Content uploaded by Salah M. Alchalabi
Author content
All content in this area was uploaded by Salah M. Alchalabi on May 17, 2022
Content may be subject to copyright.
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6787
http://annalsofrscb.ro
Positive effect of Allium sativum and Citrus aurantifolium
plants on glucose level in diabetic rats using Alloxan
Salah M.M. Al Chalabi1 ,Khalid Suhail AL-Azzawi1
1.Biotechnology Research Center / Al-Nahrain University. Baghdad. Iraq
Corresponding: salahchalabi63@gmail.com
Abstract
The current study was designated to investigate the effect of Allium sativum and Citrus
aurantifolium plants (C. aurantifolium ) extract on blood glucose and lipid profile as well as
body weight in diabetic rats, thirty adult rats were divided into five groups (6rat for each). G1
:served as healthy control given tap water G2 :diabetic without treatment , G3: diabetic
treated with garlic extract 150 mg\kg body weight, G4:diabetic treated with C. aurantifolium
and G5: group treated with150 mg\kg mix extracts (garlic and C. aurantifolium).All treated
animals were given orally 1 ml of extracts every day. The effects of aqueous extract of garlic
and C. aurantifolium on some parameters were investigated in normal and diabetic rats such
as fasting blood sugar(FBS), fasting serum insulin(F.serum insulin) ,ketone body , lipid
profile (Cholesterol , Triglyceride, High density lipoprotein( HDL),and Low density
lipoprotein LDL) , the results investigated a significant decrease in glucose levels in group
treated with mix plants(159.73±2.67) as compared with garlic (176.10±2.69) and C.
aurantifolium (205.45±4.09) after twenty days of treatment, also the results display a
significant improvement in insulin level in groups which treated with garlic , C. aurantifolium
and mix plants (4.61±1.22 ,3.69±1.03 and 4.21±1.50 mg\dl respectively) compared with
untreated diabetic group ( 1.88±0. 60), the value of ketone body was decreased in all treated
groups with garlic, C. aurantifolium and mix plants(5.73±1.98, 6.94±2.86 and4.90±1.84)
respectively, the results report a significant decline in cholesterol level in groups treated with
garlic ,C. aurantifolium and mix extract (91±3.98, 95±4.35 and 87±2.45 )mg\dl respectively
compared with the untreated diabetic group (108±3.08 mg\d). the level of Triglyceride
reported a significant p<0.05 decrease in all groups treated with garlic ,C. aurantifolium and
mix extract ( 89±3.96, 90±3.78 and 85±3.73) mg/dl respectively compared with untreated
diabetic group (102±4.43) mg\dl . HDL level revealed significant p<0.05 improvement in
groups treated with garlic ,C. aurantifolium and mix extract(38±2.94, 32±2.09 and 42±3.02)
mg\dl compared with control and untreated diabetic groups (30±2.12 and 24±3.53) mg\dl ,
reduced level of LDL were assessed in groups treated with garlic ,C. aurantifolium and mix
extract(40±3.59, 43±4.50 and30±3.42) mg\dl. There was a significant p<0.05 improvement
in body weight in the group treated with mix plants extract (184 ±4.30 g) after 30 days as
compared with these groups at the beginning of experiment (178 ±2.93) g.
