, Zhang X, Shang X, Zhao C. (2016). Triterpenoids from Ainsliaea yunnanensis Franch. and Their Biological Activities. Molecules. 21(11).
Li S, Li J, Zhang J, Wang W, Wang X, Jing H, Ren Z, Gao Z, Song X, Gong Z, Jia L. (2017). The Antioxidative, Antiaging, and Hepatoprotective Effects of Alkali- Extractable Polysaccharides by Agaricus bisporus. Evid Based Complement Alternat Med. 2017:7298683.
Lindequist U, Niedermeyer TH, Jülich WD (2005). The Pharmacological Potential of Mushrooms. Evid Based Complement Alternat Med. 2(3): 285–299.
Lo HC, Wasser SP. (2011). Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems (review). Int J Med Mushrooms. 13(5):401-26
Ma D, Feng N, Feng AP, Han W, Tan Q. (2016).Biological activities of organic solvent extract from Volvariella volvacea at different growth stages. Jun Wu Xue Bao. 35(10): 1226‐1233
Machann J, Thamer C, Schnoedt B, (2005). Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI/MRS study. MAGMA. 18(3):128–137
Masjedi F, Gol A, Dabiri S. (2013). Preventive Effect of Garlic (Allium sativum L.) on Serum Biochemical Factors and Histopathology of Pancreas and Liver in
Streptozotocin- Induced Diabetic Rats. Iran J Pharm Res. 12(3):325-38
Masuko T, Minami A, Iwasaki N, Majima T, Nishimura S, Lee YC (2005). Carbohydrate analysis by a phenol–sulfuric acid method in microplate format. Anal Biochem. 339(1):69-72.
Mau JL, Lai YC, Wang NP, Chen CC, Chang CH, Chyau CC. (2003). Composition and antioxidant activity of the essential oil from Curcuma zedoary. Food Chem. 82: 583-591.
McMacken M, Shah S. (2017). A plant-based diet for the prevention and treatment of type 2 diabetes. J Geriatr Cardiol. 14(5): 342–354
Milner JA. Reducing the risk of cancer. In: Goldberg I., editor. Functional Foods: Designer Foods, Pharmafoods, Nutraceuticals. Chapman & Hall; New York, NY, USA: pp. 39-70.
Monzote L, Piñón A, Setzer WN.( 2014). Antileishmanial Potential of Tropical Rainforest Plant Extracts. Medicines (Basel). 1(1):32-55.
Naso FC, Mello RN, Bona S, Dias AS, Porawski M, Ferraz A, Richter MF, Marroni NP. (2010). Effect of Agaricus blazei Murill on the Pulmonary Tissue of Animals with Streptozotocin-Induced Diabetes. Exp Diabetes Res. 2010:543926.
Nimse SB and Pa D (2015). Free radicals, natural antioxidants, and their reaction mechanisms. Royal society of chemistry, 27986-28006
Ostlund RE, Racette SB, Stenson WF. (2003). Inhibition of cholesterol absorption by Phytosterol-replete wheat germ compared with Phytosteroldepleted wheat germ. Am J Clin Nutr. 77(6): 1385–9.
Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B (2015). Antioxidant Strategies in the Management of Diabetic Neuropathy. Biomed Res Int. 2015:515042.
Panthong S, Boonsathorn N, Chuchawankul S. (2016). Antioxidant activity, anti-proliferative activity, and amino acid profiles of ethanolic extracts of edible mushrooms. Genet Mol Res. 15(4).
Paterson RR. (2006). Ganoderma - a therapeutic fungal biofactory. Phytochemistry. 67(18):1985-2001.
Phan CW, Lee GS, Hong SL, Wong YT, Brkljača R, Urban S, Abd Malek SN, Sabaratnam V. (2014). Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways. Food Funct. 5(12):3160-9.
Poitout V, Tanaka Y, Reach G, Robertson RP. (2001). Oxidative stress, insulin secretion, and insulin resistance. Journ Annu Diabetol Hotel Dieu. 2001:75-86.
Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine. 26: 1231-1237
Ribeiro B, Andrade PB, Silva BM, Baptista P, Seabra RM, Valentão P. (2008). Comparative study on free amino acid composition of wild edible mushroom species. Journal of Agricultural and Food Chemistry. 56(22):10973–10979.
Robbins RJ (2003). Phenolic acids in foods: an overview of analytical methodology. J Agric Food Chem. 51(10):2866-87.
Robertson RP (2006). Oxidative stress and impaired insulin secretion in type 2 diabetes. Curr Opin Pharmacol. 6(6):615-9.
Robertson RP, Harmon JS. (2006). Diabetes, glucose toxicity, and oxidative stress: A case of double jeopardy for the pancreatic islet beta cell. Free Radic Biol Med. 15;41(2):177-84.
Shapiro K, Gong WC. (2002). Natural Products Used for Diabetes. J Am Pharm Assoc. 42(2): 217-226.
Shirosaki M, Koyama T. Laminaria japonica as a food for the prevention of obesity and diabetes. Adv Food Nutr Res. 64:199-212.
Shimada K., Fujikawa K., Yahara K., Nakamura T. (1992). Antioxidative properties of xanthone on the auto oxidation of soybean in cylcodextrin emulsion. J Agr Food Chem. 40:945–948.
Shimozu Y, Kuroda T, Tsuchiya T, Hatano T. (2017). Structures and Antibacterial Properties of Isorugosins H-J, Oligomeric Ellagitannins from Liquidambar formosana with Characteristic Bridging Groups between Sugar Moieties. J Nat Prod. 80(10):2723-2733.
Shubrook JH, Jr., Johnson AW. (2011). An osteopathic approach to type 2 diabetes mellitus. J Am Osteopath Assoc. 111(9):531–537.
