目的 研究块根糙苏Phlomis tuberosa的化学成分及降糖活性。方法 体内实验采用db/db糖尿病小鼠模型筛选块根糙苏的降糖活性部位。利用多种分离分析技术对活性部位进行化学分离，并应用¹H-NMR、¹³C-NMR、MS等波谱技术鉴定了化合物结构。体外二肽基肽酶-4（DPP-4）抑制活性实验对分离的化合物降糖活性进行验证。结果 醋酸乙酯部位显示出显著的降糖活性，共分离得到25个化合物，分别鉴定为β-谷甾醇（1）、豆甾醇（2）、胡萝卜苷（3）、赤桐甾醇豆甾烯二酮（4）、22-脱氢豆甾烯二酮（5）、鞣花酸（6）、没食子酸乙酯（7）、没食子酸（8）、4-羟基苯甲酸（9）、3，4-二羟基苯甲酸（10）、肉桂酸（11）、对羟基肉桂酸（12）、咖啡酸（13）、5-羟甲基糠醛（14）、奎宁酸（15）、绿原酸（16）、阿魏酸（17）、2，3-dimethoxy-5-methyl-6-（3，7，11，15，19-pentamethyl-2，6，10，14，18-eicosapentaen-1-yl）-2，5-cyclohexadiene-1，4-dione（18）、1-O-咖啡酰奎宁酸（19）、3，5-dimethoxy-4-hydroxy-benzene carbonic-1-O-β-D-glucoside（20）、2-O-丁基-α-D-呋喃果糖苷（21）、正十八烷酸（22）、油酸（23）、methyl-5-（hydroxymethyl） furan-2-carboxylate（24）、4-羟基-3-甲氧基苯甲醛（25）。其中化合物6、15、19表现出较强的DPP-4抑制活性，半数抑制浓度（IC₅₀）值分别为72.3、89.2、103.4 μmol/L，阳性药抑二肽素A IC₅₀为50 μmol/L。结论 化合物3～7、18～21为首次从该属植物中分离得到，化合物6、15、19具有抑制DPP-4的活性。

Objective To study the chemical constituents and hypoglycemic activity of Phlomis tuberosa. Methods The db/db diabetic mice was used to screen the hypoglycemic active site of P. tuberosa. The chemical constituents were isolated and purified by various separation and analysis techniques. The structures of these compounds were identified by spectroscopic analysis (¹H-, ¹³C-NMR and MS). The hypoglycemic activities of these compounds were verified by the DPP-4 inhibitory activity in vitro. Results Ethyl acetate extract of P. tuberosa showed significant hypoglycemic effect. Twenty-five compounds were isolated from the active site, containing β-stiosterol (1), stigmasterol (2), daucosterol (3), clerosterol-stigmast-4-ene-3,6-dione (4), 22-dehydro-stigmast-4-ene-3,6-dione (5), ellagic acid (6), ethyl gallate (7), gllagic acid (8), 4-hydroxybenzoic acid (9), 3,4-diohydroxybenzoic acid (10), cinnamic acid (11), p-hydroxy-cinnamic acid (12), caffeic acid (13), 5-hydromethylfuraldehyde (14), quinic acid (15), chlorogenic acid (16), ferulic (17), 2,3-dimethoxy-5-methyl-6-(3,7,11,15,19-pentamethyl-2,6,10,14,18-eicosapentaen-1-yl)-2,5-cyclohexadiene-1,4-dione (18), 1-O-caffeoyl-quinic acid (19), 3,5-dimethoxy-4-hydroxy-benzene carbonic-1-O-β-D-glucoside (20), 2-O-butyl-α-D-fructofuranoside (21), n-octadecanoic acid (22), stearic acid (23), methyl-5-(hydroxymethyl) furan-2-carboxylate (24) and 4-hydroxy-3-methoxy-benzaldehyde(25). Nine compounds were obtained from the genus Phlomis for the first time, in which ellagic acid (6), quinic acid (15), and 1-O-caffeoylquinic acid (19) showed strong DPP-4 inhibitory activity with IC₅₀ of 72.3, 89.2, and 103.4 μmol/L, respectively. The IC₅₀ of the positive drug diprotin A was 50 μmol/L. Conclusion Compounds (3-7 and 18-21) are obtained from the genus Phlomis for the first time. Compound 6, 15, and 19 show DPP-4 inhibitory activities.

R284.1

国家自然科学基金资助项目（81703682）