ARTICLE IN PRESS

Clinical Nutrition (2003) 22(6): 561–568

r 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0261-5614(03)00059-1

ORIGINAL ARTICLE

Naringin supplementation lowers plasma lipids and

enhances erythrocyte antioxidant enzyme activities
in hypercholesterolemic subjects
U. J. JUNG,* H. J. KIM,* J. S. LEE,* M. K. LEE,y H. O. KIM,* E. J. PARK,* H. K. KIM,* T. S. JEONG,z M. S. CHOI*
*Department of Food Science and Nutrition, Kyungpook National University, Daegu, South Korea, y Food and Bio-Industry Research
Institute, Kyungpook National University, Daegu, 702-701, South Korea, z Cardiovascular Research Laboratory, Korea Research Institute of
Bioscience and Biotechnology, P.O. Box115,Yusong, Daejon 305-600, South Korea (Correspondence to : MSC, Department of Food
Science and Nutrition, Kyungpook National University,1370 Sank-Yuk Dong Puk-Ku, Daegu 702-701, South Korea)

Abstract5 Background and aims: Preliminary studies have shown that naringin has a potent lipid-lowering e¡ect and
antioxidant capacity in high-cholesterol diet fed animals. Accordingly, the present study was conducted to investigate
the e¡ect of naringin on hypercholesterolemic subjects. Methods: A hypercholesterolemic group (n = 30) and healthy
control group (n = 30) were established based on the plasma cholesterol levels in the subjects, then all subjects received
naringin (400 mg/capsule/day) with regular meals for a period of 8 weeks. Results: In the hypercholesterolemic subjects,
naringin supplementation was found to lower the plasma total cholesterol by14% and low-density lipoprotein cholester-
ol concentrations by17%, while the plasma triglyceride and high-density lipoprotein cholesterol concentrations remained
una¡ected. The apolipoprotein B levels in the hypercholesterolemic subjects were signi¢cantly lowered after naringin
treatment, yet no change was observed in the apolipoprotein A-1levels.The erythrocyte superoxide dismutase and cat-
alase activities in the hypercholesterolemic group were signi¢cantly increased, whereas the glutathione peroxidase ac-
tivity and plasma TBARS levels were not di¡erent from the baseline measurements. Meanwhile, naringin
supplementation had no a¡ect on plasma lipids, apolipoproteins, and TBARS levels or antioxidant enzyme activities in
the control group. Conclusions: Therefore, these data suggest that naringin may play an important role in lowering plas-
ma cholesterol and regulating the antioxidant capacity in hypercholesterolemic subjects.
r 2003 Elsevier Science Ltd. All rights reserved.

Key words: naringin; hypercholesterolemia; plasma antiallergic, antiviral, antibacterial, antimutagenic

lipids; antioxidant enzymes
Introduction
Hypercholesterolemia is a risk factor for the develop-
ment of cardiovascular diseases including atherosclero-
sis, myocardial infarction, heart attacks, and cerebral
paralysis (1, 2). The normalization of serum levels of
total cholesterol or low-density lipoprotein cholesterol
(LDL-C) through diet therapy or drug administration
has been shown to decrease the incidence of coronary
heart disease (3, 4). Previous epidemiologic studies
suggested that diets rich in fruit and vegetables
are protective against cardiovascular disease (5).
This beneficial effect would appear to be related to
minor components, particularly flavonoids, which
seemingly inhibit LDL oxidation and platelet aggrega-
tion (6).
Flavonoids, a class of naturally occurring compounds
ubiquitous in the plant kingdom, are dietary phenolic
compounds with biological and pharmacological
properties, such as antioxidant, anti-inflammatory,
and anticarcinogenic activities (7). Among naturally
occurring flavonoids, naringin (40 ,5,7-trihydroxyflavo-
none 7-rhamnoglucoside, C27H32O14, FW: 580.5),
a glycone of naringenin, is a widely distributed
bioflavonoid in grapefruit and citrus fruit peel. Several
previous studies have demonstrated that naringin has
antiviral (8, 9), anticancer (10), and hepatoprotective
effects (11, 12). Naringin has also been reported to have
antioxidant effects, such as the inhibition of lipid
peroxidation in blood cell membranes (13) and free
radical scavenging (14). Recently, several studies (15–18)
have reported that hesperidin, a substance chemically
similar to naringin, can lower the blood cholesterol
level.
Naringin has been tested as a potential agent for
improving the cholesterol metabolism in diet induced
hypercholesterolemic animals (19–22). However,
the physiological functions of naringin have rarely
been investigated in humans. Accordingly, the present
study examined whether naringin can beneficially
alter the plasma cholesterol concentration and
antioxidant capacity in subjects with hypercholestero-
lemia.