Key word: plant extract, ketone body ,blood glucose
Introduction
Diabetes and its complications consider a major medical problem these complication
include nephropathy, retinopathy, neuropathy, and cardiovascular morbidity [1]. Diabetes
was also the main reason of the new cases of blindness and kidney failure in 2005 in the
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6788
http://annalsofrscb.ro
United States [2], almost 60 to 70 percent of patients with diabetes showed severe
neurological injuries. Controlling diabetes and its complications is still a global problem and
fully successful treatments are yet to be discovered[3]. According to latest studies plant
products have demonstrated wide range of valuable therapeutic activities without causing any
side effects [4]. The major concern in diabetes is increased oxidative stress. Therefore,
dietary supplementation with antioxidants such as vitamins, and flavonoids has been used in
attempts to prevent the occurrence of many diabetes complications by preventing oxidative
damage and protect cells from damage caused by free radical species[5], thus this product
have gained much attention due to their wide spectrum of therapeutic properties as verified
by both in vitro and in vivo studies [6, 7]
Medical plants may have potential roles in the treatment of diabetes and becoming more
popular because these spices show hypoglycemic and antioxidant activities, no side-effects
and synergistic actions[8].Garlic (Allium sativum) is an aromatic herbaceous plant and one of
the oldest and important herbs that have been used from ancient times as traditional medicine
[9,10]. The plant extract have various biological activities and proved to be very important
for human health due to its antioxidant, anticarcinogenic and antimutagenic effects
[11.12].The main function of garlic on diabetes is in maintaining blood sugar level, this herb
can decrease glucose level, the component such as allyl propyl disulfide and allicin in garlic
can be used as antihypertension which reduce the blood pressure and plasma creatinine levels.
Garlic also protects the kidneys from diabetes nephropathy[13.] Allicin have function in
increasing liver metabolism, insulin secretion and controlling lipid peroxidation, it is also
improving the antioxidant status of cells. Thus, garlic is beneficial for the body because it
protects cells from the effects of oxidative stress due to hyperglycemia[14].
Lime (C. aurantifolia), also known as key lime is characterized by pulp poor, thick peel. it
is used in the food and pharmaceutical industries and treatment of several diseases including
fever, obesity and inflammation [15]. Chemical analysis of the extract revealed the presence
of several flavonoids and limonoids [16], extract of lime has been found to inhibit pancreatic
α-amylase activity which lead to reduce hyperglycemia and ameliorate diabetic
complications [17,18]. In recent years actual clinical research investigate the beneficial effect
of lime in regulating the balance and homeostasis of the body in a holistic fashion ,this plant
exhibited many biological activities and pharmacological functions, such as antioxidation
anti-inflammatory and free radical scavenging activity [19,20] .The aim of this current
work was to estimate the effect of Allium sativum and C. aurantifolium plants extract on
blood glucose and lipid profile as well as body weight in diabetic rats..
Materials and methods
1.prepartion of plant extract
About 50 g of dried garlic and 50 g of C. aurantifolium powder were mixed with 250 ml
of the distilled water (for each powder) and kept on a water bath shaker for 24 h at 30 °C., a
filter paper was used to collect filtrate which was used for further experiments.
2. Experimental design
Rats were obtained from biotechnology research center\Al-Nahrain university, thirty adult
rats aged between 4-5 months ,animals were acclimatized for one week and they had free
excess ad libitum to food and water.
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6789
http://annalsofrscb.ro
3. Induction of diabetes
The rats were allowed fasting for 12 hours and induced diabetic by as single dose of
alloxan(Sigma) 100 mg\kg body weight , the level of blood sugar more than 250 mg\dl were
selected for the study. The animals were randomly divided into five groups each containing
six animals, as follow G1: served as control group given tap water, G2;diabetic without
treatment ,G3: diabetic treated with garlic extract 150 mg\kg body weight,G4: diabetic treated
with C.aurantifolium and G5: treated with150 mg\kg mix extracts (garlicand C.
aurantifolium).All treated animals were given orally volume 1 ml \day of extracts for thirty
days.
4.Biochemical analysis
Blood glucose was measured by glucometer (glucose enzymatic colorimetric test kit(Biocon
Diagnostik,Germany).The T.chol concentration was estimated with the using commercially
obtainable kit (bio-Merieux), the value of the cholesterol spectrophotometrically specified at
wave length 500nm.The serum TG was assessed through the use of the enzymatic approach
by using the Bio-Merieux kit. The TG serum concentration has been specified at 500nm.Level
of the HDL-c and LDL were measured with the use of the enzymatic approach by using the
(bio-Merieux) kit and specified spectrophotometrically at wave length 500nm. The ketone
body was measured by using BioAssay\USA, EnzyChromTM Ketone Body Assay Kit
(EKBD-100) and absorbance measured at wave length 340 nanometer.