Singh V, Bedi GK, Shri R .(2017). In Vitro and In Vivo Antidiabetic Evaluation of Selected Culinary-Medicinal Mushrooms (Agaricomycetes). Int J Med Mushrooms. 19(1):17-25.
Snedeker SM, Hay AG. (2012). Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? Environ Health Perspect. 120(3):332–339.
Stalikas CD. (2007). Extraction, separation, and detection methods for phenolic acids and flavonoids. J Sep Sci. 30(18):3268-95.
Takeujchi H, He P, Mooi LY. (2004) Reductive effect of hot-water extracts from woody ear (Auricularia auricula-judae Quel.) on food intake and blood glucose concentration in genetically diabetic KK-Ay mice. J Nutr Sci Vitaminol (Tokyo). 50(4):300-4.
Takaku T, Kimura Y, Okuda T. (2001). Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action. J Nutr. 131: 1409.
Tai A, Ohno A, Ito H. (2016). Isolation and Characterization of the 2,2′-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) Radical Cation-Scavenging Reaction Products of Arbutin. J. Agric. Food Chem, 64 (38), 7285–7290.
Tibaut M, Petrovič D. (2016). Oxidative Stress Genes, Antioxidants and Coronary Artery Disease in Type 2 Diabetes Mellitus. Cardiovasc Hematol Agents Med Chem. 14(1):23-38.
Tsao R. (2010). Chemistry and Biochemistry of Dietary Polyphenols. Nutrients. 2(12): 1231-1246
Tsao R, Yang R. (2003). Optimization of a new mobile phase to know the complex and real polyphenolic composition: towards a total phenolic index using high-performance liquid chromatography. J Chromatogr A. 1018(1):29-40.
Tung YT, Chang ST. (2010). Inhibition of Xanthine Oxidase by Acacia confusa Extracts and Their Phytochemicals. J. Agric. Food Chem.. 58 (2), 781–786.
Tung YT, Wu JH, Huang CC, Peng HC, Chen YL, Yang SC, Chang ST. (2009). Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats. Food Chem Toxicol. 47(6):1385-92.
Vitak TY, Wasser SP, Nevo E, Sybirna NO. (2015). The Effect of the Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum (Higher Basidiomycetes) on the Erythron System in Normal and Streptozotocin-Induced Diabetic Rats. Int J Med Mushrooms. 17(3):277-86.
Wasser SP. (2011). Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol. 89(5):1323-32.
Wang PC, Zhao S, Yang BY, Wang QH, Kuang HX (2016). Anti-diabetic polysaccharides from natural sources: a review. Carbohydrate polymers. 148: 86-97.
Wang K, Li B, Ma K, Liu N, Huang Y, Ren JW, Wanga WH, Liu HW, (2015). Eight new alkaloids with PTP1B and α-glucosidase inhibitory activities from the medicinal mushroom Hericium erinaceus. Tetrahedron. 71(51), 9557-9563.
Wang XL, Dou M, Luo Q, Cheng LZ, Yan YM, Li RT, Cheng YX. (2017). Racemic alkaloids from the fungus Ganoderma cochlear. Fitoterapia. 116:93-98.
Witzum JL. (1994). The oxidative hypothesis of atherosclerosis. Lancet. 344: 793-795.
Wu J, Shi S, Wang H, Wang S. (2016). Mechanisms underlying the effect of polysaccharides in the treatment of type 2 diabetes: A review. Carbohydr Polym. 144:474-94.
Xu LJ, Wang QG , Wang GQ, Wu JY. (2016). Antioxidant Activities of Polysaccharides in 14 Wild Mushroom Species from the Forest of Northeastern China. Int J Med Mushrooms. 17(12):1161-70.
Yang JH, Lin HC and Mau JL. (2002). Antioxidant properties of several ommercial mushrooms. Food Chem. 77: 229-235.
Yang BK, Park JB and Song CH. (2003). Hypolipidemic effect of exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus. Biosci Biotechnol Biochem. 67(6): 1292-1298.
Yang BK, Kim DH, Jeong SC, Das S, Choi YS, Shin JS, Lee SC, Song CH. (2002). Hypoglycemic effect of a Lentinus edodes exo-polymer produced from a submerged mycelial culture. Biosci Biotechnol Biochem. 66(5):937-42.
Yi Z, Shao-Long Y, Ai-Hong W, Zhi-Chun S, Ya-Fen Z, Ye-Ting X, Yu-Ling H. (2015). Protective Effect of Ethanol Extracts of Hericium erinaceus on Alloxan-Induced Diabetic Neuropathic Pain in Rats. Evid Based Complement Alternat Med. 2015:595480.
Yuan XQ, Gu XH, Tang J, Wasswa J. (2008). Hypoglycemic effect of semipurified peptides from Momordica charantia L. Var. abbreviata Ser. In alloxan-induced diabetic mice. J Food Biochem. 32: 107-121.
Yu ZQ, Li XD, Xu XY (2011). The hypoglycemic effect of Laminaria japonica on diabetic model induced by alloxan in rats. Chinese Pharmacological Bulletin. 27(5):651–655.
Zhao R, Li QW, Li J, Zhang T. (2009). Protective effect of Lycium barbarum polysaccharide 4 on kidneys in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol. 87(9), 711–719.
Zhang Y, Li Q1, Wang J, Cheng 2, Huang X, Cheng Y, Wang K. (2016). Polysaccharide from Lentinus edodes combined with oxaliplatin possesses the synergy and attenuation effect in hepatocellular carcinoma. Cancer Lett. 377(2):117-25.
Zhou K,Chen Y, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF. (2009). Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci USA. 106(10):3907-12.
Zhu CL, Ma JX. (2014). Chemical constituents of Mallotus paniculatus. Zhong Yao Cai. 37(8):1385-7.