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Prev. Nutr. Food Sci. 2013;18(3):169-174 
http://dx.doi.Org/1 0.3746/pnf.201 3. 1 8.3. 1 69 
pISSN 2287-1098 • elSSN 2287-8602 

In vivo Investigation of Anti-diabetic Properties of Ripe Onion 
Juice in Normal and Streptozotocin-induced Diabetic Rats 

Chul-Won Lee 1 , Hyung-Seok Lee 2 , Yong-Jun Cha 3 , Woo-Hong Joo 4 , Dae-Ook Kang 5 , and Ja-Young Moon 5 

institute of Marine BioTechnology, Pusan National University, Busan 609-735, Korea 
2 KT&G Central Research Institute, Daejeon 305-805, Korea 

department of Food and Nutrition, department of Biology, ^Department of Biochemistry and Health Sciences, 
Changwon National University, Gyeongnam 641-773, Korea 



ABSTRACT: The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice 
(Commercial product name is "Black Onion Extract") were investigated in normal and streptozotocin-induced diabetic 
rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by 
oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests 
were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper- 
glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single 
dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 
5 or 15 mlVkg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a rela- 
tively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glu- 
cose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats 
were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypo- 
glycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mLAg b.w.) for a short 
period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced dia- 
betic rats. In conclusion, these results suggest that the commercial product "Black Onion Extract" may possess anti- 
hyperglycemic potential in diabetes. 

Keywords: anti -diabetic, Endoplasmic Reticulum stress, hypoglycemic effect, onion, streptozotocin 



INTRODUCTION 

Diabetes mellitus is a metabolic disorder affecting the 
metabolism of carbohydrate, fat and protein. The disease 
is classified as type 1 diabetes due to islet beta-cell de- 
struction, type 2 diabetes with varying degree of insulin 
resistance and/or insulin secretion deficiency, gesta- 
tional diabetes, and other specific types of diabetes (1). 
Type 2 diabetes mellitus is the most common form of 
diabetes, accounting for 90~95% of all diabetic patients. 
Type 2 diabetes mellitus is a heterogeneous disorder 
characterized by a progressive decline in insulin action 
(insulin resistance), followed by the inability of [3-cells 
to compensate for insulin resistance (p-cell dysfunction) 
(2). Controlling hyperglycemia, tight control of blood 
glucose levels and prevention of diabetic complications 
are the major goals in Type 2 diabetes treatment (1). 
Recently there has been a growing interest in alter- 



native therapies, including the use of plant foods, to 
treat diabetic patients (3). Onion {Allium cepa L.) is a 
bulbous herb belonging to the vegetable family Alliceae, 
and is a widely used food ingredient as well as a com- 
mon spice all over the world. Onion is one of the richest 
sources of flavonoids and organosulfur compounds that 
possess strong antioxidant activities (4-6). Thus, onion 
intake is reported to have several beneficial effects on 
health, such as preventing tumors and cancers (7,8), car- 
diovascular diseases (9), hypertension (10), hypoglyce- 
mic and hypocholesterolemic effects (11,12) as well as 
improving diabetic status (12-14). 

A number of studies have focused on the ability of on- 
ion to ameliorate diabetes, with many of them reporting 
both hypoglycemic and hypolipidemic effects in animal 
models of chemically induced non-insulin-dependent 
diabetes (12,15,16). However, the effects of ripe onion 
juice on hypoglycemic activity and on anti-diabetic activ- 



Received July 4, 2013; Accepted August 5, 2013 

Correspondence to Ja-Young Moon, Tel: +82-55-213-3552, E-mail: jymoon@changwon.ac.kr 
Copyright © 2013 by The Korean Society of Food Science and Nutrition. All rights Reserved. 

© This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.Org/licenses/by-nc/3.0) which permits 
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 



170 



Lee et al. 



ity have not been evaluated. Hence, in the present study, 
we investigated the effect of ripe onion juice, commer- 
cially called "Black Onion Extract", on blood glucose 
levels in glucose-fed hyperglycemic, streptozotocin (STZ)- 
induced diabetic and normal rats compared to tolbuta- 
mide as a reference standard. 