561
 ARTICLE IN PRESS
562 NARINGIN SUPPLEMENTATION IN HYPERCHOLESTEROLEMIC SUBJECTS
Subjects and methods
Subjects
Sixty volunteers aged 30–60 years were recruited from
Daegu and its suburbs. Most subjects were office
workers in high schools and universities in the
area. After an initial screening, the subjects were
classified according to their plasma cholesterol levels:
hypercholesterolemic group (n ¼ 30; plasma total cho-
lesterol: 6.1370.14 mmol/l, plasma LDL-cholesterol:
5.4570.24 mmol/l) and healthy control group (n ¼ 30;
plasma total cholesterol: 4.9870.11 mmol/l, plasma
LDL cholesterol: 4.0970.13 mmol/l). Most of the
participants were nonsmokers, and all were free of
thyroid disorders, kidney disease, and diabetes, and had
not been taking cholesterol-lowering medication before
the study.
All subjects received naringin (400 mg/capsule/day)
with regular meals for a period of 8 weeks. Before
entering the study, each subject received instructions
from a dietitian on how to record their food intake. The
food intake was recorded according to the 24-h recall
method and the nutrient intake calculated using the
CAN program developed by the Korean Nutrition
Society. All participants lived independently and were
instructed to maintain routine activities during the
study. Exercise and physical activities were not re-
stricted. The current study protocol was approved by
the Ethics Committee at Kyungpook National Uni-
versity for human study.
Plasma lipids level
A fasting blood sample was taken from each subject
before the onset of the study as a baseline and after
8-week intervention period. The blood samples were
centrifuged at 1000  g for 15 min at 41C to determine
the plasma lipids and apolipoproteins. The total
cholesterol (TC), triglyceride (TG), and HDL-cholester-
ol (HDL-C) were determined based on enzymatic
methods using an ADVIA 1650 (Japan) autoanalyzer
with a Laudox (United Kingdom) kit. The LDL-
cholesterol (LDL-C) was calculated using the Friede-
wald formula. The apolipoprotein (apo) A-1 and B
levels were determined by immunonephelometry using a
cobas Integra APOA cassette (Germany) and cobas
Integra 800 (Germany).
Erythrocyte antioxidant enzyme activities
The preparation of the enzyme source in the erythro-
cytes was as follows. After the EDTA treated blood
samples were centrifuged at 1000  g for 15 min at 41C,
the plasma and buffy coat were discarded. The
separated erythrocytes were then washed with a 0.9%
NaCl solution three times. The washed cells were lysed
in an equal volume of distilled water and mixed
thoroughly. The hemoglobin concentration was then
estimated in aliquot of this hemolysate using a
commercial assay kit (No. 525-A, Sigma Chemical
Co.). Next, an appropriately diluted hemolysate were
prepared from the erythrocyte suspension by the
addition of distilled water to estimate the catalase
(CAT) and glutathione peroxidase (GSH-Px) activities.
Furthermore, to remove the hemoglobin by precipita-
tion with ethanol:chloroform (23), 0.4 ml of an etha-
nol:choloroform (3:5, v/v) mixture was added to an
aliquot (1 ml) of the hemolysate cooled in ice. This
mixture was stirred constantly for 15 min, then diluted
with 0.2 ml of distilled water. After centrifugation for
10 min at 1600  g, the pale yellow supernatant was
separated from the protein precipitate and used to assay
for superoxide dismutase (SOD).
The SOD activity was measured according to the
method of Marklund and Marklund (24) with a slight
modification. One hundred microliters of the solution
was mixed with 1.5 ml of a Tris–EDTA–HCl buffer (pH
8.5), then 100 ml of 15 mM pyrogallol was added and the
reaction mixture incubated at 251C for 10 min. The
reaction was terminated by adding 50 ml of 1 N HCl,
then the activity was measured at 420 nm. One unit was
determined as the amount of enzyme that inhibited the
oxidation of pyrogallol by 50%. The activity was
expressed as unit/g hemoglobin.
The CAT activity was measured using Aebi’s (25)
method with a slight modification. Ten microliters of the
solution was added to a cuvette containing 2.89 ml of a
50 mM potassium phosphate buffer (pH 7.4), then the
reaction was initiated by adding 0.1 ml of 30 mM H2O2
to make a final volume of 3.0 ml at 251C. The
decomposition rate of H2O2 was measured at 240 nm
for 5 min using a spectrophotometer. A molar extinction
coefficient of 0.041 (mM)1 cm1 was used to determine
the CAT activity. The activity was defined as the
decreased mmol H2O2/min/g hemoglobin.
The GSH-Px activity was measured using Paglia and
Valentine’s (26) method with a slight modification. The
reaction mixture contained 2.525 ml of a 0.1 M of Tris–
HCl (pH 7.2) buffer, 75 ml of 30 mM glutathione, 100 ml
of 6 mM NADPH, and 100 ml of glutathione reductase
(0.24 unit). One hundred microliters of the solution was
added to 2.8 ml of the reaction mixture and incubated at
251C for 5 min. The reaction was initiated by adding
100 ml of 30 mM H2O2 and the absorbance measured at
340 nm for 5 min. A molar extinction coefficient of
6.22 (mM)1 cm1 was used to determine the activity.
The activity was expressed as the oxidized mmol
NADPH/min/g hemoglobin.
Plasma lipid peroxidation (TBARS assay)
As a marker of lipid peroxide production, the plasma
TBARS (thiobarbituric acid-reactive substances) con-
centration was measured using the method of Tarlard-
giseral (27). Briefly, 500 ml of plasma was well mixed
 ARTICLE IN PRESS
CLINICAL NUTRITION 563

