Biochemical studies on the antilithogenic effect of dietary fenugreek seeds (Trigonella foenum-graecum)

Cholesterol gallstone (CGS) disease ─ one of the major contemporary health problems,
is a highly prevalent gastroenteronological disorder resulting from alteration in hepatic and
biliary cholesterol homeostasis. The prevalence of this disease is very high in Europe and
USA (10-15% of population), lesser in Asia (3-15%) and very low (< 5%) in Africa. The
pathophysiology of CGS involves alteration in the delicate equilibrium between the three
lipid components of bile, viz., cholesterol, bile acids and phospholipids. Increase in the
concentration of cholesterol or decrease in the concentration of phospholipids and bile
acids would push the CSI towards crystallization.
Fenugreek seed has been documented to have hypocholesterolemic property, which is
mainly attributable to the intrinsic dietary fiber constituent. The other constituents of
fenugreek having the hypocholesterolemic property include saponins, diosgenin,
trigonelline and 4-hydroxyisoleucine. With the aim of extending our knowledge on the
possible anti-lithogenic influence of dietary fenugreek seeds mediated through
hypocholesterolemic effect, the present research programme envisaged. Animal studies
were carried out to study the effect of dietary fenugreek seeds on the induction of CGS,
regression of pre-established CGS, effect on biliary proteins and also its combination with
another known hypocholesterolemic spice onion on the incidence and severity of CGS.
The antilithogenic potential of fenugreek seeds was evaluated at different dietary doses
both in their raw and heat processed forms during HCD induced CGS formation in mice.
CGS was induced were induced by feeding lithogenic diet (0.5% cholesterol and 0.25%
bile salts) for 10 weeks. Fenugreek seed powder was included at 5, 10 and 15% of this
lithogenic diet. Dietary fenugreek significantly lowered the incidence of CGS; the
incidence was 63, 40 and 10% in 5, 10 and 15% fenugreek group respectively, as
compared to 100% in lithogenic control. Serum cholesterol level was decreased by 26–
31%, hepatic cholesterol was lowered by 47–64%. Biliary cholesterol was reduced to
8.73–11.2 mM with dietary fenugreek from 33.6 mM (HCD) and CSI was reduced to
0.77–0.99 with fenugreek addition as compared to 2.57 in HCD group.
Abstract
CGS was induced by feeding a HCD for a period of 10 weeks. After the CGS
induction, groups of these animals were maintained for further 10 weeks on high
cholesterol/ basal control diet/ 6% fenugreek powder / 12% fenugreek powder diets.
Dietary fenugreek significantly lowered incidence of CGS, the extent of regression being
61 and 64% in the lower and higher dose groups when compared to 10% regression in
basal control group. Serum cholesterol reduced by 35%, hepatic cholesterol decrease by
53-63%, also decreased C: P ratio (0.40 - 0.44 as compared to 0.79 in the basal control
group). Biliary C: BA ratio lowered by 67 and 73%. The CSI was 0.90 and 0.42 as
compared to 1.86 in the basal control diet group). Activities of liver functioning enzymes
in serum increased with HCD feeding and this effect was countered by fenugreek feeding.
Fenugreek addition reduced hepatic lipid peroxides, increased antioxidant molecules and
activities of hepatic antioxidant enzymes ─ glutathione reductase, glutathione-Stransferase
and glutathione peroxidase compared to HCD.
Incorporation of fenugreek into HCD decreased the cholesterol content (70.5%), total
protein (58.3%), glycoprotein (27.5%), lipid peroxides (13.6%) and CSI (from 1.98 to
0.75), increased the bile flow rate (19.5%), prolonged the cholesterol NT, reduced the
vesicular form of cholesterol (65%), increased smaller vesicular form (94%), increased
phospholipid (33%) and total bile acid (49%) in HCD + fenugreek group as compared to
HCD group. Electrophoretic separation of LMW proteins showed the presence of high
concentration of 28 kDa protein which might be responsible for the prolongation of
cholesterol NT in the fenugreek fed groups.
The results of the effect of combination of fenugreek seeds and onion showed that
fenugreek and onion individually exerted antilithogenic effect, the effect was higher in the
case of fenugreek seeds but the combination was not more than that of fenugreek seeds
alone.
The present study has evidenced the antilithogenic potency of fenugreek seeds is
attributable to its hypocholesterolemic effect. Fenugreek not only reduced incidence, but
also regressed the existing CGS, thus preventing possible recurrence. The antilithogenicity
of the fenugreek was considered to be due not merely to their ability to lower
CSI, but also to their influence on biliary proteins. Among the studied spices fenugreek
showed better antilithogenic effect.