British Journal of Nutrition (2012), 108, 603–610 doi:10.

1017/S0007114511006015
q The Authors 2011

Effects of soya oligosaccharides and soya oligopeptides on lipid

metabolism in hyperlipidaemic rats

Shali Xie1,2, Jundong Zhu3*, Yanqi Zhang4, Kai Shi2, Yuangang Shi3 and Xiao Ma1*
1
West China School of Public Health, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, Sichuan 610041,
People’s Republic of China
2
Department of Health Education and Medical Humanities, College of Humanities and Social Sciences, Third Military
Medical University, No. 30 Gaotanyan Road, Chongqing 400038, People’s Republic of China
3
Department of Nutrition and Food Hygiene, College of Military Preventive Medicine, Third Military Medical University,
No. 30 Gaotanyan Road, Chongqing 400038, People’s Republic of China
4
Department of Health Statistics, College of Military Preventive Medicine, Third Military Medical University,
No. 30 Gaotanyan Road, Chongqing 400038, People’s Republic of China
(Submitted 11 April 2011 – Final revision received 3 October 2011 – Accepted 8 October 2011 – First published online 15 November 2011)
British Journal of Nutrition

Abstract
In the present study, we aimed to examine the effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on blood lipid levels,
release of vasoactive substances, antioxidant activity and faecal bile acid (FBA) excretion in rats fed a high-fat diet (HFD). Male Sprague –
Dawley rats were evenly divided into five groups according to diets as follows: regular diet (control), HFD, HFD enriched with 2 % of SOS
(SOS), HFD enriched with 3 % of SOP (SOP) and HFD enriched with 2 % SOS and 3 % SOP (SOSP). The results showed that SOS and SOP
significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, whereas HDL-cholesterol concentration was significantly
increased. Furthermore, SOS and SOP reduced plasma apoB, apoE and the apoB:apoAI ratio, whereas apoAI was significantly increased.
Moreover, SOS and SOP also reduced plasma thromboxane A2 (TXA2) and the TXA2:prostacyclin (PGI2) ratio, whereas plasma PGI2 and
nitric oxide were significantly increased. In addition, SOS and SOP significantly reduced serum and liver malondialdehyde concentrations
and increased FBA excretion. However, we did not observe obvious influences of SOS and SOP on superoxide dismutase activities in the
liver of HFD-fed rats. The combination of 2 % SOS and 3 % SOP showed a more marked effect than SOS or SOP alone in improving the lipid
profile, release of vasoactive substances and increasing FBA excretion (P,0·05). In summary, SOS and SOP might help prevent athero-
sclerosis through improving abnormal blood lipid levels, regulating vasoactive substances and protecting against oxidative stress.

Key words: Soya oligosaccharides: Soya oligopeptides: Lipid metabolism: Atherosclerosis

CVD is the leading cause of mortality in the world, accounting of plasma cholesterol is present in the LDL fraction(3). Plasma
for the deaths of seventeen million people each year or LDL-cholesterol (LDL-C) crosses the endothelial barrier and
approximately one-third (29 %) of global deaths annually(1). reaches the vascular subendothelial intima, whereby promot-
CVD prevention is a global public health priority. According ing monocyte/macrophage differentiation. Subsequently,
to the estimation of the WHO, 88 % of the global mortality monocyte-derived macrophages take up cholesterol through
and disease burden from CVD occurs in low- and middle- scavenger receptors and become lipid-laden foam cells(4).
income countries(1). For example, CVD causes over three Steinberg et al.(5) showed that the cholesterol accumulating
million deaths each year in China, and at least 230 million in macrophage-derived foam cells comes from circulating
Chinese are suffering from CVD. The origin of CVD is lipoproteins, mainly from the atherogenic LDL. Therefore,
multifactorial and its pathological basis is atherosclerosis. plasma lipids play a critical role in the initiation and pro-
Hypercholesterolaemia is recognised as a major and indepen- gression of the atherosclerotic lesion(4), and it is essential to
dent risk factor of atherosclerosis and CVD(2). About 60 – 70 % keep blood cholesterol levels in the appropriate range for

Abbreviations: AI, atherosclerosis index; BW, body weight; FBA, faecal bile acid; HDL-C, HDL-cholesterol; HFD, high-fat diet; LDL-C, LDL-cholesterol;
MDA, malondialdehyde; PGI2, prostacyclin; SOD, superoxide dismutase; SOP, soya oligopeptides; SOS, soya oligosaccharides; SOSP, HFD enriched
with 2 % SOS and 3 % SOP; TC, total cholesterol; TXA2, thromboxane A2.

