Yanyan Zhang1, Hongxia Zhang2, Feng Wang2, Dandan Yang2, Ke Ding1, Junfeng Fan3. 1. Food Science and Engineering College, Beijing University of Agriculture, Beijing, China. 2. College of Bioscience and Biotechnology, Beijing Forestry University, Beijing, China. 3. College of Bioscience and Biotechnology, Beijing Forestry University, Beijing, China. Electronic address: fanjunfeng@bjfu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The cortex and leaves of Eucommia ulmoides Oliv. from the family Eucommiaceae are traditional Chinese medicines (TCM). Roasted Eucommiae cortex is utilized to reinforce the muscles and lungs, lower blood pressure and improve the tone of the liver and kidneys, while Eucommia ulmoides leaves (EUL) are traditionally used as folk remedies to treat diabetes. MATERIALS AND METHODS: EUL extract, obtained by ethanol (40%) was loaded onto an AB-8 macroporous resin column, and washed thoroughly with 0, 20, 40, 60, and 80% (v/v) ethanol for purification. The ethanol eluents of EUL were first determined to inhibit α-glucosidase in vitro, and then the inhibition of the most potent eluent, i.e., 20% ethanol eluent of EUL (EEUL), against carbohydrate-degrading enzymes and glucose transport in Caco-2 cells was demonstrated. And computational modeling was also employed to evaluate the binding modes of compounds identified in EEUL by GC-MS analysis. RESULTS: EEUL significantly inhibited α-glucosidase (43.08±0.55%) competitively in vitro and concentration-dependently suppressed sucrase (IC50, 0.07mg/mL) and maltase (IC50, 0.53mg/mL) in Caco-2 cells. The inhibitory activity of EEUL (0.02mg/mL) on sucrase and maltase was identical to that of acarbose (0.02mg/mL). Moreover, 1.0mg/mL EEUL decreased glucose transport in cells by 26.25±0.86%. GC-MS revealed that EEUL was rich in monosaccharides, polyphenols and esters, which comprised 47.16% of the total extract. Computational modeling showed that catechin, α-d-glucopyranose and d-mannono-1,4-lactone docked tightly into the sucrase active site with low binding energies. CONCLUSION: These results indicated that EEUL exerted marked anti-hyperglycemic effects by suppressing disaccharidases and glucose transporters. Therefore, EUL is a beneficial source of inhibitors of carbohydrate-utilizing enzymes, glucose transporters, and potentially hyperglycemia.
ETHNOPHARMACOLOGICAL RELEVANCE: The cortex and leaves of Eucommia ulmoides Oliv. from the family Eucommiaceae are traditional Chinese medicines (TCM). Roasted Eucommiae cortex is utilized to reinforce the muscles and lungs, lower blood pressure and improve the tone of the liver and kidneys, while Eucommia ulmoides leaves (EUL) are traditionally used as folk remedies to treat diabetes. MATERIALS AND METHODS: EUL extract, obtained by ethanol (40%) was loaded onto an AB-8 macroporous resin column, and washed thoroughly with 0, 20, 40, 60, and 80% (v/v) ethanol for purification. The ethanol eluents of EUL were first determined to inhibit α-glucosidase in vitro, and then the inhibition of the most potent eluent, i.e., 20% ethanol eluent of EUL (EEUL), against carbohydrate-degrading enzymes and glucose transport in Caco-2 cells was demonstrated. And computational modeling was also employed to evaluate the binding modes of compounds identified in EEUL by GC-MS analysis. RESULTS: EEUL significantly inhibited α-glucosidase (43.08±0.55%) competitively in vitro and concentration-dependently suppressed sucrase (IC50, 0.07mg/mL) and maltase (IC50, 0.53mg/mL) in Caco-2 cells. The inhibitory activity of EEUL (0.02mg/mL) on sucrase and maltase was identical to that of acarbose (0.02mg/mL). Moreover, 1.0mg/mL EEUL decreased glucose transport in cells by 26.25±0.86%. GC-MS revealed that EEUL was rich in monosaccharides, polyphenols and esters, which comprised 47.16% of the total extract. Computational modeling showed that catechin, α-d-glucopyranose and d-mannono-1,4-lactone docked tightly into the sucrase active site with low binding energies. CONCLUSION: These results indicated that EEUL exerted marked anti-hyperglycemic effects by suppressing disaccharidases and glucose transporters. Therefore, EUL is a beneficial source of inhibitors of carbohydrate-utilizing enzymes, glucose transporters, and potentially hyperglycemia.