MATERIALS AND METHODS 

Preparation of "Black Onion Exract" 

In this study, we used a commercial product "Black 
Onion Extract", a drinkable ripe onion juice, manufac- 
tured by New Green Food Co., Ltd. (Changnyeung, 
Korea). According to the company, the "Black Onion 
Extract" was manufactured through the processing of 
ripening the onion for 16 days. Detailed ripening con- 
dition for 16 days was as follows: for first day at 0°C, for 
second day through fourth day at 78°C, for fifth day 
through seventh day at 45°C, for eighth day through 
tenth day at 60°C, for eleventh day through thirteenth 
day at 75°C, and for last three days at 50°C. During the 
ripening period, onion coats with the concentrated func- 
tional components were produced. By applying Steam 
Emission Extract method, ingredients of onion were con- 
centrated to the "Black Onion Extract" and the residual 
unpleasant smell of onions was effectively eliminated. 

Acute toxicity 

The acute toxicity test was performed by administration 
of ripe onion juice using oral gastric gavages at doses of 
5, 10, 15, 20 and 25 mLAg b.w. to groups of 6 male 
Sprague-Dawley rats, and maintained for 14 days. Gen- 
eral behavior of rats was recorded continuously for 12 h 
and daily for a further 2 weeks for any eventual mortality. 

Determination of the blood glucose levels 

Blood glucose concentrations were measured using au- 
tomatic analysis (Accu-Chek Active Glucose, Roche 
Diagnostics, Mannheim, Germany) . 

Effect in normoglycemic animals 

Fasting blood glucose level of each animal was de- 
termined at the beginning of the experiment, after over- 
night fasting with free access to water. The ripe onion 
juice (5 and 15 mLAg b.w.) was single dosed using oral 
gastric gavages to test groups of animals. Tolbutamide 
(250 mgAg b.w.) was single dosed using oral gastric 
gavages to the positive control group. Blood samples 
were collected from tail vein every 0.5 h for 4 h after the 
oral administration of test samples. 

Oral glucose tolerance test (OGTT) 

Fasting blood sugar level of each rat was determined at 



zero-time, after overnight fasting with free access to 
water. Glucose (5 gAg b.w.) was orally administered 30 
min after oral administration of the test samples or ve- 
hicle (for control). Blood glucose concentrations were 
measured just before and 0.5, 1, 1.5, 2, 3, and 4 h after 
the oral administration of the test samples. 

Effects on streptozotocin-induced diabetic rats 

Induction of diabetes: Diabetes was induced in male 
Sprague-Dawley rats (160~200 g) by the intraperitoneal 
injection of streptozotocin (STZ) at a single dose of 60 
mgAg b.w. dissolved in 0.1 M citrate buffer, pH 4.5. 
Two days after STZ injection, blood glucose levels were 
measured by using a glucometer (Johnson & Johnson, 
New Brunswick, NJ, USA) and the animals with blood 
glucose levels above 300 mg/dL were considered 
diabetic. Diabetic rats (blood glucose level ^300 mg/dL) 
were subdivided into three groups (n=6 per group): 
group I received only natural food, group II orally re- 
ceived the Black Onion Extract (15 mLAg b.w, single), 
and group III orally received tolbutamide (250 mg/kg b.w.). 
Determination of hypoglycemic activity on acute administration: 
Test samples were given orally using oral gastric gavages 
to the overnight fasted animals. The blood glucose con- 
centrations of the animals were measured at the begin- 
ning of the study and the measurements were repeated at 
0.5, 1, 2, 4 and 6 h after the initiation of the experiment. 
Determination of hypoglycemic activity on subacute admini- 
stration: The ripe onion juice (15 mLAg b.w.) was ad- 
ministered once a day for 7 consecutive days using oral 
gastric gavages. Blood glucose level of each animal was 
determined at 1st, 3rd, 5th and 8th days after the ad- 
ministration of the ripe onion juice. Body weight of ani- 
mals was also monitored on these days. 

Statistical analysis 

Results are expressed as means ±SEM for groups of six 
animals each, and differences between groups were test- 
ed for significance using two-way analysis of variance 
(ANOVA) followed by a. post-hoc Duncan's multiple range 
test. The statistical analyses were performed on a Stati- 
stical Package for the Social Sciences (SPSS) version 18.0 
(SPSS Inc., Chicago, IL, USA). 