5. Body Weight
Rats body weights were measured weekly through all the experimental period for all groups.
Initial weight was registered at zero time, and then recorded the final weight at the end of the
experiment after 30 days.
6. Statistical Analysis
The data of the experiment were calculated by using one-way analysis of difference and
the group differences were calculated using Duncan multiple range test, data are presented as
mean± SM, the different big letters investigate a significant difference (P<0.05).
Results
The obtained results in table 1 indicated the presence of Tannin, Saponine, Phenol,
Flavonoids ,Terpenes, and Volatile oil
Table 1: Manual detection of some active compounds in the aqueous extracts of Allium
sativum and C. aurantifolium
Phytochemicadl compoun
Allium sativum
C. aurantifolium
Tannin
+
+
Sap nine
+
-
Phenol
+
+
Flavonoids
+
+
Volatile oil
+
_
terpenes
+
+
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6790
http://annalsofrscb.ro
As shown in table 2 the results of glucose levels significantly increased in untreated diabetic
group(398.21±5.84) at the end of experiment compare with control group(89.33±3.65)and
treated groups with garlic, C.aurantifolium and mix plants(176.10±2.69 ,205.45±4.09
and159.73±2.67) mg\dl respectively. On other hand the results showed a significant decreased
in glucose levels in group treated with mix plants(159.73±2.67) as compared with garlic
(76.10±2.69) and C. aurantifolium (205.45±4.09) after twenty days of treatment. Also the
results display significant improvement in insulin level in groups which treated with garllic,
C.aurantifolium and mix plants (4.61±1.22 ,3.69±1.03 and 4.21±1.50) mg\dl respectively
compared with untreated diabetic group( 1.88±0. 60).The value of ketone body was revealed
significant increase in untreated diabetic group (12.65±3.04) while the value of ketone body
was decreased in all treated gropes included garllic, C.aurantifolium and mix
plants(5.73±1.98, 6.94±2.86 and4.90±1.84) respectively
Table2: The effect of Allium sativum and C.aurantifolium extracts on the level of
glucose. insulin and Ketone body in diabetic rats.
ketone body
Mmool means
±SE
F.s.insulin
uU\ml
means ±SE
FBS mg\dl
means ±SE
F.s.insulin
uU\ml
means ±SE
FBS mg\dl
means ±SE
F.s. insulin
uU\ml
means ±SE
FBS mg\dl
means ±SE
Groups
2.43±0.08
C
4.98±1.63
A
89.33±3.65
E
5.08±1.53
A
91.54±
E
5.74±1.07 A
105.54 ±3.64
E
Control
12.65±3.04
A
1.88±0. 60
C
398.21±5.84
A
2.09±0.65
C
368.06±
A
383.22±5.6
9
B
383.22±5.69
B
Untreated
diabetic
5.73±1.98
B
4.61±1.22
A
176.10±2.69
C
3.66±1.05
B
212.63±
D
2.57±0.97
B
370.53±2.55
C
Diabetic + garlic
150 mg\kg
6.94±2.86
B
3.69±1.03
B
205.45±4.09
B
3.32±1.09
B
265.31±
B
2.34±0.78
B
345.37±4.67
D
Diabetic +C.
aurantifolium
150 mg\kg
4.90±1.84
AB
4.21±1.50
A
159.73±2.67
D
3.87±1.03
B
244.38±
C
2.32±0.83
B
395.12±3.48
A
Diabetic +
garlic+C.