* Corresponding authors: Professor J. Zhu, email zjdnfs@126.com; Professor X. Ma, fax þ86 28 5585080, email huaxihe@gmail.com
 604 S. Xie et al.

the prevention of atherosclerosis and CVD. On the basis of a Military Medical University, and the body weight (BW) ranged
meta-analysis, a 1 % decrease in plasma cholesterol level can from 190 to 210 g. The animals were individually housed in
reduce the risk of CVD up to 3 %(6). metabolic cages in an environment-controlled room (20– 238C
Hypolipidaemic drugs, particularly statins, are the preferred and 40 – 60 % of humidity) under a 12 h light – 12 h dark cycle
treatment for reducing blood cholesterol levels because of with free access to food and water. All animals were fed for 8
their efficacy and safety(7). However, dietary modification is weeks, and BW was monitored biweekly throughout the
the mainstay of treatment of lipid abnormalities and can study. Food intake was measured three times per week. The
have a significant cholesterol-lowering effect(8). animal protocol was approved by the Third Military Medical
Soyabean, as a traditional Chinese food, has been University Institutional Animal Care Committee and conducted
consumed for thousands of years in China due to its beneficial in accordance with the Third Military Medical University
effects on health. Soya contains a variety of phytochemicals guidelines for the care and use of laboratory animals.
with special health functions, such as soya isoflavones, After a week of adaptation, sixty Sprague –Dawley rats were
saponins, phytic acid, sterol and so on. Besides these, soya evenly divided into five groups according to diets as follows:
oligosaccharides (SOS) and soya oligopeptides (SOP) are regular diet (control), HFD, HFD enriched with 2 % of SOS
two types of bioactive substances extracted from soyabean. (SOS), HFD enriched with 3 % of SOP (SOP) and HFD
SOS is the general term for soluble sugars in soyabean, and enriched with 2 % SOS and 3 % SOP (SOSP). The regular
it is mainly composed of stachyose, raffinose and sucrose. diet was composed of the following ingredients (g/100 g
SOP refers to peptides with molecular weights lower than diet): bean cake, 20; wheat starch, 19; maize starch, 15; rice
1000 Da, and it is derived from soya protein by enzyme starch, 20; bran, 15; fishmeal, 5; bone meal, 3; yeast, 1; salt,
hydrolysis. Some reports(9,10) have suggested that both soya
British Journal of Nutrition