RESULTS 

Acute and subacute toxicity of ripe onion juice 

Toxicity of ripe onion juice in Sprague-Dawley rats was 
tested using oral gastric gavages at doses of 5, 10, 15, 20 
and 25 mLAg b.w. for 14 days. No rats at all dose ranges 
were dead until the end of the study, indicating that the 
tolerated dose of ripe onion juice was above 25 mLAg 
body weight. Ripe onion juice at all doses used in this 



Anti-diabetic Properties of Ripe Onion Juice 



171 



study did not show mortality or any remarkable symp- 
toms of toxicity and/or any significant changes in gen- 
eral behavior in rats. The body weight gains of rats were 
not affected by the treatment. These results suggest that 
ripe onion juice has no acute and subacute toxic effects 
in Sprague-Dawley rats. 

Acute hypoglycemic effect of ripe onion juice in normal rats 

As a preliminary activity assessment, the ripe onion 
juice was administered to normal rats at two dose levels 
(5 and 15 mL/kg b.w.) to determine the acute effects on 
blood glucose concentrations. Changes in the blood glu- 
cose level of each group of animals were followed during 
a 4 h period. As shown in Table 1, the fasting blood glu- 
cose levels in the tested rats ranged between 59 and 66 
mg/dL and no remarkable acute hypoglycemic effect of 
ripe onion juice was observed in normal rats. Admini- 
stration of the ripe onion juice at both concentrations (5 
and 15 mVkg b.w.) in the fasted rats exhibited overall 
increase in their glucose levels through the duration of 
the experiment. At 0.5 h after the ripe onion juice (5 



and 15 mLAg b.w.) doses, glucose levels were tran- 
siently increased compared to that in the untreated con- 
trol group, suggesting that no remarkable effect on hypo- 
glycemic activity by the ripe onion juice. Tolbutamide 
(250 mgAg b.w., single oral dose) in control rats did 
not exhibit any significant alteration (hypoglycemic ef- 
fect) in these glucose levels either through the duration 
of the experiment. 

Oral glucose tolerance test in normal rats dosed with ripe 
onion juice 

Results of the glucose tolerance test performed on nor- 
mal rats dosed with ripe onion juice (5 and 15 miykg 
b.w.) are shown in Table 2. At thirty minutes after feed- 
ing with glucose (5 g/kg b.w., oral), the blood glucose 
level increased to 185 (247%) and 157.8 (240%) mg/dL 
in normal control group and in the tolbutamide dosed 
group, respectively, representing as a hyperglycemic peak. 
Administration of ripe onion juice with 5 and 15 mLAg 
b.w. at thirty minutes after feeding with glucose (5 gAg 
b.w., oral) also increased the blood glucose level to 



Table 1. Effects of a single oral dose of ripe onion juice and tolbutamide on blood glucose level in overnight fasted normal rats 

Blood glucose (mg/dL) 



Time (h) 


Control 


Onion juice 
(5 mL/kg b.w.) 


Onion juice 
(15 mL/kg b.w.) 


Tolbutamide 
(250 mg/kg b.w.) 


P-value 


Fasting (0) 


63±4 b 


59+1 a 


66±6 a 


61+3 


NS 


0.5 


62±3 Ab 


101+5 Bd 


125+12 Ce 


61+6 A 


0.000*** 


1 


73±5 Ac 


85+4 Bb 


101+2 cd 


66±6 A 


0.000*** 


1.5 


65±5 Ab 


83±4 Bb 


99±7 Cc 


68±4 A 


0.000*** 


2 


66±6 Ab 


88±7 Bb 


97+5 Cc 


66±2 A 


0.000*** 


2.5 


80±8 Bd 


84±3 Bb 


93±4 cb 


63±4 A 


0 000*** 


3 


68±5 Ab 


87+5 Bb 


84+6 Bb 


60+4 A 


0.000*** 


3.5 


59±3 Aa 


90+3 Bc 


96+3 Bc 


67±2 A 


0 000*** 


4 


64±5 Ab 


80±8 Bb 


90±2 Bb 


62±4 A 


0 000*** 


P-value 


0.000*** 


0.000*** 


0.000*** 


NS 





Values are given in mean±SEM for groups of six animals each. Capital letters signify the results of post-analysis for groups in 
post-hoc Duncan's multiple range test and lower-case alphabets signify the results of post-analysis for time, respectively. 
***/°<0.001. 