aurantifolium
150 mg\kg
Means having with the different letters in same column differed significantly
There was a significant p<0.05 increase in the level of serum cholesterol in untreated
diabetic group (108±3.08) mg\dl compared with control group ( 85±2.90)mg\dl ,the results
show a significant p<0.05 decline in cholesterol level in groups treated with garlic ,C.
aurantifolium and mix extract (91±3.98, 95±4.35 and 87±2.45 ) mg\dl respectively compared
with the untreated diabetic group (108±3.08) mg\d. The levels of Triglyceride obtained
significant p<0.05 increase in untreated diabetic group(102±4.43) mg\dl compared with
control group( 82±2.65) mg\dl ,while results show significant p<0.05 decreased in
Triglyceride in all groups treated with garlic ,C. aurantifolium and mix extract (989±3.96,
90±3.78 and 85±3.73) mg/dl respectively compared with untreated diabetic group102±4.43
mg\dl . The results of ( HDL) revealed significant p<0.05 improvement in in groups treated
with garlic ,C. aurantifolium and mix extract(38±2.94, 32±2.09 and 42±3.02) mg\dl
compared with control and untreated diabetic groups(30±2.12 and 24±3.53) mg\dl .the results
were revealed significant p<0.05 increased in (LDL) in untreated diabetic group( 55±5.42)
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6791
http://annalsofrscb.ro
and reduced level of LDL in groups which treated with garlic ,C. aurantifolium and mix
extract(40±3.59, 43±4.50 and30±3.42) mg\dl,as shown in table 3
Table3: Effect of Allium sativum and C. aurantifolium extracts on lipid profile.
Groups
Cholesterol
mg\dl means ±SE
Triglyceride
mg\dl means ±SE
HDL
mg\dl means ±SE
LDL
mg\dl means ±SE
Control
85±2.90
C
82±2.65
C
30±2.12
B
44±3.22
B
Untreated (diabetic)
108±3.08
A
102±4.43
A
24±3.53
C
55±5.42
A
Diabetic garlic 150
mg\kg
91±3.98
B
89±3.96
B
38±2.94
A
40±3.59
C
Diabetic C.
aurantifolium+ 150
mg\kg
95±4.35
B
90±3.78
B
32±2.09
B
43±4.50
B
Diabetic C.
aurantifolium+ garlic
150 mg\kg
87±2.45
C
85±3.73
C
42±3.02
A
30±3.42
D
Means having with the different letters in same column differed significantly
Body weight of each rat was investigated at the first day of experiment and the final body
weights were recorded at the end of experiment after 30 days ,there was a significant <0.05
decrease in body weight in untreated diabetic groups156 ± 3.40 compared with the same
animals groups at the beginning of experiment185 ± 4.85 ,also the results show no significant
decrease in body weight for groups treated with garlic and C. aurantifolium (177±3.96
176±4.34respectively after 30 days of treatment compared with the same animals at the first
day(179±4.76 ,181±3.99) g respectively. While body weight show a significant p<0.05
improvement in the group treated with mix plants extract 184 ±4.30 g after 30 days as
compared with these group at the beginning of experiment (178 ±2.93 g,as recorded in table 4
Table4: Effect of Allium sativum and C. aurantifolium extracts on body weight.
Final body weight\gm
means ±SE
Initial body weight\gm
means ±SE
Groups
193 ± 5.88 A
182± 3.44 B
Control
156 ± 3.40 B
185 ± 4.85 A
Untreated diabetic
177±3.96 A
179±4.76 A
Diabetic + garlic 150 mg\kg
178±4.34 A
181±3.99 A
Diabetic+ C.aurantifolium 150 mg\kg
184 ±4.30 A
178 ±2.93 B
Diabetic + garlic+C. aurantifolium
150 mg\kg
Means having with the different letters in same row differed significantly
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6792
http://annalsofrscb.ro
Discussion
The result obtained from this study indicated the presence of Tannin, Sapnine, phenol,
Volatile oil and Terpenes in the aqueous extracts of Allium sativum and C. aurant-
ifolium ( table 1) , The results presented in table2 showed a significant decreased in glucose
levels in group treated with mix plants as compared with garlic and C. aurantifolium after
twenty days of treatment, also the results display a significant improvement in insulin level
in groups which treated with garlic, C. aurantifolium and mix plants compared with untreated
diabetic group, these results might be related to that, Ethanolic extracts of garlic reported an
antidiabetic activity against alloxan-induced diabetic mice by inducing the insulin secretion
from parietal cells of the pancreas [20]. Another clinical work examined the antidiabetic
effect of garlic pills administration in patients with type II diabetes and hyperlipidemia and
they revealed that garlic pills inhibit the fasting blood sugar and cholesterol level [21].