with 3 ml of 5% trichloroacetic acid and 1 ml of freshly
prepared 60 mM thiobarbituric acid (TBA). After
incubation at 801C for 90 min, the samples were cooled
at room temperature and centrifuged at 1000  g for
15 min at 41C, then the absorbance of the supernatant
was measured at 535 nm using tetramethoxy propane
(Sigma Chemical Co.) as the standard.
Statistical analysis
All data are presented as the mean7S.E. The data were
assessed by a Student’s t-test performed using the
statistical package from the Social Science Software
(SPSS) program. Statistical significance was considered
at Po0.05.
Results
Subject characteristics and food intake profiles
The subjects’ baseline characteristics and nutrient
intakes during the experimental period are presented
in Tables 1 and 2, respectively. The mean ages of the
hypercholesterolemic subjects and control subjects were
49.8179.74 and 45.8671.64 years, respectively. There
were no significant differences in body weight, height,
body mass index (BMI), waist/hip circumference ratio
Table 1 Comparison of characteristics at study entry
Control (n ¼ 30)
Age (year) 45.8671.64
Body Weight (kg) 61.53712.61
Height (cm) 163.5774.79
BMI (kg/m2) 22.8271.31
WHR 0.8370.03
(WHR) at the baseline (Table 1). Analysis of the
participants’ 3-day food records during the test period
indicated no significant differences in energy and
nutritient intakes between the groups (Table 2). The
energy composition of the diet included: 50–60% from
carbohydrates; 15–20% from proteins; 20–25% from
fat. The cholesterol intake was less than 300 mg/day.
The intake of carbohydrates, fat, cholesterol, Ca, Vit B1,
Vit B2, Vit C tended to be slightly higher in the control
group than in the HC group.
Plasma lipid levels
The changes in the plasma total cholesterol and
triglyceride concentrations are shown in Figure 1 for
both groups. In the HC group, the plasma total
cholesterol concentration was significantly lowered from
6.1370.14 mmol/l at the start to 5.2670.31 mmol/l at
the end of the study, while the triglyceride concentration
only changed slightly from 1.9670.24 to 1.697
0.16 mmol/l after the treatment. However, no significant
changes in plasma total cholesterol and triglyceride
concentrations were observed in the control group. As
shown in Figure 2, the plasma LDL-cholesterol con-
centration in the HC group was also significantly
lowered from 5.4570.17 to 4.5370.25 mmol/l after
naringin treatment, whereas the control group showed
no significant change between pre- and post-treatment.
Neither group displayed any significant change in the
HC (n ¼ 30) plasma HDL-cholesterol concentration from the base-
49.8179.74
64.17722.34
167.2378.39
24.7670.62 Before After
0.8870.01
Plasma TC (mmol/L)

