2021-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/696384糖尿病及嚴重威脅人類的健康，但現有藥物不僅可能具有副作用，且對其併發症無法有效改善。近年發現消化道微生物相在糖尿病的治療過程中扮演關鍵角色，例如治療第二型糖尿病的一線藥物metformin可藉由增加杯狀細胞 (goblet cells) 以及促進特定腸內菌 (如A. muciniphila) 生長，以改善糖尿病症狀。石斛是中華九大仙藥之首，具有治療糖尿病及改善其併發症的功效。金童石斛 (Dendrobium Cassiope; DC) 與金皇石斛 (D. Taiseed Tosnobile; DTT) 皆是臺灣所培育出來的中藥石斛品種，生長快速，但兩者不僅所含之葡萄甘露多醣的分子量、糖基支鏈、單糖比及乙醨化不同，其黏度、嚐味和降血糖活性亦有所不同，非常值得深入研究與探討其開發為藥用之潛力。小鼠經餵食DC與DTT多醣六週後，血糖分別降低18%及32%，且腸道中多種與糖尿病改善正相關的菌種顯著增加且負相關的菌種減少。小腸內微生物的酵素系統會將石斛葡萄甘露多醣降解成非消化性寡醣，促進小腸黏膜細胞分泌腸泌素，進而刺激胰臟分泌胰島素。然而，此類植物中非消化性寡醣的化學結構特徵與功效相關性的研究非常有限。為研究此二種臺灣特有雜交種中藥石斛之非消化性寡醣之化學組成及結構特徵及其對消化道微生物相、小腸黏膜細胞分泌腸泌素之促進效果，本計畫擬取得不同分子量之石斛甘露多醣，在建立之消化道微生物培養平台中偵測多醣降解過程以及降解物組成特性，進行非消化性寡醣的純化與分離鑑定，並評估其對腸泌素的分泌促進效果。上述研究的執行成果不但將對了解石斛非消化性寡醣之抗糖尿病的作用機轉及化學結構與功效之關係有非常大的幫助，且對開發其為抗糖尿病之新穎醣類藥物及應用消化道微生物研究平台在其他的醣類藥物開發上將有非常大的助益。 Diabetes is a serious threat to human health, but existing drugs may have side, and its complications can`t be improved effectively. Recently, gut microbiota had been found to play a key role in the treatment of diabetes. For example, the first-line drug for treatment of type II diabetes, metformin, has been found to ameliorate diabetes by increasing goblet cells and promoting the growth of specific intestinal bacteria (e.g. A. municiphila). Dendrobium, which is in the first place of the Nine Most Precious herbs in Chinese medicine, is able to treat diabetes and alleviate its complications. D. Cassiope (DC) and D. Taiseed Tosnobile (DTT) are Taiwan-cultivated hybrids that grow rapidly, however, not only their molecular weight, branches, ratio of monosaccharides and degree of acetylation for the contained glucomannans (GMs) are different, but also different in their viscosity, taste and anti-diabetic activities, which are extremely worthy to be compared and investigated in detail. After the mice were fed with the polysaccharides from DC and DTT for six weeks, the blood glucose levels were decreased 18% and 32%, respectively, and a variety of microbes positively associated with improvement in diabetes were significantly increased, and those were negatively related with improvement were reduced. The enzyme system of the small intestinal microbes will degrade the Dendrobium glucomannans into non-digestible oligosaccharides (NDOs), which may enhance the secretion of incretin the intestinal mucus cells to trigger the insulin secretion of β-cells in the pancreas. However, the studies regarding to the relationship between the functions and the chemical structural characteristics of these NDOs are very limited. To study the NDOs from the two Taiwanese Dendrobium hybrids on the interactions on gut microbiota, host incretin secretion-enhancing activity by intestinal mucus cells, the present plan is to obtain the Dendrobium GMs with different molecular weights, monitor the degradation process and the digestate profiles on the established cultural platform of gut microbes, isolate and structurally elucidate the sequence the NDOs, and evaluate on incretin secretion of intestinal mucosa cells by the oligosaccharides. Execution of the abovementioned project not only will be very helpful for a deeper understanding of the mechanisms of action and structure-functionality relationship of Dendrobium NDOs in treating diabetes, but also will be highly beneficial in developing them as new herbal anti-diabetic drug candidates, and in application of the gut microbe research platform to develop other carbohydrate drugs.抗糖尿病腸泌素寡醣石斛消化道微生物anti-diabetesincretinoligosaccharidesDendrobiumgut microbes