Moreover garlic contain allicin , cysteine sulfoxide, and S-allyl cysteine sulfoxide and these
compounds reduced the level of glucose by several mechanism that include, enhancing the
secretion of insulin from beta cells, increasing the cell sensitivity to insulin and preventing the
insulin activation caused by liver, the activity of allicin in reducing blood glucose in rats was
similar to that investigated by insulin and glibenclamide. Garlic oil also was reported to
decrease the serum alanine transferases ,amylase and aspartate in diabetic rats[22].The
limonene effects include stimulation of insulin secretion ,regeneration of β-ells, amelioration
of secondary complications of higher blood glucose such as hyperlipidaemia via inhibition of
liver x receptors signaling pathway, modulation of transcription factors such as activation of
peroxisome proliferator-activated receptors and modulation of rate limiting enzymes of
carbohydrate metabolism [23,24] , garlic and citrus extract contain flavonoids which have
anti-diabetic effect through their ability to modulate glucose metabolism or insulin sensitivity
at different levels, increase glucose uptake and insulin secretion, and inhibit glucose
production [25]
Also this results could be attributed to the antioxidant vitamins present in garlic and citrus
extract . The mechanism of action could be explained through the ability of the antioxidant
vitamins to scavenge free radicals preventing alloxan-induced oxidative stress and protecting
the β cells. This will consequently increase insulin secretion and decrease elevated blood
glucose levels and lead to decrease ketone body . Plant extracts are known to exert anti-
diabetic activity through enhancing cellular glucose uptake and activation of insulin release
from the pancreatic β-cells [26], the administration of C. aurantifolia oil D-limonene to
hyperglycemic mice and rats caused a significant reduction in blood glucose, triacylglycerol
and cholesterol level, this effect may be due to that D-limenone modulate the glycogen
metabolism in hyperglycemic animals [27].thus our results investigated that both plant
extract is good strategy for decreasing blood glucose when act synergicelly.
According to the results presented in table 3 there was a significant p<0.05 decreased in ,
cholesterol, Triglyceride,HDL,LDL level in groups treated with garlic ,C. aurantifolium and
mix extract compared with the untreated diabetic group. Garlic can improve metabolic
syndrome such as hypercholesterolemia and hypertension, the ability of garlic in reducing
lipid peroxidation is through mechanism of reducing levels of malondialdehyde, this resulting
a protection of heart blood vessels from damage due to oxidative stress [28].The mechanism
for reducing blood cholesterol by garlic is related to that garlic contained vitamin C
(ascorbic acid) which have the ability to destroy existing plaques by binding to lipoproteins
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6793
http://annalsofrscb.ro
and expelling them from the body, increasing vessel elasticity blood by building collagen,
prevent endothelial damage that normally initiates inflammatory responses, also garlic contain
niacin (nicotinic acid) that can reduce cholesterol and LDL levels by inhibition of free fatty
acid flow from adipose tissue and suppression the activity of the lipoprotein lipase enzyme,
reduction fat mobilization and VLDL production in the liver. Furthermore garlic have the
ability to inhibit enzyme 3- hydroxy-3-methylglutaril coenzyme (HMG-CoA) reductase by
binding to the SH group which is a functional part of coenzyme, so that, there is direct
inhibition of the enzyme and suppression of cholesterol synthesis [29]
Menichini et al. (2011) accredited the potential of citrus peel extract in plasma triglyceride
reduction to the ability of citrus flavonoids to prevent conjugation between triglycerides and
oleic acid ,thus leading to an overall decrease in cholesterol level. The citrus flavonoids
decrease free fatty acids and increase fecal excretion of triglycerides, bioactive materials in
citrus extract trigger the activation of receptor cells that incorporate excess triglycerides and
LDL into the liver rather than circulating in the vascular system to form plaque [30],also the
polyphenol compounds in the citrus extract are powerful plasma lipid lowering agents by
increasing the antioxidant activity and by modulating hepatic HMG-CoA levels, possibly by
binding bile acids and increasing the turnover rate of blood and liver cholesterol [31]. The
present result investigated the beneficial and important effects of garlic and C. aurantifolium
in the health sciences as it opens new felids in drug synthesis and treatment of diabetes.