1; and cod liver oil, 1. The total protein/carbohydrate/fat con-

protein and SOP have effects on improving the lipid profile tent of the regular diet was approximately 18, 52 and 5 %,
in hypercholesterolaemic subjects, whereas SOP is more effec- respectively. The ingredients of the HFD were as follows:
tive than soya protein. Many studies found that oligosacchar- 10 % lard, 2 % cholesterol, 1 % bile salt and 87 % regular diet.
ides have cholesterol-lowering properties. However, little In the SOS group, HFD was supplemented with 2 % SOS by
information is known about the effect of SOS on lipoprotein replacing 2 g of bran. In the SOP group, HFD was sup-
metabolism in high-cholesterol-fed animals, especially the plemented with 3 % SOP by replacing 3 g of fishmeal. In the
combined effects of SOS and SOP on improving dyslipidae- SOSP group, HFD was supplemented with 2 % SOS and 3 %
mia. It has been shown that probiotics, such as bifidobacteria SOP by replacing 2 g of bran and 3 g of fishmeal, respectively.
and lactobacilli, have beneficial effects on cholesterol metab- Diets of the HFD and experimental groups were iso-energetic
olism in vitro and in vivo (11). Lan et al.(12) reported that SOS and iso-nitrogenic. At the end of the experiment, after over-
is a powerful prebiotic that can increase caecal bifidobacter- night fasting, rats were anaesthetised using pentobarbital
ium and lactobacilli populations in animals and human sub- sodium, and blood samples from the femoral vein were col-
jects. SOP is the necessary and suitable nutrient for the lected in tubes containing EDTA (1·4 g/l) and Trasylol
growth of intestinal bifidobacteria(13). (100 kU/l). Then, plasma was separated for subsequent bio-
In the present study, we aimed to determine whether SOS chemical analysis and stored at 2708C. Immediately after kill-
and/or SOP had significant effects on lipid metabolism in a rat ing the animal, liver tissues were dissected and stored at
model with hyperlipidaemia induced by a high-fat diet (HFD). 2 708C for later antioxidant activity assay. Atherosclerosis
Besides plasma lipid parameters, we examined vasoactive index (AI) was calculated according to the Fridewald formula:
substances, antioxidant activity and faecal bile acid (FBA)
excretion in order to explore the potential application of SOS AI ¼ LDL-C=HDL-C:
and SOP in CVD prevention. The second aim of the study was
to determine whether the combination of SOS and SOP had All faeces were collected for three consecutive days at the
additive or synergistic effects on these parameters. end of the experiment. The collected faeces were stored at
2 208C for later determination of FBA content by phosphomo-
lybdate colorimetry after 16 h of vacuum freeze-drying.
Materials and methods
Materials
SOS extracted from soyabean whey was provided by Shanghai Biochemical analysis
Far-reaching Food Company Limited (Shanghai, China). The
Serum lipid profile analysis. Serum total cholesterol (TC),
total sugar content was $ 70 %.
TAG, LDL-C and HDL-cholesterol (HDL-C) levels were
SOP was provided by Shandong Zhongshi Duqing Biotech
determined by commercial enzymatic test kits (Biosino
Company Limited ( Jinan, China). The peptide content
Bio-technology and Science Inc., Beijing, China) using an
was $ 80 %.
automatic biochemical analyser (Type AU2700; Olympus,
Tokyo, Japan). ApoAI, apoB and apoE were determined by
Animals, diets and experimental protocol
immunoturbidimetry using assay kits from Biosino Bio-
A total of sixty healthy male Sprague –Dawley rats were technology and Science Inc. These procedures were fully
obtained from the Laboratory Animal Center of the Third automated and have been described in detail elsewhere(14).
 Effects of soya oligosaccharides and oligopeptides 605

Evaluation of antioxidant activities. Superoxide dismutase Table 1. Effects of soya oligosaccharides (SOS) and soya oligopep-
(SOD) activity in the serum and liver was determined by the tides (SOP) on body weight and food intake of rats*
xanthine oxidase method using a commercially available (Mean values and standard deviations, n 12 per group)
kit (SOD Detection Kit; Nanjing Jiancheng Bioengineering
Initial Final Weight Food
Institute, Nanjing, China)(15). Malondialdehyde (MDA) in the weight (g) weight (g) gain (g) intake (g/d)
serum and liver was measured by the thiobarbituric acid
method(16) using a commercially available kit (MDA Detection Group Mean SD Mean SD Mean SD Mean SD

Kit, Nanjing Jiancheng Bioengineering Institute). The assay Control 240 16 320 21 78 16 15·4 4·3
was based on the ability of a chromogenic agent to react HFD 237 15 368 23 129 27 17·5 4·0
SOS 238 19 363 25 122 24 19·1 6·5
with MDA, yielding a stable chromophore with maximal SOP 239 16 373 27 130 20 17·9 5·0
absorbance at 532 nm. SOSP 238 19 374 25 131 20 18·7 4·5
Prostanoid release measurements. In order to measure the
HFD, high-fat diet; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
release of thromboxane A2 (TXA2) and prostacyclin (PGI2), * There were no significant difference between groups.
direct RIA was carried out to determine the concentrations
of thromboxane B2 and 6-ketoPGF1a, the stable degradation data with normal distribution and homogeneity of variance, sig-
products of TXA2 and PGI2, respectively(17). RIA kits were nificance of difference (P,0·05) between mean values was deter-
supplied by the General Hospital of PLA, Beijing, China. mined by ANOVA coupled with the least significant differences
Plasma nitric oxide assay. Plasma NO concentration was (LSD) test, whereas it was determined by the Dunnett-T3 test
determined by colorimetric technique and nitrate reductase for data with heterogeneity of variance.
British Journal of Nutrition

