山莴苣过长沙与甜菊之活成分探索.ppt

山萵苣，過長沙與甜菊之活性成分探索,隨著台灣人口的日趨老化及生活形態改變，糖尿病的罹患率也逐漸增加。目前雖有胰島素注射劑及口服降血糖藥物，但在臨床上之使用仍未達理想。然而，我國傳統醫學在幾千年以前就有關於糖尿病的記載，並由於長期的實務亦累積了豐富的治療經驗。在民間有許多中藥或藥用植物被傳承使用，而這些藥物大部份仍未以科學方法加以探討及確立其藥效。因此擬對常用之降血糖中藥及藥用植物進行探討，期望尋得先導化合物以供新藥開發之依據。山萵苣(Lactuca indica Linn.)為菊科(Compositae)草本植物，而過長沙(Bacopa monnieri (Linn.) Wettstein)為玄參科植物(Scrophulariaceae)，在初步篩選中發現此二種植物之萃取液具有顯著之降血糖活性，具進一步探討之價值，因此，進行此二種植物之有效成分分離。經由各種管柱層析，自山萵苣全草之70%丙酮萃取液分離出13個化合物，其中四個屬於新化合物，其構造經光譜資料分析及化學方法確認為lactucain A (10), lactucain B (11), lactucain C (12)及lactucaside (13)。過長沙全草以甲醇萃取後經各種管柱層析，共分離得到24個化合物，其中包含五個新化合物，其構造經確認為bacopaside III (18), bacopasaponin G (19), bacopaside A (21), bacopaside B (28)及bacopaside C (30)。將山萵苣及過長沙分離之成分進行降血糖活性試驗，其結果發現lactucain C (12), lactucaside (13), luteolin 7-O-b-D-glucuronide (6), calcerorioside B (25)及caffeic acid (31)呈現明顯之活性。另外，並進行降血壓活性之篩選，得到quercetin (1), bacopasaponin C (14)及bacopasapnin G (19)具有顯著的活性。Stevioside為菊科植物甜菊(Stevia rebaudiana (Bertoni) Hemsl.)葉片中萃取而得，可作為甜味劑之成分，isosteviol則為stevioside經由酸水解後所得之化合物，具有降血糖及降血壓等活性。為了進一步探討isosteviol衍生物之活性，利用微生物轉換技術於isosteviol之結構導入hydroxy group。經由篩選30種菌種後，選出以Cunninghamella bainieri, Actinoplanes sp., Mucor recurvatus及Cunninghamella blakesleeana進行微生物轉換，得到8個代謝物，經由各種光譜數據加以解析，確認其中ent-11,12-dihydroxy-16-ketobeyeran-19-oic acid (39), ent-11,12,17-trihydroxy-16-ketobeyeran-19-oic acid (40), ent-12,15-dihydroxy -16-ketobeyeran-19-oic acid (41), ent-7,15-dihydroxy-16-ketobeyeran-19-oic acid (42)及ent-9-hydroxy-16-ketobeyeran-19-oic acid (43) 5個代謝物為新化合物。將所得代謝物進行降血糖及降血壓活性試驗，其結果發現化合物38仍具有輕微的降血糖活性，而化合物43具降血壓活性，但均較isosteviol的活性弱。,Studies on the Active Components from Lactuca indica, Bacopa monnieri and Stevia rebaudiana,Because the elderly population has been gradually increasing and life style changes, the mortality rate pertaining to diabetes mellitus has significantly raised in Taiwan. Currently, the use of insulin injections and oral hypoglycemic agents failed to control this disease effectively. In China, the Chinese medicine has been outstanding on the treatment of diabetes for thousand years. Although several folk medicines for the diabetes are useful, most of them need to establish their effectiveness. In this study, we would like to search the active principles and evaluate clinical use to serve as lead compound for the development of the novel antidiabetic drugs. In our preliminary screening tests, we found that the extracts of Lactuca indica (Compositae) and Bacopa monnieri (Scrophulariaceae) exhibited apparent hypoglycemic activities. The fresh L. indica was extracted with 70% acetone and repeatedly chromatographed, resulted in the isolation of thirteen compounds including four new compounds. Based on the spectroscopic data and chemical analysis, the structures of these new compounds were determined as lactucain A (10), lactucain B (11), lactucain C (12), and lactucaside (13). The whole plant material of B. monnieri was extracted with MeOH. By means of various column chromatographic separations, twenty-four compounds were isolated including five new compounds. Their structures were elucidated as bacopaside III (18), bacopasaponin G (19), bacopasides A (21), bacopasides B (28), and bacopasides C (30) by spectral and chemical methods. We have tested all compounds isolated from L. indica and B. monnieri for antihyperglycemic and antihypertensive activities. Six compounds, lactucain C (12), lactucaside (13), luteolin 7-O-b-D-glucuronide (6), calcerorioside B (25), and caffeic acid (31) have shown the remarkable antihyperglycemic activities. Furthermore, quercetin (1), bacopasaponin C (14), and bacopasapnin G (19) have displayed the pronounced antihypertensive activities. Stevioside was extracted from the leaves of Stevia rebaudiana (Compositae) and used as a natural sweetening agent. Isosteviol was obtained by acid hydrolysis of stevioside containing antidiabetic and antihypertensive activities. In order to study the bioactivity of isosteviol derivatives, microbial transformations have been used to introduce hydroxyl groups on the structure of isosteviol. By screening thirty microorganisms, Cunninghamella bainieri, Actinoplanes sp., Mucor recurvatus, and Cunninghamella blakesleeana were selected for the biotransformation of isosteviol and obtained eight metabolites. Among them, five metabolites are the new compounds, including ent-11,12-dihydroxy-16-ketobeyeran-19-oic acid (39), ent-11,12,17-trihydroxy-16-ketobeyeran-19-oic acid (40), ent-12,15-dihydroxy-16-ketobeyeran-19-oic acid (41), ent-7,15-dihydroxy-16-ketobeyeran-19-oic acid (42), and ent-9-hydroxy-16-ketobeyeran-19-oic ac