匙羹藤茎抗糖尿病药效物质基础研究
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摘要
目的:研究萝藦科(Asclepiadaceae)匙羹藤属(Gymnema)匙羹藤Gymnema sylvestre (Retz.) Schult茎的化学成分。重点是确定匙羹藤茎的药效部位,并从药效部位中分离单体化合物,确定单体化合物的分子结构。
方法:利用萃取、大孔树脂柱色谱法对匙羹藤茎化学成分进行提取与初步分离,通过体外非酶糖化抑制反应确定其有效部位。通过硅胶柱色谱、反相硅胶柱色谱、重结晶、高效制备液相等多种方法对有效部位进行分离纯化,并进一步通过化学方法和现代波谱技术(1~H NMR,(13)~C NMR, APCI-MS , MALDI/ TOF-MS等)对其单体成分进行结构鉴定,确定单体化合物的结构。
结果:分离得到8个化合物,经波谱鉴定结构分别为:化合物Ⅰ:牛弥菜醇A;化合物Ⅱ:豆甾醇;化合物Ⅲ:羽扇豆醇;化合物Ⅳ:豆甾醇3-O-β-D-葡萄糖苷;化合物Ⅴ:22-羟基-长刺皂苷元3-O-β-D-吡喃葡萄糖醛酸基-28-O-α-L-吡喃鼠李糖苷的钠盐;化合物Ⅵ:22-羟基-长刺皂苷元3-O-β-D-吡喃葡萄糖基(1→3)-β-D-吡喃葡萄糖醛酸基-28-O-α-L-吡喃鼠李糖苷的钠盐;化合物Ⅶ:齐墩果酸3-O-β-D-吡喃葡萄糖基(1→6)-β-D-吡喃葡萄糖苷;化合物Ⅷ:16,22-二羟基-齐墩果-12-烯-3-O-β-D-吡喃木糖基(-1→6)-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷。
结论:化合物Ⅲ、Ⅴ、Ⅵ、Ⅶ、Ⅷ首次从该属植物中分离得到。化合物Ⅴ、Ⅵ、Ⅶ、Ⅷ是从药效部位分离得到,可用于构效关系研究。
Purpose: To study the chemical constituents from the stems of Gymnema sylvestre(Retz.)Schult. The key is to confirm the efficacy of medicine part and elucidate the compounds structure which was isolated from the stems of Gymnema sylvestre.
Method: Proceed to Extract different polarity parts to be certained active sites through nonenzymatic glycosylation inhibit reaction from the stems of Gymnema sylvestre. Eight compounds were isolated by the modern chromatography techniques (macroporous resin, ODS and HPLC, prep-HPLC etc) from the stems of Gymnema sylvestre. Their structures were elucidated by the spectroscopic analysis (1~HNMR, (13)~CNMR, APCI-MS,MALDI/TOF-MS) and chemical methods.
Result: Eight compounds were isolated from the the stems of Gymnema sylvestre (Retz.) Schult. These compounds were identified as Conduritol A (Ⅰ),Stigmasterol (Ⅱ), Lupeol(Ⅲ),Stigmasterol3-O-β-D-glucoside(Ⅳ),The sodium of22-hydroxy-longisipinogenin3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopynosid e(Ⅴ), The sodium of22-hydroxy-longisipinogenin3-O-β-D-glucopyranosyl-(1→3)-β-D-glucuronopyranosyl-28-O-α-L-rhamnopynoside(Ⅵ),Oleanlicacid3-O-β-D-glucopyranosyl(1→6)-β-D-glucopyranside(Ⅶ),16-22-dihydroxy-olean-12-ene-3-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (Ⅷ).
Conclusion: CompoundsⅢ,Ⅴ,Ⅵ,Ⅶ, andⅧwere obtained from this plant for the first time. And CompoundsⅤ,Ⅵ,Ⅶ, andⅧwere obtained from the active site which can be used for structure-activity relationship study.