method using a Nitrate/Nitrite Colorimetric Assay kit (Nanjing

Jiancheng Bioengineering Institute). This assay was based on
the enzymatic conversion of nitrate to nitrite by nitrate redu- Results
ctase, and the concentration of NO was indirectly measured
Body weight and food intake
by determining both nitrate and nitrite levels in the plasma.
Determination of faecal bile acids. Total FBA was deter- Table 1 shows that neither the pre-treatment BW of rats nor
mined by spectrophotometry based on the colour reaction weight gains after the 8-week treatment were significantly
between phosphomolybdate and bile acid(18). Protein and pig- different among the five groups. The mean daily food intake
ment were precipitated from faeces by adding ethanol, and of rats in the HFD and experimental groups was higher than
total bile acids were extracted by chloroform and methanol that of the control group during the 8-week experiment; how-
(2:1, v/v). Phosphomolybdate reagent (phosphomolybdate ever, the difference was not statistically significant.
(2·5 g), glacial acetic acid (100 ml) and concentrated sulphuric
acid (10 ml)) was used to form colour reaction, and then it was
Lipid profile changes
quantified by a 721 spectrophotometer (wavelength: 690 nm)
(Shanghai Phenix Optical Scientific Instrument Company Lim- Table 2 shows the effects of SOS and SOP on serum TC, TAG,
ited, Shanghai, China). LDL-C and HDL-C levels. Serum TC, TAG and LDL-C levels in
the HFD group were significantly higher than those of the
control group, whereas HDL-C level was significantly lower
Statistical analysis
than that of the control group (P, 0·05). The addition of
All statistical calculations were carried out with Statistical Package SOS and SOP alone or together with HFD resulted in signifi-
of SPSS 13.0 (Release 13.01S China: Beijing Stats Data Mining cantly decreased serum TC, TAG and LDL-C levels, whereas
Company Limited, Beijing, China; permanent license). Data HDL-C level was significantly increased compared with the
were expressed as mean values and standard deviations. For HFD group (P,0·05). In particular, the combination of SOS

Table 2. Effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on lipid profile of rats
(Mean values and standard deviations, n 12 per group)

TC (mmol/l) TAG (mmol/l) LDL-C (mmol/l) HDL-C (mmol/l)

Group Mean SD Mean SD Mean SD Mean SD

Control 2·59 0·25 0·29 0·02 1·03 0·23 1·50 0·13

HFD 6·26* 0·52 2·76* 0·28 4·68* 0·35 1·04* 0·13
SOS 3·90*† 0·34 1·37*† 0·14 1·90*† 0·27 2·28*† 0·13
SOP 4·09*† 0·23 1·65*†‡ 0·08 1·55*†‡ 0·24 2·21*† 0·11
SOSP 3·50*†‡§ 0·19 1·31*†§ 0·07 1·07†‡§ 0·22 2·42*†‡§ 0·10

TC, total cholesterol; LDL-C, LDL-cholesterol; HDL-C, HDL-cholesterol; HFD, high-fat diet; SOSP, HFD enriched with
2 % SOS and 3 % SOP.
* Mean values were significantly different from those of the control group (P, 0·05).
† Mean values were significantly different from those of the HFD group (P,0·05).
‡ Mean values were significantly different from those of the SOS group (P,0·05).
§ Mean values were significantly different from those of the SOP group (P,0·05).
 606 S. Xie et al.

6·0 ApoE level of the three experimental groups was significantly

* lower than that of the HFD group (P, 0·05), and the values
5·0 were not statistically different from the control except for
the SOS group. Comparisons within the three experimental
AI (LDL-C/HDL-C)

4·0 groups revealed that the significant difference was only

obtained between the SOS and SOSP groups (P,0·05).
3·0 In terms of the apoB:apoAI ratio, it was significantly
increased in the HFD group compared with that of the control
2·0 group, whereas it was significantly decreased in the three
experimental groups compared with that in both HFD and
1·0 † † control groups (P,0·05). Furthermore, the apoB:apoAI ratio
†
of the three experimental groups was in an order as follows:
0·0 SOSP group , SOP group , SOS group (P,0·05).
Control HFD SOS SOP SOSP
Fig. 1. Changes of atherosclerosis index (AI). Values are means and stan-
dard deviations represented by vertical bars. * Mean value was significantly Effects of soya oligosaccharides and soya oligopeptides
different from that of the control group (P, 0·05). † Mean values were signifi-
cantly different from that of the high-fat diet (HFD) group (P, 0·05). LDL-C,
on vasoactive substances
LDL-cholesterol; HDL-C, HDL-cholesterol; SOP, soya oligopeptides; SOS,
Table 4 shows the effects of SOS and SOP on plasma vasoactive
soya oligosaccharides; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
substances. Plasma PGI2 and NO levels of the HFD group were
British Journal of Nutrition