7.0
Values are mean7S.E. HC: hypercholesterolemic subjects; BMI: body 6.0
mass index; WHR: waist/hip circumference ratio. 5.0
4.0
3.0
2.0
Table 2 Energy and nutrient intakes of subjects during experimental 1.0
period 0.0
Control HC
Control (n ¼ 30) HC (n ¼ 30) (a)
Energy (kcal) 1725.977222.73 1778.52771.33 Before After
Protein (g) 72.2478.08 73.4374.47
Fat (g) 41.6776.69 39.9273.33 2.0
Plasma TG (mmol/L)

Carbohydrate (g) 260.34730.33 247.4279.72

Fiber (g) 5.3670.80 6.1870.61
Ca (mg) 488.66761.91 471.63748.13 1.5
Fe (mg) 11.1071.60 12.1870.80
Na (mg) 4450.867477.67 4629.617366.69 1.0
Vitamin A (R.E) 663.667113.42 731.297122.36
Vitamin B1 (mg) 1.2070.22 1.0770.08 0.5
Vitamin B2 (mg) 1.0770.19 1.0270.11
Vitamin C (mg) 132.53756.75 108.08713.94 0.0
Niacin (mg) 15.9072.58 17.6271.16 (b) Control HC
Cholesterol (mg) 199.33719.70 188.20711.48
% Calories from carbohydrates 60.7971.34 56.6172.23 Fig. 1 Effect of naringin administration on plasma total cholesterol
% Calories from protein 17.0570.77 16.5870.78 (TC) and triglyceride (TG) concentrations in control and hyper-
% Calories from fat 21.4971.08 20.0871.30 cholesterolemic (HC) group. Values are mean7S.E. #Values are
significantly different between HC and control group by Student’s t-
Values are mean7S.E. Values were derived from 3-day dietary food test at Po0.05. *Values are significantly different between before and
records. HC: hypercholesterolemic subjects. after naringin treatment within group by Student’s t-test at Po0.05.
 ARTICLE IN PRESS
564 NARINGIN SUPPLEMENTATION IN HYPERCHOLESTEROLEMIC SUBJECTS

line. At the baseline, the plasma HDL-C/TC (%) in the TBARS concentrations and antioxidant enzyme activities
HC group was significantly lower than in the control
The activities of the three antioxidant enzymes SOD,
group (Table 3). However, after treatment with nar-
CAT, and GSH-Px in erythrocyte are shown in Table 5.
ingin, the HDL-C/TC (%) increased significantly
The erythrocyte SOD and CAT activities in the HC
in the HC group compared with the value before
group were significantly increased, whereas these activ-
treatment, while no change was observed in the control
ities in the control group were only slightly higher after
group (Table 3). The apolipoprotein levels are shown in
naringin treatment. The naringin treatment had no
Table 4. Before naringin treatment, the apo B
affect on the erythrocyte GSH-Px activities in either
concentration was significantly higher in the HC group
group. The plasma lipid peroxide concentrations were
than in the control group, however, after naringin
determined by measuring the TBARS concentration
supplementation for 8 weeks the HC group displayed
(Table 5). The plasma TBARS concentration in both
significantly lower apo B levels, yet, no change in the
groups tended to be lower, yet not significantly different
apo A-1 levels. The control group exhibited no
from the baseline by naringin treatment.
significant differences in the apo A-1 and apo B levels
after naringin treatment.

