The membrane-bound enzyme ACAT (acyl-CoA: cholesterol acyltransferase) in the intestinal mucosa plays an important role in the absorption of cholesterol. Refined Rice Kefiran showed a concentration-dependent inhibition of ACAT in the gut tract of rabbits.
It was speculated that the serum lipid metabolism was improved by kefiran-inhibition of the esterification of cholesterol and the repression of the absorption of cholesterol in the intestinal mucosa. Furthermore, we investigated the action that increases cholesterol-excretion by refined Rice Kefiran and Rice Kefiran using rats in two experimental systems, i.e., cholesterol loading and orotic acid-administration. In the cholesterol loading test, the dry faecal weight increased in the Rice Kefiran group by 1.5% during the stool collection. The excretion amount and excretion rate of total cholesterol, bile acid, and total sterol showed higher values in both of the experimental groups than the control group, and the 3% Rice Kefiran group had a significant increase. These results suggested that a part of the mechanism of the physiological activity expressed by kefiran was caused by the adsorption removal action of intestinal tract circulatory cholesterol in the intestinal tract lumen.
The increase of bile acid was assumed to be caused by the absorption inhibition of dietary cholesteric acid. The effect on the intestinal tract circulatory sterol was strongly suggested by the improvement action for the endogenous sterol increase by orotic acid.
■Absorption inhibition action of cholesterol by refined Rice Kefiran to
intestinal tract ACAT in rabbits
|
Group
|
Concentration (mg/mL)
|
Rate of inhibition (%)
|
IC50
|
Ki
|
pKi
|
|
Refined Rice Kefiran
|
6.00
|
65
|
4.1mg/ml
|
2.3×10-6M
|
5.63
|
|
3.00
|
40
|
|
2.00
|
43
|
|
0.60
|
11
|
|
0.20
|
0
|
|
0.06
|
0
|
|
0.02
|
0
|
|
Lovastatin
|
----
|
14.1μM
|
1.4×10-5M
|
4.90
|
The molar concentration was estimated with the average molecular weight of 1,750,000. pKi = antilogarithm of Ki, Lovastatin was used for the positive control.
■Rice Kefiran actions that promote the excretion in cholesterol-loading rats
|
Control group 1.5% Rice Kefiran group 3.0% Rice Kefiran group
|
Dry faecal weight 1.65±0.049a 1.84±0.066b 1.77±0.056ab
(g/rat/day)
|
Faecal total cholesterol 0.482±0.045a 0.576±0.072ab 0.599±0.016b
(mmol/rat/day)
|
Faecal total cholesterol 16.3± 1.42 19.2± 2.55 19.7± 1.12
excretion rate (%)
|
Faecal bile acid 0.154±0.033a 0.181±0.026ab 0.216±0.019b
(mmol/rat/day)
|
Faecal bile acid 96.6± 8.2a 112± 16.8ab 131± 10.3b
excretion (%)
|
Faecal total sterol 0.637±0.049a 0.757±0.076ab 0.815±0.022b
(mmol/rat/day)
|
Data are expressed as mean ± standard error (n=6). a,bValues with different superscriptions are significantly different (p < 0.05).
|