and SOP was significantly more effective than SOS and SOP significantly lower than those of the control group, whereas
alone in altering TC, LDL-C and HDL-C levels (P, 0·05). TXA2 and the TXA2:PGI2 ratio of the HFD group were signifi-
Fig. 1 shows the change of AI value of each group. AI value cantly higher than those of the control group (P, 0·05).
of the HFD group was significantly higher than that of the con- Plasma PGI2 and NO levels of the three experimental groups
trol group, whereas the value of the three experimental were significantly higher than those of the HFD group, whereas
groups was significantly lower than that of the HFD group TXA2 and the TXA2:PGI2 ratio of the three experimental groups
(P,0·05). There was no statistically significant difference were significantly lower than those of the HFD group, but
among the control and experimental groups. higher than those of the control group (P,0·05). Compared
within the three experimental groups, the SOSP group was
more effective in reducing TXA2 and the TXA2:PGI2 ratio, as
Effects of soya oligosaccharides and soya oligopeptides well as increasing NO than the SOS or SOP group (P, 0·05).
on plasma apo levels
Table 3 shows the effects of SOS and SOP on plasma apo
Superoxide dismutase activity and malondialdehyde
levels in rats. Plasma apoAI level in the HFD group was signifi-
content in livers and serum
cantly lower, whereas apoB and apoE levels were significantly
higher than those of the control group (P, 0·05). ApoAI levels Table 5 shows that SOD activity in the serum, as well as MDA
of the three experimental groups were significantly increased contents in the liver and serum of the HFD group were signifi-
compared with the HFD and control groups (P, 0·05), and the cantly higher than those of the control group (P,0·05), whereas
most significant effect was observed in the SOSP group SOD activity in the liver of the HFD group was not statistically
(P,0·05). ApoB levels of the SOP and SOSP groups were sig- different from that of the control group. SOD activity in the
nificantly decreased compared with those of the other three liver of the three experimental groups was significantly lower
groups, and apoB level of the SOS group was significantly than that of the control group (P, 0·05). SOD activity in
decreased compared with that of the HFD group (P, 0·05). serum and the MDA content in the liver and serum of the

Table 3. Effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on plasma apo
levels of rats
(Mean values and standard deviations, n 12 per group)

ApoAI (g/l) ApoB (g/l) ApoE (mg/l) ApoB:apoAI

Group Mean SD Mean SD Mean SD Mean SD

Control 0·81 0·02 0·66 0·15 37·1 2·6 0·82 0·18

HFD 0·45* 0·03 0·90* 0·03 46·8* 3·7 1·99* 0·19
SOS 1·34*† 0·02 0·51† 0·04 33·1*† 3·0 0·38*† 0·04
SOP 1·42*†‡ 0·08 0·40*†‡ 0·02 35·9† 2·6 0·28*†‡ 0·01
SOSP 1·51*†‡§ 0·06 0·35*†‡ 0·03 36·9†‡ 2·0 0·23*†‡§ 0·02

HFD, high-fat diet; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
* Mean values were significantly different from those of the control group (P, 0·05).
† Mean values were significantly different from those of the HFD group (P, 0·05).
‡ Mean values were significantly different from those of the SOS group (P,0·05).
§ Mean values were significantly different from those of the SOP group (P,0·05).
 Effects of soya oligosaccharides and oligopeptides 607

Table 4. Effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on vasoactive substances of rats
(Mean values and standard deviations, n 12 per group)

TXA2 (ng/l) PGI2 (ng/l) NO (mmol/l) TXA2:PGI2

Group Mean SD Mean SD Mean SD Mean SD

Control 97 8 136 5 35·4 2·1 0·72 0·05

HFD 511* 27 86* 9 23·8* 2·0 6·01* 0·77
SOS 209*† 18 158*† 11 37·3† 2·2 1·33*† 0·12
SOP 237*†‡ 23 144†‡ 9 35·4† 2·0 1·65*†‡ 0·16
SOSP 186*†‡§ 10 146*†‡ 10 38·6*†§ 2·4 1·28*†§ 0·12

