Morikawa Toshio, Akaki Junji, Ninomiya Kiyofumi, Kinouchi Eri, Tanabe Genzoh, Pongpiriyadacha Yutana, Yoshikawa Masayuki, Muraoka Osamu
Pharmaceutical Research and Technology Institute, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Antiaging Center, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Nutrients. 2015 Feb 27;7(3):1480-93. doi: 10.3390/nu7031480.
The antidiabetic effect of a hot water extract of stems of Salacia chinensis (SCE) was evaluated in vivo in KK-Ay mice, a typical type 2 diabetes mellitus mice model. Administration of CE-2 dietary feed containing 0.25 and/or 0.50% of SCE for three weeks to KK-Ay mice significantly suppressed the elevation of both blood glucose and HbA1c levels without significant changes in body weight or food intake. Glucose tolerance was improved by administration to KK-Ay mice for 27 days of AIN93M purified dietary feed containing 0.12% of SCE. No suppressive effect with respect to HbA1c level was observed when AIN93M/Glc dietary feed in which all digestible glucides were replaced with glucose was administered with SCE. Thus, α-glucosidase inhibitory activity approved as the mechanism of action of the antidiabetic effect of SCE by in vitro investigation was reconfirmed also in in vivo studies. Evaluation of the α-glucosidase inhibitory activity of the active constituents, salacinol (1), kotalanol (3), and neokotalanol (4), by employing human α-glucosidases revealed that these compounds inhibited them as potently (IC50 = 3.9-4.9 μM for maltase) as they inhibited rat small intestinal α-glucosidase. The principal sulfonium constituents (1-4) were highly stable in an artificial gastric juice. In addition, 1-4 were hardly absorbed from the intestine in an experiment using the in situ rat ligated intestinal loop model. The results indicate that these sulfoniums are promising leads for a new type of anti-diabetic agents.
在典型的2型糖尿病小鼠模型KK-Ay小鼠体内评估了中华五层龙茎热水提取物（SCE）的抗糖尿病作用。给KK-Ay小鼠喂食含0.25%和/或0.50% SCE的CE-2日粮三周，可显著抑制血糖和糖化血红蛋白（HbA1c）水平的升高，而体重或食物摄入量无显著变化。给KK-Ay小鼠喂食含0.12% SCE的AIN93M纯化日粮27天，可改善葡萄糖耐量。当用SCE给予将所有可消化糖类都替换为葡萄糖的AIN93M/Glc日粮时，未观察到对HbA1c水平的抑制作用。因此，体外研究认可的作为SCE抗糖尿病作用机制的α-葡萄糖苷酶抑制活性在体内研究中也得到了再次证实。通过使用人α-葡萄糖苷酶评估活性成分沙拉醇（1）、科他醇（3）和新科他醇（4）的α-葡萄糖苷酶抑制活性，发现这些化合物对其抑制作用与对大鼠小肠α-葡萄糖苷酶的抑制作用一样有效（麦芽糖酶的IC50 = 3.9 - 4.9 μM）。主要的锍成分（1 - 4）在人工胃液中高度稳定。此外，在使用原位大鼠结扎肠袢模型的实验中，1 - 4几乎不被肠道吸收。结果表明，这些锍化合物有望成为新型抗糖尿病药物的先导物。