Table 2. Effects of a single oral dose of ripe onion juice and tolbutamide on blood glucose level in oral glucose (5 g/kg) tolerance 
test in Sprague-Dawley rats 

Glucose tolerance test (mg/dL) 



Time (h) 


Control 


Onion juice 
(5 mL/kg b.w.) 


Onion juice 
(15 mL/kg b.w.) 


Tolbutamide 
(250 mg/kg b.w.) 


P-value 


0 


61.3±2.7 a 


61.2±2.7 a 


62.5±2.7 a 


59.8±3.8 a 


NS 


0.5 


60.5±2.5 Aa 


108.6±4.5 Bc 


137+1 1.2 Cc 


60.6±6.5 Aa 


0.000*** 


1 1) 


75.0±3.0 Ba 


85.0+3.6 cb 


101.4+2.2 Db 


65.8±5.8 Aa 


0.000*** 


1.5 


185±11.5 d 


181.4+10.3 6 


193+16.8" 


157.8±39.0 b 


NS 


2 


158±14.6 C 


157.8+14.6 (13.0) d 


174.4+12.1 (9.6) d 


141.8+40.6 (10.2) b 


NS 


3 


148±6.3 Ac 


149.2+9.0 (5.5) Bd 


170.2±19.0 (2.4) Bd 


115.2±37.8 (18.8) Ab 


0.032* 


4 


122+17.6" 


104.8±9.3 (34.2) c 


1 1 5.8+12.6 (32.0) c 


110+27.2 (4.5) b 


NS 


P-value 


0.000*** 


0 000*** 


0 000*** 


0 000*** 





Glucose (5 g/kg b.w.) loaded. 

Values are given in mean±SEM for groups of six animals each. Values in parenthesis indicate the percentage lowering of blood 
glucose level in comparison to the previous time-point reading. Capital letters signify the results of post-analysis for groups in 
post-hoc Duncan's multiple range test and lower-case alphabets signify the results of post-analysis for time, respectively. */><0.05, 
***/°<0.001. 



172 



Lee et al. 



181.4 (213%) and 193 (190%) mg/dL, respectively. 
Nevertheless, after these substantial increases in glucose 
levels, the ripe onion juice administration significantly 
reduced the blood glucose levels to a level below that 
produced in the control group after three hours. Single 
oral dosage of tolbutamide (250 mg/kg b.w.) caused a 
significant reduction (27%) in glucose levels at 2 h after 
its administration, while for the same period of time af- 
ter glucose loading administration, the groups of ripe 
onion juice (5 and 15 mL/kg) showed a relatively slight 
reduction, i.e., 18% and 12 % decrease in glucose levels, 
respectively. At 3 h after glucose load, blood glucose lev- 
els in the ripe onion juice-administered groups ap- 
proached the level of tolbutamide-dosed group; this 
showed that the decrease (42.2%) in blood glucose lev- 
els at 3 h after glucose load was most efficient in the 5 
mL/kg ripe onion juice-administered groups, which was 
lower than the decrease (30.3%) level in the tolbuta- 
mide-dosed group. Particularly, compared to the ripe on- 
ion juice treated groups, the control rat group showed 
no remarkable decrease in glucose level even at 3 h after 
glucose load. 