方法:利用萃取、大孔树脂柱色谱法对匙羹藤茎化学成分进行提取与初步分离,通过体外非酶糖化抑制反应确定其有效部位。通过硅胶柱色谱、反相硅胶柱色谱、重结晶、高效制备液相等多种方法对有效部位进行分离纯化,并进一步通过化学方法和现代波谱技术(1~H NMR,(13)~C NMR, APCI-MS , MALDI/ TOF-MS等)对其单体成分进行结构鉴定,确定单体化合物的结构。
结果:分离得到8个化合物,经波谱鉴定结构分别为:化合物Ⅰ:牛弥菜醇A;化合物Ⅱ:豆甾醇;化合物Ⅲ:羽扇豆醇;化合物Ⅳ:豆甾醇3-O-β-D-葡萄糖苷;化合物Ⅴ:22-羟基-长刺皂苷元3-O-β-D-吡喃葡萄糖醛酸基-28-O-α-L-吡喃鼠李糖苷的钠盐;化合物Ⅵ:22-羟基-长刺皂苷元3-O-β-D-吡喃葡萄糖基(1→3)-β-D-吡喃葡萄糖醛酸基-28-O-α-L-吡喃鼠李糖苷的钠盐;化合物Ⅶ:齐墩果酸3-O-β-D-吡喃葡萄糖基(1→6)-β-D-吡喃葡萄糖苷;化合物Ⅷ:16,22-二羟基-齐墩果-12-烯-3-O-β-D-吡喃木糖基(-1→6)-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷。
结论:化合物Ⅲ、Ⅴ、Ⅵ、Ⅶ、Ⅷ首次从该属植物中分离得到。化合物Ⅴ、Ⅵ、Ⅶ、Ⅷ是从药效部位分离得到,可用于构效关系研究。
Purpose: To study the chemical constituents from the stems of Gymnema sylvestre(Retz.)Schult. The key is to confirm the efficacy of medicine part and elucidate the compounds structure which was isolated from the stems of Gymnema sylvestre.
Method: Proceed to Extract different polarity parts to be certained active sites through nonenzymatic glycosylation inhibit reaction from the stems of Gymnema sylvestre. Eight compounds were isolated by the modern chromatography techniques (macroporous resin, ODS and HPLC, prep-HPLC etc) from the stems of Gymnema sylvestre. Their structures were elucidated by the spectroscopic analysis (1~HNMR, (13)~CNMR, APCI-MS,MALDI/TOF-MS) and chemical methods.
Result: Eight compounds were isolated from the the stems of Gymnema sylvestre (Retz.) Schult. These compounds were identified as Conduritol A (Ⅰ),Stigmasterol (Ⅱ), Lupeol(Ⅲ),Stigmasterol3-O-β-D-glucoside(Ⅳ),The sodium of22-hydroxy-longisipinogenin3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopynosid e(Ⅴ), The sodium of22-hydroxy-longisipinogenin3-O-β-D-glucopyranosyl-(1→3)-β-D-glucuronopyranosyl-28-O-α-L-rhamnopynoside(Ⅵ),Oleanlicacid3-O-β-D-glucopyranosyl(1→6)-β-D-glucopyranside(Ⅶ),16-22-dihydroxy-olean-12-ene-3-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (Ⅷ).
Conclusion: CompoundsⅢ,Ⅴ,Ⅵ,Ⅶ, andⅧwere obtained from this plant for the first time. And CompoundsⅤ,Ⅵ,Ⅶ, andⅧwere obtained from the active site which can be used for structure-activity relationship study.
引文
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[25]江海燕.匙羹藤降血糖成分研究进展[J].中药材,2003;26(4):305-307.
[26]廖丹葵,徐庶,韦藤幼,等.超声提取匙羹藤总皂苷工艺的研究[J].中成药,2010;32(3):497-499.
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[28]王英,冯易君,王晓玲,等.匙羹藤叶中一种新成分的分离和鉴定[J].华西药学杂志,2004;19(5): 336-338.
[29]卢汝梅,曹敏,韦建化,等.匙羹藤中牛弥菜醇A提取工艺研究[J].中药材,2009;32(5):807-809.
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[31]覃俊佳.匙羹藤酸降血糖作用的研究[J].中国中医药信息杂志,2000;7(3):28-31.