Discussion

Before After There is increasing evidence to support the protective

6 #
5 **
LDL-C (mmol/L)
effects of antioxidants in a variety of pathological
conditions, such as cardiovascular disease (28–34).
Furthermore, various clinical studies have suggested

that lowering the blood cholesterol has a significant

4
effect on preventing and inhibiting the progression of
3 atherosclerosis (35–39). Flavonoids are widely recog-
nized as naturally occurring antioxidants that contribute
2
to cardioprotective action. Naringin is a citrus flavonoid
1 present in grapefruit and citrus fruits and there have
been several previous reports on its antioxidant effects
0 and cholesterol-lowering potential. Our previous study
Control HC showed potent cholesterol-lowering effect and anti-
Fig. 2 Effect of naringin administration on plasma low-density oxidant capacity of naringin in various animal models
lipoprotein cholesterol (LDL-C) concentrations in control and (19–22). In the current study, the effects of naringin on
hypercholesterolemic (HC) group. Values are mean7S.E. #Values the plasma lipid profiles and antioxidant enzyme acti-
are significantly different between HC and control group by Student’s
t-test at Po0.05. **Values are significantly different between before vities were examined in hypercholesterolemic subjects
and after naringin treatment within group by Student’s t-test at compared to healthy control subjects.
Po0.01.

Table 3 Effect of naringin administration on plasma HDL-C concentration, HDL-C/TC (%), and atherogenic index in HC and control subjects
Control (n ¼ 30) HC (n ¼ 30)
Before After Before After
HDL-C (mmol/l) 1.3670.06 1.4870.15 1.4070.09 1.4070.09
HDL-C/TC(%) 27.3071.44 28.5175.09 22.0471.26n 26.9071.76y
Atherogenic Index 2.6170.19 2.4570.43 3.3770.22n 2.7370.26
n
Values are significantly different between HC and control group by Student’s t-test at Po0.05.
y
Values are significantly different between before and after naringin treatment within group by Student’s t-test at Po0.05.
Values are mean7S.E. HC: hypercholesterolemic subjects; Atherogenic Index: [(TC-HDL-C)/HDL-C].

