伪-Glucosidase Inhibitors from Brickellia cavanillesii

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• 作者：Sonia Escand贸n-Rivera ; Martin Gonz谩lez-Andrade ; Robert Bye ; Edelmira Linares ; Andr茅s Navarrete ; Rachel Mata
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：May 25, 2012
• 年：2012
• 卷：75
• 期：5
• 页码：968-974
• 全文大小：491K
• 年卷期：v.75,no.5(May 25, 2012)
• ISSN：1520-6025

文摘

An aqueous extract from the aerial parts of Brickellia cavanillesii attenuated postprandial hyperglycemia in diabetic mice during oral glucose and sucrose tolerance tests. Experimental type-II DM was achieved by treating mice with streptozotocin (100 mg/kg) and 尾-nicotinamide adenine dinucleotide (40 mg/kg). These pharmacological results demonstrated that B. cavanillesii is effective for controlling fasting and postprandial blood glucose levels in animal models. The same aqueous extract also showed potent inhibitory activity (IC₅₀ = 0.169 vs 1.12 mg/mL for acarbose) against yeast 伪-glucosidase. Bioassay-guided fractionation of the active extract using the 伪-glucosidase inhibitory assay led to the isolation of several compounds including two chromenes [6-acetyl-5-hydroxy-2,2-dimethyl-2H-chromene (1) and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2)], two sesquiterpene lactones [caleins B (3) and C (4)], several flavonoids [acacetin (5), genkwanin (6), isorhamnetin (7), kaempferol (8), and quercetin (9)], and 3,5-di-O-caffeoylquinic acid (10). Chromene 2 is a new chemical entity. Compounds 2, 4, 7, and 9 inhibited the activity of yeast 伪-glucosidase with IC₅₀ 0.42, 0.28, 0.16, and 0.53 mM, respectively, vs 1.7 mM for acarbose. Kinetic analysis revealed that compounds 4 and 7 behaved as mixed-type inhibitors with K_i values of 1.91 and 0.41 mM, respectively, while 2 was noncompetititive, with a K_i of 0.13 mM. Docking analysis predicted that these compounds, except 2, bind to the enzyme at the catalytic site.