Hypoglycemic effects of ripe onion juice on streptozoto- 
cin-induced diabetic rats 

As a preliminary activity assessment, ripe onion juice 
(15 mLAg b.w.) was administered to STZ-induced dia- 



betic rats to determine the acute effect on blood glucose 
concentrations under the diabetic condition. Changes in 
the blood glucose level in each group of rats were fol- 
lowed during a 6 h period. Administration of STZ (60 
mg/kg/i.p.) led to over a six-fold elevation in blood glu- 
cose levels compared to normal rats, which were main- 
tained over a period of 3 weeks (Table 3) . The oral ad- 
ministration of tolbutamide (250 mgAg b.w.) showed a 
significant reduction in glucose level throughout the ex- 
perimental period, especially at 0.5, 1 and 2 h after its 
administration. The administration of tolbutamide pro- 
duced a significant reduction in glucose level by 39 
mg/dL after 6 h, while for the same period of time, only 
a slight decrease in blood glucose level compared to con- 
trol was observed after the administration of ripe onion 
juice; however, the decrease was much comparable to 
that of the tolbutamide administrated group. The ad- 
ministration of ripe onion juice (15 mLAg b.w.) also 
produced a reduction in glucose level by 18 mg/dL after 
6 h, which is lower than the level decreased by tolbuta- 
mide administration. 

To determine possible subacute hypoglycemic effects 
of ripe onion juice and tolbutamide, first, a single intra- 
peritoneal administration of STZ into diabetic rats (60 
mgAg) led to over a five-fold elevation of blood glucose 
levels, which were maintained over a period of eight 
days (Table 4) . Orally administered tolbutamide showed 



Table 3. Effects of ripe onion juice and tolbutamide on blood glucose level in STZ-induced diabetic rats 

Mean blood glucose concentration±SEM (mg/dL) 

Time ' n ' Control Onion juice Tolbutamide p _ . 

(STZ-injected) (15 mL/kg b.w.) (250 mg/kg b.w.) rvalue 



0 323±7 b 326±5 b 323+8 b NS 

0.5 373±9 Bb 358+1 1 Bb 325±21 Ab 0.004** 

1 340+17 b 332+1 1 b 308+22 a NS 

2 333±13 Bb 329+13 Bb 301 + 17 Aa 0.045* 
4 311+14 a 309+7 a 310+10 a NS 

6 31 1 +8 Ba 308±10 Ba 284+10 Aa 0 001** 

P-value 0.000*** 0.000*** 0.025* 



Diabetes induction in male Sprague-Dawley rats was performed by the intraperitoneal injection of streptozotocin (STZ) at a single 
dose of 60 mg/kg body weight. 

Tolbutamide (250 mg/kg b.w.) or Onion Juice (15 mL/kg b.w.) was orally dosed in STZ-induced diabetic rats, respectively. Capital 
letters signify the results of post-analysis for groups in post-hoc Duncan's multiple range testand lower-case alphabets signify 
the results of post-analysis for time, respectively. */°<0.05, **P<0.01, ***P<0.001. 



Table 4. Subacute hypoglycemic effects of ripe onion juice and tolbutamide on STZ-induced-diabetic rats 



Treatment 

Control (Untreated) 
STZ treated 

Tolbutamide (250 mg/kg) 
Onion Juice (15 mL/kg) 



Mean blood glucose concentration±SEM (mg/dL) 



1st day 

61.3+1.5 
357±17 
363±8 
366±5 



3rd day 

61.2+1.2 
405±19 (-13) 
325±21 (11) 
378+1 1 (-3) 



5th day 

62.5+1.1 
368+17 (-3) 
308±22 (16) 
332+16 (9) 



8th day 



61.8:1 



.3 

338+13 (6) 
276+17 (24) 
315+8 (14) 



Values are given in mean±SEM for groups of six animals each. Values in parenthesis indicate the percentage lowering of blood 
sugar level in comparison to the reading at 1st day. 

Tolbutamide (250 mg/kg/day, single) or Onion Juice (15 mL/kg/day for 7 consecutive days) was orally dosed in STZ-induced diabetic 
rats, respectively. 



Anti-diabetic Properties of Ripe Onion Juice 



173 



a tendency of reduction (24%) in plasma glucose levels 
after eight days. Although showing weak hypoglycemic 
effect compared to that of tolbutamide, a single dose of 
ripe onion juice (15 mLAg) also reduced blood glucose 
in STZ-induced diabetic rats after its oral administration 
daily for eight days. 