Table 4 Effect of naringin administration on plasma apo A-1 and apo B levels in HC and control subjects
Control (n ¼ 30) HC (n ¼ 30)
Before After Before After
Apo A-1 (mg/dl) 150.8677.45 142.0076.93 139.0076.10 134.4675.25
Apo B (mg/dl) 103.6374.79 92.7573.05 123.0075.23n 102.2373.73y
n
Values are significantly different between HC and control group by Student’s t-test at Po0.05.
y
Values are significantly different between before and after naringin treatment within group by Student’s t-test at Po0.005.
Values are mean7S.E. HC: hypercholesterolemic subjects; Apo A-1: apolipoprotein A-1; Apo B: apolipoprotein B.
 ARTICLE IN PRESS
Table 5 Effect of naringin administration on erythrocyte antioxidant enzyme activities and plasma TBARS in HC and control subjects
Control (n ¼ 30)
Before
SOD (unit/g Hg) 191.5877.01
CAT (mmol /min/g Hg) 199.32716.10
GSH-Px (mmol/min/g Hg) 49.9372.43
TBARS (nmol/ml) 1.9370.09
n
Values are significantly different between before and after naringin treatment within group by Student’s t-test at Po0.05.
Values are mean7S.E. Hg: hemoglobin.
Although flavonoids in plants are common compo-
nents of the human diet, an estimation of the total
flavonoid intake is difficult because limited data on food
contents are available. Earlier studies in the United
States estimated that the daily intake of flavonoids was
about 1 g/day when expressed as glycosides, or 650 mg/
day when expressed as aglycones (40). However, other
studies have also estimated that the human intake of all
flavonoids is 23 B a few hundreds of milligram per day
(41, 42). In addition, there is currently little of informa-
tion concerning the amount of flavonoids that are
needed on acute or chronic basis to trigger the positive
health effects. Based on limited data, approximately
150 mg of flavonoids is needed to observe an acute
effect and 500 mg for chronic effect (43). Recently,
human studies have not shown any adverse effects
associated with oral administration of quercetin, the
major flavonol in human food, in a single dose of up to
4 g (44) or after taking 500 mg dose twice daily for one
month (45). Like most flavonoids, naringin has
been empirically proven to have no side-effects, as
historically humankind has been ingesting citrus fruits
for a long time (46). The lipid-lowering effect and
hepatoprotective action was demonstrated with
naringin 500 mg/kg/day for 8 weeks in hypercholester-
olemic rabbits (46). Accordingly, we used the dose
of naringin (400 mg/day) based on the other’s findings
(43–46).
This study showed, in the hypercholesterolemic
subjects, that consumption of naringin 400 mg/day for
8 weeks significantly improved the plasma lipid profile
by reducing the plasma total cholesterol and LDL-
cholesterol, and by increasing the HDL-C/TC (%). The
increase in the HDL-C/TC (%) was entirely due to the
decrease in the total cholesterol. This result is also
supported by previous studies (19–22), in which the
supplementation of a citrus flavonoid mixture or
naringin was shown to lower the plasma cholesterol
concentration in rats or rabbits fed a high-cholesterol
diet. Citrus juices have also been found to induce the
reduction of LDL-cholesterol in hypercholesterolemic
rabbits (47). In the current study, the plasma cholesterol
lowering effect due to naringin treatment was only
significant in the hypercholesterolemic subjects. This
corresponds with Harats’ results, where no changes in
the plasma lipids were found in normocholesterolemic
subjects given orange juice (48).
CLINICAL NUTRITION 565
HC (n ¼ 30)
After Before After
199.40710.57 198.9078.06 221.4975.59n
215.69718.18 186.1076.51 216.4378.88n
39.4675.57 51.2672.22 46.6873.45
1.8470.13 1.9870.10 1.7770.07
Apo B, a major component of LDL-cholesterol,
serves as the principal carrier of lipids to peripheral
tissue (49, 50). Apo B levels are strongly correlated with
the LDL-cholesterol concentration and have a higher
specificity as a screening test for identifying individuals
with an elevated LDL-cholesterol concentration than
total cholesterol concentration (51). In the hypercholes-
terolemic subjects, in addition to a reduction in the
plasma LDL-cholesterol concentration, the apo B levels
were also significantly decreased after naringin treat-
ment. Kurowska (52) noted similar results in HepG2
cells by using citrus juices containing high concentra-
tions of limonoids.
Although the lipid-lowering mechanism of naringin
has not been established in human subjects, our previous
animal studies (19–22) indicated that naringin had an
inhibitory effect on hepatic HMG-CoA reductase and
acyl CoA:cholesterol acyltransferase that are a rate-
limiting enzyme of the cholesterol biosynthetic pathway
and a cholesterol esterifying enzyme, respectively.
Several studies (53, 54) suggested that phytoestrogens
such as flavonoid could contribute to the cholesterol-
lowering effect, especially of postmenopausal woman
since they have a weak estrogenic activity. The
physiological effect of isoflavones is likely partially