TXA2, thromboxane A2; PGI2, prostacyclin; NO, nitric oxide; HFD, high-fat diet; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
* Mean values were significantly different from those of the control group (P,0·05).
† Mean values were significantly different from those of the HFD group (P, 0·05).
‡ Mean values were significantly different from those of the SOS group (P, 0·05).
§ Mean values were significantly different from those of the SOP group (P, 0·05).

three experimental groups were significantly higher than those five groups, indicating that the consumption of diet by rats
of the control group, but lower than those of the HFD group was not altered by high fat, SOS and SOP, and thus the BW
(P,0·05), except for the liver MDA content of the SOSP gains were not significantly different among the five groups.
group, which was not significantly different from that of the The reduction of TC or LDL-C in plasma has been reported to
control group. Among the three experimental groups, the reduce the risk of CVD. Numerous studies in human subjects
British Journal of Nutrition

MDA content in the liver of the SOSP group was significantly and animals have shown the hypocholesterolaemic effect of
lower than that of the SOS group (P, 0·05), whereas no signifi- soya protein(10,19,20). Some studies reported that the effect of
cance was obtained from the other experimental groups. soya protein on lipid metabolism is attributed to its component
of peptides(21,22). In the present study, we observed that serum
TC and TAG of the SOP group were decreased by 34·7 and
Dry faecal weight and bile acid excretion 40·2 % compared with the HFD group, respectively. These
Table 6 shows the FBA levels of rats. Dry faecal weight of the results are consistent with findings of Duranti et al.(22), who
HFD group and the three experimental groups were higher showed that plasma TC and TAG of rats fed a hypercholestero-
than that of the control group. However, there were no signifi- laemic diet were reduced by 36 and 34 %, respectively, by treat-
cant differences among any groups (P.0·05). FBA of the three ment with 20 mg/kg BW per d of soya 7S globulin-a’ subunit for
experimental groups was significantly higher than that of the 28 d. By suppressing cholesterol micelle solubility, Zhong
HFD and control groups, and FBA of the HFD group was sig- et al.(23) showed that SOP interferes with the micellar solubil-
nificantly higher than that of the control group (P, 0·05). isation of cholesterol, resulting in decreased intestinal choles-
Compared with the three experimental groups, FBA content terol absorption and ensuing serum cholesterol reduction.
of the SOSP group was significantly higher than that of the Chen et al.(24) reported that SOS effectively reduces serum TC
other two experimental groups (P, 0·05). and TAG levels, thus improving the HFD-induced abnormal
blood lipid level in rats. Similarly, the present study showed
that SOS reduced serum TC and TAG concentrations of hyperli-
Discussion
pidaemic rats by 37·7 and 50·4 %, respectively. With a powerful
In the present study, we did not observe significant differ- prebiotic ability, SOS is fermented in the colon by bifidobacter-
ences of the mean daily food intake and BW gains among ium, yielding large amounts of SCFA, such as butyrate and
Table 5. Effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on superoxide dismu-
tase (SOD) activity and malondialdehyde (MDA) content in liver and serum of rats
(Mean values and standard deviations, n 12 per group)

SOD MDA

Livers Livers
(U/mg protein) Serum (U/ml) (nmol/g liver) Serum (nmol/l)

Group Mean SD Mean SD Mean SD Mean SD

Control 662 26 346 16 12·8 1·9 5·98 0·21

HFD 598 60 738* 69 29·6* 4·5 16·52* 0·99
SOS 581* 41 424*† 41 23·6*† 4·2 8·47*† 0·72
SOP 565* 100 428*† 53 19·9*† 8·6 7·99*† 0·52
SOSP 572* 35 423*† 51 15·2†‡ 4·2 7·84*† 0·48

HFD, high-fat diet; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
* Mean values were significantly different from those of the control group (P,0·05).
† Mean values were significantly different from those of the HFD group (P,0·05).
‡ Mean values were significantly different from those of the SOS group (P,0·05).
 608 S. Xie et al.

