12 スリランカ産天然薬物"Kotala himbutu" (Salacia reticulata) の抗糖尿病作用成分 : 新奇なチオ糖スルホニウム硫酸分子内塩構造を有するα-グルコシダーゼ阻害成分Salacinol及びKotalanolの構造(口頭発表の部)

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The roots and stems of Salacia reticulata WIGHT ("Kotala himbutu" in Singhalase, Celastraceae) have been extensively used as a specific remedy for diabetes in Ayurvedic system in Indian traditional medicine. As a continuing part of our screening for antidiabetogenic principles of natural medicine and medicinal foods, we have found that the water-soluble fractions from the roots and stems of S. reticulata strongly inhibited the increase of serum glucose levels after the administration of sucrose or maltose, but not glucose, in rats. Furthermore, the fractions inhibited rat intestinal maltase and sucrase in vitro, although the extract even at high dose did not have any effect on experimental hyperglycemia induced by injection of alloxan in mice. On the other hand, the lipophilic fraction showed inhibitory activity for rat lens aldose reductase and, as the active components, new triterpene kotalagenin 16-acetate (5) was isolated together with several diterpenes and triterpenes. Through bioassay-guided separation, two potent α-glucosidase inhibitors called salacinol (1, 0.0079%) and kotalanol (4, 0.0002%) have been isolated from the water-soluble fraction together with many sugars and glycosides. The absolute stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the alkaline degradation to 1-deoxy-4-thio-D-arabinofuranose (2) and the X-ray crystallographic analysis. The molecular conformation showed the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1-deoxy-D-erythrosyl-3-sulfate anion. The structure of kotalanol was also elucidated in a similar manner as that of 1 to be the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1-deoxyheptosyl-3-sulfate anion. Salacinol (1) and kotalanol (4) were found to exhibit the competitive inhibition for the intestinal α-glucosidase of rat. Their inhibitory activities against sucrase and maltase were nearly equal to those of a commercial α-glucosidase inhibitor acarbose, whereas their activities against isomaltase were much more potent than that of acarbose. 1-Deoxy-4-thio-D-arabinofuranose (2) lacked the activity (IC_<50>>400 μg/ml) and its methyl sulfonium iodide (3) showed weak activity (sucrase: IC_<50> 129 μg/ml; maltase: IC_<50>>400μg/ml). This evidence revealed that the spiro-like inner salt structure of 1 and 4 was essential for the potent α-glucosidase inhibitory activity. Furthermore, 1 more strongly inhibited the increase of serum glucose levels in sucrose-loaded rats than acarbose.
天然有機化合物討論会の論文
1998-08-31

12 スリランカ産天然薬物"Kotala himbutu" (Salacia reticulata) の抗糖尿病作用成分 : 新奇なチオ糖スルホニウム硫酸分子内塩構造を有するα-グルコシダーゼ阻害成分Salacinol及びKotalanolの構造(口頭発表の部)

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