related to direct interaction with or binding to estrogen
receptors (55, 56). Among isoflavones, genistein and
diadzein that are potent phytoestrogens lowered plasma
cholesterol concentrations in subjects with initially
elevated levels, but had little effect in subjects with
normal cholesterol concentrations (53, 57). These results
were also found in the present study, where naringin had
a cholesterol-lowering effect in hypercholesterolemic
subjects compared to the healthy control subjects.
However, naringenin, aglycone of naringin and an
isomer of genestein, exhibited low or no estrogenic
activity (58). Thus, the effect of the estrogenic activity of
naringin remains to be established and the potential
beneficial effects of phytoestrogen in the prevention of
cardiovascular disease should be further investigated.
Kroyer (59) demonstrated that the antioxidant effects
of hesperidin and naringin and their aglycones are
responsible for their antioxidant activity of citrus peel.
Naringin also exhibit a chemopreventive effect against
the pro-oxidant activated by p41A2 (60). Other studies
have reported that naringin can slightly inhibit lipid
peroxidation in rats (61) and has an inhibitory effect
 ARTICLE IN PRESS
566 NARINGIN SUPPLEMENTATION IN HYPERCHOLESTEROLEMIC SUBJECTS
against cytochrome P450 (CYP3A) activity in human
liver microsomes (62, 63). In addition, citrus fruit
supplementation has beneficial effects on lipoprotein
oxidation in young men with a diet high in saturated fat
(64). On the other hand, flavonoids containing phenol B
rings, such as naringin or naringenin (flavanone contain-
ing a phenol B ring), hesperetin, and apigenin (flavone
containing a phenol B ring) have all been implicated in
the initiation of atherosclerosis and carcinogenesis
because of their involvement in oxygen activation and
oxidative destruction by other pheroxyl radicals (65).
These flavonoids can act as independent pro-oxidants in
transition metal catalyzed autoxidation reactions (66).
Ratty (67) also showed that naringin promotes ascorbic
acid induced lipid peroxidation and that flavonoid
glycones, such as naringin and hesperidin, are much
less potent in their antiperoxidative capacity than their
corresponding aglycones. However, the evidences for
pro-oxidant action of flavonoids, so far, has come
primarily for studies done in vitro.
Naringin supplementation, in the present study, did
result in a dramatic increase in the SOD and CAT
activities in the hypercholesterolemic subjects compared
to the control subjects, although GSH-Px activity was
unaffected. Similar changes were also found in high-
cholesterol fed rabbits (22), where naringin markedly
increased the hepatic SOD and CAT activities, yet had
no effect on the hepatic GSH-Px activity. SOD plays an
important role in protecting cells from oxidative damage
by converting superoxide radicals into hydrogen per-
oxide, which is then further metabolized by CAT and
GSH-Px, where CAT detoxifies hydrogen peroxide and
GSH-Px catalyses the destruction of hydrogen peroxide
and lipid hydroperoxides. As such, an elevated CAT
and/or GSH-Px activity should follow if a beneficial
effect from an increase in SOD activity is to be expected
(68). Therefore, the increased SOD and CAT activities
in the erythrocyte from hypercholesterolemic subjects
may represent an increased cell membranes defense
against oxygen and lipid free radicals, thereby protecting
the organisms from pro-oxidants in the erythrocyte. The
plasma TBARS concentration in both hypercholester-
olemic and control subjects tended to be lower by
10.61% and 5.15%, respectively, yet not significantly
different from the baseline. No difference in the TBARS
level could indicate that the naringin did not function as
a prooxidant in the erythrocyte of these hypercholester-
olemic subjects. We previously found that the low dose
naringin (0.05%, w/w) or naringenin (0.02%, w/w) was
very effective on plasma cholesterol-lowering, but not
on altering the plasma TBARS level in high-cholesterol
diet fed rabbits or rats (22, 69).
In conclusion, the present study suggests that naringin
consumption is beneficial for lowering the plasma total
cholesterol and LDL-cholesterol concentration in hy-
percholesterolemic subjects. In addition, naringin sup-
plementation in hypercholesterolemic subjects improved
the antioxidant system by increasing the SOD and CAT
activities, although for some unknown reason there was
no significant effect on the plasma TBARS concentra-
tion. Accordingly, it would appear that naringin, a
naturally occurring antioxidant, is effective in lowering
plasma cholesterol and altering a part of the antioxidant
status. Further studies are required to determine the
dose-related changes of naringin and its possible use as a
putative hypocholesterolemic drug.
Acknowledgements
This study was supported by a grant of the Korea Health 21 R&D
Project, Ministry of Health & Welfare, Republic of Korea (02-PJ1-
PG3-22000-0042).
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