DISCUSSION 

The objective of this study was to investigate whether 
the commercial product "Black Onion Extract", a drink- 
able ripe onion juice, could produce hypoglycemic activ- 
ity in normal rats and antihyperglycemic effect in strep- 
tozotocin-induced diabetic rats. The results from this 
study first indicate a potential use of onion (Allium cepa) 
as a beneficial anti-hyperglycemic food supplement in 
diabetes. Considerable numbers of studies have been re- 
ported about the antidiabetic effects of various forms of 
onions, including aqueous onion extracts (15,16), diet- 
ary onions (12,17) and isolated or synthesized active 
compounds in onions (13,14,18). All of these studies re- 
ported significant antihyperglycemic effects of onions 
and its compounds in alloxan- or STZ-induced diabetic 
rats. In the present study, we found that, although low/ 
weak hypoglycemic activity exhibited in normal rats, the 
commercial products of onions, drinkable ripe onion 
juice, possess antidiabetic potential in STZ-induced 
Sprague-Dawley rats. STZ is widely used for induction 
of experimental diabetes mellitus because of its toxic ef- 
fect to pancreatic p-cells, which are responsible for the 
secretion of insulin (19). Thus STZ-induced diabetes is 
characterized by uniform hyperglycemia. A clinically 
used tolbutamide (a sulphonylurea drug) is known to 
lower the blood glucose level by stimulating p-cells to 
release insulin (20). Since STZ induces diabetes by de- 
stroying p-cells and by impairing renal function (21), in 
the present study, tolbutamide exhibited mild hypo- 
glycemic activity in the STZ diabetic rats. 

In many clinical studies the hypoglycemic activity of 
Allium cepa has been demonstrated by showing that the 
addition of raw onion to the diet for non-insulin-depen- 
dent diabetic subjects decreased the dose of antidiabetic 
medication required to control the disease (22). More- 
over, the oral administration of Allium cepa crude hydro- 
alcoholic extract in alloxan-induced diabetic rats pro- 
duced a significant hypoglycemic activity and favorable 
good health effects, which may be most probably attrib- 
uted to improvement and/or regeneration of pancreatic 
P-cells (23) . Some articles report that Allium cepa acts as 
a hypoglycemic agent by directly acting on tissues such 
as the liver and muscles, and altering the activities of the 
regulatory enzymes of glycolysis, gluconeogensesis, and 
other pathways, such as attenuation of ER stress, rather 



than increasing insulin levels and creating extra pancre- 
atic effects (22,24,25). Recently, ER stress has been sug- 
gested to play a central role in the development of in- 
sulin resistance and diabetes by impairing insulin signal- 
ing (26-28); hence, effects of onion extracts or its com- 
ponents could possess the properties as potent anti- 
diabetic agents by alleviate ER stress and should be 
explored. 

Our results showed low hypoglycemic activity of ripe 
onion juice at two dose levels (5 and 15 mLAg b.w.) in 
the normal male Sprague-Dawley rats. A possible ex- 
planation is due to the short period of the experiment. 
Thus, further long term studies for the hypoglycemic ac- 
tivity of ripe onion juice are required. Another possible 
explanation for this result is that some ingredients, in 
particular, volatile sulfur compounds including thiosul- 
fonates and polysulfides for hypoglycemic activity might 
be loss during the product processing of ripe onion juice 
or by passing over its best distribution period. In fact, 
most of the sulfur compounds present in onions are in 
the form of cysteine derivatives, which are degraded dur- 
ing extraction by the enzyme allinase into a variety of 
volatile compounds including thiosulfonates and poly- 
sulfides (15). Kumari and Augusti (14) reported that 
S-methylcysteine sulfoxide isolated from onion has anti- 
hyperglycemic effect. Our observed increase in fasting 
blood glucose levels in the ripe onion juice-administered 
groups during the first 30 min after its oral dose is 
thought to be attributed to the glucogenic effects of 
Allium cepa, which might be from the cysteine present in 
onion (18). These glucogenic effects can counteract the 
common side effect (hypoglycemia) of antidiabetic agents 
currently used if Allium cepa is taken concurrently as a 
food supplement. 