Several studies may examine the effect of garlic extract on obesity by decreasing the
synthesis of fatty acid [32,33], garlic contains multiple organosulfur compounds which have
anti-obesity properties. Thiacremonone is sulfur compound isolated from garlic that has an
effect on adipocyte cell which lead to decreasing body weight [34,35].The C.
aurantium extract was demonstrated to enhance metabolic rate ,energy expenditure and to
promote weight loss when given for six to 12 weeks [36], the extracts from peels citrus could
prevent the development of obesity through the modulation of lipid and glucose metabolism.
It is investigated that polyphenols considerably inhibited the fat accumulation,
hyperlipidemia, high blood glucose levels and insulin resistance, weight gain which are
different aspects of obesity [37], but our result indicated an improvement in body weight in
groups treated with mix extract (table 4), this may be attributed to difference in study design
and other mechanism that not fully understand.
Conclusion
From the results obtained in this present work, it could be safely concluded that both garlic
and C.aurantifolia extract be useful in formulating strategies for therapeutic of hyperglycemia
and diabetic complication.
Refrenses
1.R. G. Sathiyabama, G. Rajiv Gandhi, M. Denadai et al.,(2018) “Evidence of insulin-dependent signalling
mechanisms produced by Citrus sinensis (L.) Osbeck fruit peel in an insulin resistant diabetic animal
model,” Food and Chemical Toxicology, vol. 116, Part B, pp. 86–99.
2. Habibzadeh H, Sofiani A, Alilu L, Gillespie M. (2017). The Effect of Group discussion-based Education
on Self-management of Adults with Type 2 Diabetes Mellitus Compared with Usual Care: A
Randomized Control Trial. Oman Med J.;32:499-506.
3.Malviya, N., Jain, S., and Malviya, S.,( 2010). Antidiabetic potential of medicinal
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6794
http://annalsofrscb.ro
plants. Acta poloniae pharmaceutica, 67 (2), 113–118
4.D. J. Newman and G. M. Cragg, .,(2016) “Natural products as sources of new drugs from 1981 to
2014,” Journal of Natural Products, vol. 79, no. 3, pp. 629–661.
5. PELUSO M.R. .,(2006) Flavonoids attenuate cardiovascular disease, inhibit phosphodi-esterase and
modulate lipid homeostasis in adipose tissue and liver. Exp Biol Med (Maywood); 231 (8): 1287 – 99.
6.L. Liu, D. Tang, H. Zhao, X. Xin, and H. A. Aisa, .,(2017) “Hypoglycemic effect of the polyphenols rich
extract from Rose rugosa Thunb on high fat diet and STZ induced diabetic rats,” Journal of
Ethnopharmacology, vol. 200, pp. 174–181
7.A. C. de Camargo, M. A. B. Regitano-d’Arce, A. C. T. Biasoto, and F. Shahidi, .,(2014) “Low molecular
weight phenolics of grape juice and winemaking byproducts: antioxidant activities and inhibition of
oxidation of human lowdensity lipoprotein cholesterol and DNA strand breakage,” Journal of
Agricultural and Food Chemistry, vol. 62, no. 50, pp. 12159–12171.