[32] Baskaran K. Antidiabetic effect of a leaf extract from Gymnema sylvestre innon-insulin-dependent diabetes mellitus patients[J]. Ethnopharmaco, 1990;30: 295-300.
[33] AnPumaBishayee,Walay chatterjee. HpyoliPidaemic and Antihateorselerotic Eeffets of Oarl Gymnema syIvesert R.Br leaf Exrtact in albino Rats Fedona High Fat Diet[J]. Phytohter Res, 1994;8: 118-120.
[34] Wang LF. Inhibitory effect of gemnemic acid on intestinal absoprtion of oleic acid in rats[J].Can J Phyarmacol,1998;31(3):1017-1023.
[35]朱家谷,陈有根,李慧,等.匙羹藤复方冲剂降糖降脂作用研究[J].中成药,1997;19(8):38-40.
[36] Luo Hong. Possible participation of NO and EDHF in therelaxation of rat intestinal cirular muscle induced by Gymnema water extracts containing Gymnemic acids[J]. Yon-ago Igaku Zasshi, 1999; 50(1): 22-25.
[37] Inoue Tomoaki, Ohfuji Masumi, Komatsu Masamoto. An-tioxidative effect of infusions of green tea and“health tea”[J]. Kyotofu Hoken Kankyo Kenkyusho Nenpo, 1997; 42(1): 7-9.
[38] Sawabe Yoshiyuki, Nakagomi Kazuya, Iwagami Shozo, etc. Inhibitory effects of pectic substances on activatedhyaluronidase and histamine release from mast cells [J]. Biochim Biophys Acta, 1992;1137(3): 274-276.
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[2] FujimotoTadashi, NagaiToshikazu, YamashitaFumio, etc. Physiological activating substances isolated from Gymnema sylvestre[J].Seito Gijutsu Kenkyu Kaishi, 1991; 39(2): 71-73.
[3]甄汉深,马利飞,唐伯灵,等.匙羹藤的生药鉴定[J].中药材,1997;20(2): 70-72.
[4]江苏新医学院.中药大辞典(上册)[M].上海:上海人民出版社,1977,第一版:1246.
[5]韦宝伟,施骞.匙羹藤的研究概况[J].国外医药.植物药分册,1996;11(3): 107-110.
[6]中国科学院中国植物志编辑委员会.中国植物志[M].北京:科学出版社,第二版:1982;63(1):418-419.
[7] Yoshikawa. Structure studies of new antisweet constituents from Gymnema sylvestre[J]. Tetrahedron Letters, 1989; 30(9): 1103-1106.
[8] Maeda M. Studies on taste modifiers.Ⅱ. Purification andstructure determination of gymnemic acids, antisweet active principle from Gymnema sylvestre leaves[J]. Tetrahedron Lett, 1989; 30(12): 1547-1550.
[9] Yoshikawa K. Antisweet natural products .IX Structures of gymnemic acids XV-XVⅢfrom Gymnema sylvestre R.Br[J]. Chem. Pharm. Bull., 1993; 41(10): 1730-1732.
[10] Kiuchi F. Two new gymnemis acid congeners congtaining ahexulopyranside moiety[J]. Chem. Pharm. Bull., 1990; 38(8): 2326-2328.
[11] Kazuko Y. Antisweet natural productsⅤ. structures of Gymnemic acidsⅧ-ⅩⅢfrom GS [J].Chem. Pharm.Bull,1992; 40(7): 1779-1782.
[12] Kazuko Y. A new type antisweet principles occurring in Gymnema sylvestre [J]. Tetrahedron Letters, 1991; 32(6): 789-792.
[13] Yoshikawa K. Gymnemic acidⅤ.ⅥandⅦfrom Gur-Ma, the leaves of Gymnema sylvestre R.Br[J]. Chem. Pharm. Bull, 1989; 37(3): 852-854.
[14] Niranjian P. Shahu. Triterpenoid saponins from Gymnema sylvestre[J]. Phytochemistry, 1996; 41(4): 1181-1185.
[15] Yoshikawa Masayuki. Medicinal foodstuffs X. Structures of new triterpene glycosides, gymnemosides -c, d,-e, and -f, from the leaves of Gymnema sylvestre R.Br.: influence ofGymnema glycosides on glucose uptake in rat small intestinal fragments[J]. Chem. Pharm. Bull., 1997; 45(12): 2034-2038.
