Abstract
The predominantly beta-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys. Cynomolgus macaques (Macaca fascicularis) were fed, during two 3-week periods, a semipurified diet with 0.1% cholesterol and a similar ration containing 1% DG, respectively. A Chow diet was given for 5 weeks between the experimental periods. Cholesterol and bile acid balance were analyzed during the last week of each semipurified diet. Diosgenin glucoside reduced cholesterolemia from 292 mg/dl to 172 mg/dl, decreased intestinal absorption of exogenous cholesterol from 62.4% to 26.0%, and increased secretion of endogenous cholesterol from -0.8 to 93.5 mg/day. The fecal excretion of neutral steroids rose from 40.7 to 157.3 mg/day; that of bile acids changed, nonsignificantly, from 23.1 to 16.0 mg/day. The cholesterol balance was -44 mg/day in the control period, and 88 mg/day in the DG-fed animals. No toxic signs were observed. Thus, when long-term studies demonstrate that the glucoside is well tolerated, DG and other synthetic glycosides with similar activities may be of use in the management of hypercholesterolemia and atherosclerosis.
Highlights
The predominantly /3-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys
Further studies showed that alfalfa saponins reduce cholesterolemia in the chicken [3, 4], whereas alfalfa prevents hypercholesterolemia and modifies atherogenesis in cholesterol-fed rabbits [5, 6]; Kritchevsky, Teplor, and Story [7] suggested an involvement of alfalfa saponins in reducing cholesterol absorption
We demonstrated that an extract of alfalfa meal, operationally termed alfalfa saponins [16], lowers intestinal absorption of cholesterol in rats [17] and monkeys [18]
Summary
The predominantly /3-anomer of diosgenin glucoside (DG) was synthesized and its effects on cholesterol homeostasis were tested in monkeys. The reduced intestinal cholesterol absorption is not observed with saponin-free alfalfa meal [19]. Alfalfa saponins reduce the hypercholesterolemia expected in monkeys as a result of high-fat, high-cholesterol diets [18, 20, 21], increase the fecal excretion of neutral steroids and probably bile acids [18], prevent atherosclerosis in rabbits [22], and induce the regression of aortic and coronary atherosclerosis in monkeys without any signs of toxicity [21]. Four members of a series of glycosides synthesized in our laboratory, namely diosgenin glucoside (DG), diosgenin cellobioside (DC), tigogenin glucoside (E)a,nd tigogenin cellobioside (TC),decrease the intestinal absorption of cholesterol in rats more effectively, on a weight basis, than do alfalfa saponins; comparable doses of the aglycones diosgenin and tigogenin are ineffective [25], diosgenin at higher doses prevents intestinal absorption of cholesterol in rats [26, 27]. We report here the effects of DG on cholesterol and bile acid balance in cynomolgus macaques
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