Salacinol and related analogs: New leads for type 2 diabetes therapeutic candidates from the Thai traditional natural medicine Salacia chinensis

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Abstract

© 2015 by the authors. The antidiabetic effect of a hot water extract of stems of Salacia chinensis (SCE) was evaluated in vivo in KK-A y 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-A y 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-A y 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 (IC 50 = 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.

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Morikawa, T., Akaki, J., Ninomiya, K., Kinouchi, E., Tanabe, G., Pongpiriyadacha, Y., … Muraoka, O. (2015). Salacinol and related analogs: New leads for type 2 diabetes therapeutic candidates from the Thai traditional natural medicine Salacia chinensis. Nutrients, 7(3), 1480–1493. https://doi.org/10.3390/nu7031480

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