[16] Kazuko Y. Antisweet Natural Products.ⅩⅢ.Structures of Alternosides I-X from Gynmema alternifolium[J].Chem.Pharm.Bull.,1998; 46(7):1102-1107.
[17] Wen-Cai Ye. Oleanane saponins from Gymnema sylvestre[J]. Phytochemistry, 2000; 53(8): 893-899.
[18] Wen-Cai Ye. Antisweet saponins from Gymnema sylvestre. Journal of Natural Proudcts, 2001;64(2): 232-235.
[19]刘欣,叶文才,徐德然,等.匙羹藤的三萜和皂甙成分研究[J].中国药科大学学报,1999;30(3):174-176.
[20] Yoshikawa M,. Medicinal Foodstuffs I-X. The inhibitors of glucose absorption from the leaves of Gymmema sylvestre R.Br. (Asclepiadaceae): strucdtures of gymnemosides a and b[J]. Chem. Pharm. Bull., 1997; 45(10): 1671-1677.
[21] Kazuko Y. Pregnane Glycosides. Gymnepregosides A-F from the roots of Gynmema alternifolium[J]. Chem.Pharm.Bull,1998;46(8):1236-1239.
[22]甄汉深,朱雪妍,卢汝梅,等.匙羹藤茎化学成分的研究[J].中药材,2008 ;31(8):1154-1156.
[23]仰榴青.匙羹藤的最新研究进展[J].江苏大学学报(医学版), 2004;14(6):545-549.
[24]甄汉深,梁洁,吴怀恩,等.匙羹藤的研究进展[J].广西中医学院学报,2004;7(1):63-66.
[25]江海燕.匙羹藤降血糖成分研究进展[J].中药材,2003;26(4):305-307.
[26]廖丹葵,徐庶,韦藤幼,等.超声提取匙羹藤总皂苷工艺的研究[J].中成药,2010;32(3):497-499.
[27]陈文彬.由匙羹藤叶制备治疗糖尿病药物的方法[P].中国专利:1475222A, 2004.
[28]王英,冯易君,王晓玲,等.匙羹藤叶中一种新成分的分离和鉴定[J].华西药学杂志,2004;19(5): 336-338.
[29]卢汝梅,曹敏,韦建化,等.匙羹藤中牛弥菜醇A提取工艺研究[J].中药材,2009;32(5):807-809.
[30]王旭华.匙羹藤治疗糖尿病研究进展[J].医学研究杂志,2009;38(1): 15-16.
[31]覃俊佳.匙羹藤酸降血糖作用的研究[J].中国中医药信息杂志,2000;7(3):28-31.
[32] Baskaran K. Antidiabetic effect of a leaf extract from Gymnema sylvestre innon-insulin-dependent diabetes mellitus patients[J]. Ethnopharmaco, 1990;30: 295-300.
[33] AnPumaBishayee,Walay chatterjee. HpyoliPidaemic and Antihateorselerotic Eeffets of Oarl Gymnema syIvesert R.Br leaf Exrtact in albino Rats Fedona High Fat Diet[J]. Phytohter Res, 1994;8: 118-120.
[34] Wang LF. Inhibitory effect of gemnemic acid on intestinal absoprtion of oleic acid in rats[J].Can J Phyarmacol,1998;31(3):1017-1023.
[35]朱家谷,陈有根,李慧,等.匙羹藤复方冲剂降糖降脂作用研究[J].中成药,1997;19(8):38-40.
[36] Luo Hong. Possible participation of NO and EDHF in therelaxation of rat intestinal cirular muscle induced by Gymnema water extracts containing Gymnemic acids[J]. Yon-ago Igaku Zasshi, 1999; 50(1): 22-25.
[37] Inoue Tomoaki, Ohfuji Masumi, Komatsu Masamoto. An-tioxidative effect of infusions of green tea and“health tea”[J]. Kyotofu Hoken Kankyo Kenkyusho Nenpo, 1997; 42(1): 7-9.
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