Table 6. Effects of soya oligosaccharides (SOS) and soya oligopep- especially their combination, were auxiliary in decreasing the
tides (SOP) on faecal dry weight and bile acids of rats risk of atherosclerosis and CVD.
(Mean values and standard deviations, n 12 per group) High apoB, the structural protein of LDL, and a high
apoB:apoAI ratio are strongly related to the increased athero-
Dry weight Bile acids
(g/3 d) (mg/g dry weight) sclerotic cardiovascular risk. In contrast, high apoAI, mainly
representing HDL and being crucial in transferring cholesterol
Group Mean SD Mean SD
from tissues to the liver, is inversely related to atherogenic
Control 13·2 3·1 48 8 risk(34). In the present study, we observed a significantly
HFD 14·6 1·9 126* 20 higher apoB and apoB:apoAI ratio, exhibiting an atherogenic
SOS 15·5 2·4 167*† 7
SOP 15·1 4·0 151*† 13
lipid profile as well as a significantly lower apoAI in HFD-fed
SOSP 17·2 4·1 196*†‡§ 16 rats. The present data also showed a significant reduction of
apoB by 43·3 % and an increase of apoAI by 197·8 % in SOS-
HFD, high-fat diet; SOSP, HFD enriched with 2 % SOS and 3 % SOP.
* Mean values were significantly different from those of the control group (P,0·05).
fed rats. In a clinical study, Teixeira et al.(20) observed that
† Mean values were significantly different from those of the HFD group (P,0·05). soya protein effectively reduces plasma apoB, whereas the
‡ Mean values were significantly different from those of the SOS group (P,0·05).
§ Mean values were significantly different from those of the SOP group (P,0·05).
change in apoAI is not significant. However, in the present
study, SOP not only reduced apoB but also increased apoAI
propionate(25). It has been hypothesised that SCFA, in particular effectively. Moreover, the combination of SOP and SOS
propionate and butyrate, are able to influence lipid metab- showed a more marked effect on reducing the apoB:apoAI
olism(26). Butyrate can inhibit hepatic cholesterol synthesis, ratio and increasing apoAI than SOP and SOS alone. These
British Journal of Nutrition

while propionate may inhibit the synthesis of fatty acids in the data indicated that the combination of SOP and SOS could
liver, thereby reducing the rates of TAG secretion(27). Therefore, be more effective in reducing serum lipid risk factors for
the present data suggested that the improved lipid metabolism CVD than SOP or SOS alone.
observed in the SOS group was partly caused by an alteration Endothelial dysfunction plays an important role in the early
development of atherosclerosis(35). PGI2 and NO are anti-
in the absorption and/or synthesis of cholesterol through
atherogenic because of their vasodilating effects, whereas
SCFA. In the present study, we observed that the combined
TXA2 is a potent vasoconstrictor(36 – 38). In the present study,
treatment of SOS and SOP reduced TC and TAG levels by
we observed that HFD reduced the release of PGI2 and NO,
10·3, 14·4 and 4·4 %, 20·6 % compared with SOS and SOP
and increased the TXA2 level, suggesting that endothelium-
alone, respectively, suggesting that the combination of SOS dependent vasorelaxation was attenuated by hyperlipidae-
and SOP was more effective in improving dyslipidaemia, thus mia(39), and the effect of hypercholesterolaemia on endothelial
reducing the risk of atherosclerotic CVD. cells leads to the inhibition of NO synthesis(35). In vitro study
There is increasing evidence that both reducing LDL-C and has shown that SOP increases the release of PGI2 and NO, but
raising HDL-C can result in significant cardiovascular ben- it does not affect TXA2 (40). The present study showed that SOP
efit(28). In the present study, LDL-C was reduced by 66·9 % in not only increased the release of PGI2 and NO by 67·9 and
the SOP group and by 59·4 % in the SOS group, whereas 48·9 %, respectively, but also decreased TXA2 by 53·6 % com-
HDL-C was increased by 112·5 and 119·2 %, respectively. pared with the HFD group. SOS exerted similar effects.
These results suggested that these effects of SOS and SOP on Furthermore, the combination of SOS and SOP was more
LDL-C and HDL-C were beneficial for atherosclerotic CVD. effective in reducing TXA2 and the TXA2:PGI2 ratio, as well
Some studies confirmed the reduction in plasma TC and LDL- as increasing NO than SOS or SOP alone, thus improving
C without significant effect on HDL-C by soya protein(19,29). endothelial dysfunction and cardiovascular health.
Zhao et al.(30) observed that SOP reduces serum TC and TAG It has been shown that oxidative stress contributes to endo-
levels of hyperlipidaemic rats, whereas HDL-C is not signifi- thelial dysfunction and atherosclerosis(2). However, dietary
cantly altered. However, we observed a significant increase of antioxidants may protect against oxidative events in the
plasma HDL-C in the SOP group. The precise reason for this body, and the antioxidant activity reduces CVD by preventing
LDL oxidation(35,41). In the present study, oxidative stress
inconsistency with other reports remains unclear. It may
occurred in HFD-fed rats with elevated liver and serum
result from the SOP used in the present study, which was differ-
levels of MDA, the ultimate product of lipid peroxidation.
ent from other studies, especially the molecular weight of SOP.
The antioxidant defence system, such as SOD, is important
It has been proposed that the regulation of cholesterol homo-
to protect the body from oxidative damage(42). Many exper-
eostasis by SOP depends on the activation of LDL receptors
imental results showed that HFD or hyperlipidaemia can
and LDL degradation in the liver(31). Lovati et al.(32) demon- reduce SOD activity in rats(43). Surprisingly, in the present
strated that peptides derived from soya 7S globulin-a’ subunit study, the serum SOD activity of the HFD group was not
are able to up-regulate LDL receptors’ activity, thus resulting reduced, and it was higher than that of the control and exper-
in receptor-mediated LDL catabolism(33). However, 7S lacking imental groups. The present findings are consistent with those
the a’-subunit has no effect on the up-regulation of LDL recep- of Arafa et al.(44), who showed that a HFD does not decrease
tors, indicating that soya peptides with hypocholesterolaemic the liver SOD activity, which is higher than that of normal diet-
activity are involved in the regulation of LDL receptors. The fed rats and curcumin-treated rats. We supposed that the result
observed decrease in AI values suggested that SOS and SOP, was due to the high level of MDA, which resulted in the
 Effects of soya oligosaccharides and oligopeptides 609