Excessive consumption of high doses of onion can lead 
to adverse effects on health, such as anemia, weight loss, 
and toxicity to the heart, liver, and kidneys. One study 
showed that high doses (500 mgAg) given orally caused 
lung and tissue damage in rats (29) . Oral dosage (5 and 
15 mLAg b.w.) of the ripe onion juice used in this study 
corresponds to 2 and 6 mgAg b.w. by calculation, re- 
spectively, which are much lower contents from the con- 
centration showing the toxic effect. 

Our results show that the dose of ripe onion juice has 
antihyperglycemic activity is in agreement with reports 
previously published. Therefore, although detailed mech- 
anisms of action have remained for further investigation, 
we proposed that taking ripe onion juice may prevent 
hyperglycemia in diabetic rats. In conclusion, the pres- 
ent study suggests that ripe onion juice may be able to 
normalize the blood glucose levels when doses are con- 
tinuous for long periods. Although this paper is the only 
one reporting a drinkable commercial onion product 
containing antidiabetic potential, these findings provide 



174 



Lee et al. 



a basis for the use of this drinkable onion product for 
the prevention of diabetic patients. Thus, we suggest 
that usage of this product could be beneficial in pre- 
vention of type 2 diabetes mellitus. Of course, further 
studies for its long term effect for the prevention of dia- 
betes are required. 



ACKNOWLEDGMENTS 

This work was supported by the National Research 
Foundation of Korea Grant funded by the Korean 
Government MEST, Basic Research Promotion Fund 
(NRF-2009-013-C00041). This research was also finan- 
cially supported by Changwon National University in 
2011. We thank Mr. Jong-Soo Kyung, KT&G Central 
Research Institute for his technical support. We also 
thank Dr. Kwang-Hyun Cho, Changwon National 
University for his support of Statistical Analysis. 



AUTHOR DISCLOSURE STATEMENT 

The authors declare no conflict of interest. 



REFERENCES 

1. The Expert Committee on the Diagnosis and Classification 
of Diabetes Mellitus. 1997. Report of the expert committee 
on the diagnosis and classification of diabetes mellitus. 
Diabetes Care 20: 1183-1197. 

2. DeFronzo RA. 1997. Pathogenesis of type 2 diabetes: 
metabolic and molecular implications for identifying 
diabetes genes. Diabetes Rev 5: 177-269. 

3. Srinivasan K. 2005. Plant foods in the management of 
diabetes mellitus: spices as beneficial antidiabetic food 
adjuncts. Int J Food Sci Nutr 56: 399-414. 

4. Virtanen AL, Matikkala EJ. 1976. The isolation of S-methyl- 
L-cysteine sulphoxide and S-n-propyl-L-cysteine sulphoxide 
from onion {Allium cepa) and the antibiotic activity of 
crushed onion. Acta Chem Scand 13: 1898-1900. 

5. Block E. 1985. The chemistry of garlic and onions. Sci Am 
252: 94-99. 

6. Patil BS, Pike LM. 1995. Distribution of quercetin contents 
in different rings various coloured onion (Allium cepa L.) 
cultivars. ] Hortic Sci 70: 643-650. 

7. Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, 
Talamini R, Giacosa A, La Vecchia C. 2006. Onion and garlic 
use and human cancer. Am J Clin Nutr 84: 1027-1032. 

8. Belman S. 1983. Onion and garlic oils inhibit tumor pro- 
motion. Carcinogenesis 4: 1063-1065. 

9. Mennen LI, Sapinho D, de Bree A, Arnault N, Bertrais S, 
Galan P, Hercberg S. 2004. Consumption of foods rich in 
flavonoids is related to a decreased cardiovascular risk in 
apparently healthy French women. / Nutr 134: 923-926. 

10. Sakai Y, Murakami T, Yamamoto Y. 2003. Antihypertensive 
effects of onion on NO synthase inhibitor-induced hyper- 
tensive rats and spontaneously hypertensive rats. Biosci 
Biotechnol Biochem 67: 1305-131 1. 



11. Kumari K, Augusti KT. 2007. Lipid lowering effect of 
S-methyl cysteine sulfoxide from Allium cepa Linn in high 
cholesterol diet fed rats. / Ethnopharmacol 109: 367-371. 

12. Babu PS, Srinivasan K. 1997. Influence of dietary capsaicin 
and onion on the metabolic abnormalities associated with 
streptozotocin induced diabetes mellitus. Mol Cell Biochem 
175: 49-57. 

