Salacinol and Related Analogs: New Leads for Type 2 Diabetes Therapeutic Candidates from the Thai Traditional Natural Medicine Salacia chinensis

Abstract

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.

Aromatase Inhibitory Activity of Geranylated Coumarins, Mammeasins C and D, Isolated from the Flowers of <i>Mammea siamensis</i>

“…[1][2][3][4][5][6][7][8][9][10] Several coumarins, [1][2][3][4][5][6][7] xanthones, 8,9) triterpenoids, 10) and steroids 10) have been isolated from the flowers, 1,2,6,7,10) seeds, 3,9) twigs, 4,8) and bark 5) of this plant. In the course of our characterization studies on bioactive constituents in Thai natural medicine, 1,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] we reported that the methanol extract of the flowers of M. siamensis and its coumarin constituents showed inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW264.7 cells.…”

“…In the course of our characterization studies on bioactive constituents in Thai natural medicine, 1,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] we reported that the methanol extract of the flowers of M. siamensis and its coumarin constituents showed inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW264.7 cells. 1) Further studies revealed that the methanol extract inhibited enzymatic activity against aromatase.…”

Aspects of extraction and biological evaluation of naturally occurring sugar-mimicking sulfonium-ion and their synthetic analogues as potent α-glucosidase inhibitors from Salacia: a review

“…Thus, it is clear that the stereochemistry at the different stereogenic centers on the side chain plays a signicant role in biological activity. It appears that the compounds containing the S conguration at C-2 0 , the R conguration at C-4 0 , and the S conguration at C-5 0 are the most active in the sulfur series of compounds; however, that in the selenium series the activities of the selenium analogues, (52) and (53), suggest that the stereochemistry at C-5 0 could be R. The stereochemistry at C-3 0 was judged to be unimportant but can be xed as S to reect a presumed common biosynthetic pathway as salacinol. However, the overall conclusion was that the effect of the acyclic chain extension did not confer any dramatic change on inhibitory properties for this particular enzyme, because the K i values of the active chain-extended analogues were in a similar range to those of salacinol (5) (0.19 mM) and blintol (16) (0.49 mM).…”

A Review of Biologically Active Natural Products from a Desert Plant <i>Cistanche tubulosa</i>

“…Therefore improving postprandial hyperglycemia may form part of the strategy for the prevention and management of cardiovascular disease in diabetes. 136) We previously reported that several antidiabetogenic therapeutic candidates were obtained from natural resources such as Kochia scoparia, 137) Borassus flabellifer, 138) Solanum lycocarpum, 139) Sinocrassula indica, 140) Shorea roxburghii, 141) Helichrysum arenarium, 142) and Salacia reticulata, S. oblonga, and S. chinensis [143][144][145][146][147][148] evaluated by postprandial hyperglycemia in sugar-loaded rats and/or mice models. In these experiments the effects of the principal phenylethanoid glycosides from the stems of C. tubulosa, echinacoside (28) and acteoside (29), on postprandial increase in blood glucose levels in starch-loaded mice were examined.…”