increase of SOD activity for maintaining the balance between FBA excretion by the combination of SOS and SOP could be
oxidative stress and antioxidant defences. ascribed to an additive or synergistic effect.
Gibbs et al.(45) reported that the antioxidant activity of soya In summary, the present study shows that ingestion of 2 %
protein is associated with the fractions 11S or glycinin as the SOS or 3 % SOP influence lipid metabolism, release of vaso-
precursor of antioxidant peptides. In another study, it has active substances as well as antioxidant activity and increase
been shown that the ingestion of soya peptide in rats reduces FBA excretion. In particular, the combination of 2 % SOS
paraquat-induced oxidative stress by preventing the elevation and 3 % SOP is more effective than SOS or SOP alone,
of the concentration of serum thiobarbituric acid-reactive especially in improving the lipid profile and increasing FBA
substances, thus effectively preventing LDL oxidation(46). The excretion. These results indicate that SOS and SOP have
present data show that SOP decreases MDA by 32·8 and potential value in CVD prevention. Further studies should
51·6 % in the liver and serum, respectively, thus reducing focus on clarifying the mechanisms of action of the lipid
oxidative stress. Chen et al.(47) found that peptides with a Pro- effects of SOS and SOP.
His-His sequence demonstrate the greatest antioxidant activity
among all tested peptides, and their activity is decreased by Acknowledgements
removing a His residue from the C-terminus. Chen et al.(24)
The authors thank the Department of Nutrition and Food
reported that the activities of antioxidant enzymes in the liver
Hygiene, Third Military Medical University, for laboratory
and serum, such as catalase and SOD, are significantly elevated
and technical support of the present study. They are also
when SOS is orally administered to rats for 45 d. The present
grateful to Dr Fang Chen and Junhua Peng for their valuable
data show that SOS could reduce oxidative stress by increasing
discussions on the methods of bile acid measurement. This
British Journal of Nutrition

the serum SOD activity and reducing the MDA content in

work was supported by the Sci & Tech Research Project Foun-
SOS-treated rats, suggesting that SOS protected blood vessels
dation of Scientific Committee of Chongqing (200300168).
and endothelial cells from oxidative damage by inhibiting LDL
S. X., J. Z. and X. M. designed the research; S. X. conducted
oxidation, thus protecting against atherosclerosis. the research; Y. Z., K. S. and Y. S. analysed the data; and
Bile acids are critical in maintaining cholesterol homoeosta- S. X. and J. Z. wrote the manuscript.
sis. Binding of bile acids and increasing their faecal excretion
have been hypothesised as an effective way to reduce choles-
terol by dietary factors(48). Iwami et al.(49) reported that SOP
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