13. Kumari K, Mathew BC, Augusti KT. 1995. Antidiabetic and 
hypolipidemic effects of S-methyl cysteine sulfoxide isolated 
from Allium cepa Linn. Indian J Biochem Biophys 32: 49-54. 

14. Kumari K, Augusti KT. 2002. Antidiabetic and antioxidative 
effects of S-methyl cysteine sulfoxide isolated from onions 
(Allium cepa Linn) as compared to standard drugs in alloxan 
diabetic rats. Indian J Exp Biol 40: 1005-1009. 

15. El-Demerdash FM, Yousef MI, El-Naga NI. 2005. Bio- 
chemical study on the hypoglycemic effects of onion and 
garlic in alloxan-induced diabetic rats. Food Chem Toxicol 43: 
57-63. 

16. Campos KE, Diniz YS, Cataneo AC, Faine LA, Alves MJ, 
Novelli EL. 2003. Hypoglycemic and antioxidant effects of 
onion, Allium cepa: dietary onion addition, antioxidant activity 
and hypoglycemic effects on diabetic rats. Int J Food Sci Nutr 
54: 241-246. 

17. Jelodar GA, Maleki M, Motadayen MH, Sims S. 2005. Effect 
of fenugreek, onion and garlic on blood glucose and histo- 
pathology of pancreas of alloxan-induced diabetic rats. Indian 
J Med Sci 59: 64-69. 

18. Sheela CG, Kumud K, Augusti KT. 1995. Anti-diabetic 
effects of onion and garlic sulfoxide amino acids in rats. 
Planta Med 61: 356-357. 

19. Like AA, Rossini AA. 1976. Streptozotocin-induced pan- 
creatic insulities: new model of diabetes mellitus. Science 
193: 415-417. 

20. Jafari MA, Aslam M, Javad K, Singh S. 2000. Effect of Punka 
granatum L. (flowers) on blood glucose level in normal and 
alloxan induced diabetic rats. J Ethnopharmacol 70: 309-314. 

21. Gilman AG, Rail TW, Nies AS, Tayer P. 1990. Goodman and 
Gilman's the pharmacological basis of therapeutics. 8th ed. 
Pergamon Press, New York, NY, USA. p 1317-1322. 

22. Bhushan S. 1984. Effect of oral administration of raw onion 
on glucose tolerance test of diabetics: a comparison with 
tolbutamide. Curr Med Pract 28: 712-715. 

23. Eldin IMT, Ahmed EM, Abd Elwahab HM. 2009. Hypo- 
glycemic activity and regeneration of pancreatic beta-cells 
produced by Allium cepa in alloxan-induced diabetic rats. 
Omdurman Journal of Pharmaceutical 1: 562-568. 

24. Taj Eldin IM, Ahmed EM, Elwahab HMA. 2010. Preliminary 
study of the clinical hypoglycemic effects of Allium cepa (red 
onion) in type 1 and type 2 diabetic patients. Environ Health 
Insights 4: 71-77. 

25. Yeo J, Kang YM, Cho, SI, Jung MH. 2011. Effects of a 
multi-herbal extract on type 2 diabetes. Chin Med 6: 10. 

26. Fonseca SG, Burcin M, Gromada J, Urano F. 2009. 
Endoplasmic reticulum stress in beta-cells and development 
of diabetes. Curr Opin Pharmacol 9: 763-770. 

27. Araki E, Oyadomari S, Mori M. 2003. Impact of endoplasmic 
reticulum stress pathway on pancreatic (3-cells and diabetes 
mellitus. Exp Biol Med 228: 1213-1217. 

28. Kaufman RJ, Back SH, Song B, Han J, Hassler J. 2010. The 
unfolded protein response is required to maintain the 
integrity of the endoplasmic reticulum, prevent oxidative 
stress and preserve differentiation in p-cells. Diabetes Obes 
Metab 1: 99-107. 

29. Ali M, Thomson M, Afzal M. 2000. Garlic and onions: their 
effect on eicosanoid metabolism and its clinical relevance. 
Prostaglandins Leukot Essent Fatty Acids 62: 55-73.