8. Panda A, Jena S, Sahu PK, Nayak S, Padhi P. (2013). Effect of polyherbal mixtures on the treatment of
diabetes. ISRN Endocrinol.
9. Ayaz, E.; Alposy, H.C. .,(2007) . Garlic (Allium sativum) and traditional medicine. Turkiye Parazitolojii
Derg. 31, 145–149.
10. Badal, D.S.; Dwivedi, A.K.; Kumar, V.; Singh, S.; Prakash, A.; Verma, S.; Kumar, J. .,(2019) . Effect of
organic manures and inorganic fertilizers on growth, yield and its attributing traits in garlic (Allium
sativum L.). J. Pharmacogn. Phytochem. 8, 587–590.
11.Corzo-Martínez MCN.(2007). Biological properties of onions and garlic. Trends Food Sci Technol.
18(12):609–625.
12.Santhosha SG, Jamuna P, Prabhavathi SN. .(2013). Bioactive components of garlic and their
physiological role in health maintenance: A review. Food Biosci.;3(2013):59–74.
13. Buendía HA, González AT, Reyes S, Arroyo OG, García A, Tapia R, et al .(2018). Immuno-modulatory
effects of the neutraceutical garlic derivative allicin in the progression of diabetic nephropathy. Int J
Mol Sci.;19(10):3107.
14. Suleria HAR, Butt MS, Khalid N, Sultan S. .(2015). Garlic (Allium sativum): diet based therapy of 21st
century - a review. Asian Pacific J Trop Dis.;5(4):271- 8.
15.NE Sandoval-Montemayor, A García, E Elizondo-Treviño, E Garza-González, L Alvarez, and M Del
Rayo Camacho-Corona, .(2012). Chemical composition of hexane extract of Citrus aurantifolia and
anti-Mycobacterium tuberculosis activity of some of its constituents, Molecules, Vol. 17, , pp. 11173-
84.
16.JR Patil, KN Chidambara Murthy, GK Jayaprakasha, MB Chetti, and BS Patil,(2009). Bioactive
compounds from Mexican lime (Citrus aurantifolia) juice induce apoptosis in human pancreatic cells, J
Agric Food Chem, Vol. 57, pp. 10933-42.
17.G Şeker Karatoprak, ÇY Aşık, A Çakır, and EK Şafak,(2020). In vitro pharmacological screening of
antioxidant, cytotoxic and enzyme inhibitory activities of Citrus aurantifolia Linn. Dried fruit extract,
Int J Environ Health Res, , pp. 1-10.
18.H Mawarti, Khotimah, M Zulfikar As’ad, and M Rajin,(2018). Ameliorative effect of Citrus aurantifolia
and Cinnamomum burmannii extracts on diabetic complications in a hyperglycemic rat model, Trop J
Pharm Res, Vol. 17, pp. 823-9.
19. Suntar I, Khan H, Patel S, Celano R, Rastrelli L.(2018). An Overview on Citrus aurantium L.: Its
Functions as Food Ingredient and Therapeutic Agent. Oxidative medicine and cellular
longevity. ;2018:7864269.
20. Patel, D.K.; Prasad, S.K.; Kumar, R.; Hemalatha, S. .(2012). An overview on antidiabetic medicinal
plants having insulin mimetic property. Asian Pac. J. Trop. Biomed, 2, 320–330.
21. Faroughi, F.; Mohammad-Alizadeh Charandabi, S.; Javadzadeh, Y.; Mirghafourvand, M. .(2018). Effects
of garlic pill on blood glucose level in borderline gestational diabetes mellitus: A triple blind,
randomized clinical trial. Iran. Red. Crescent Med. J., 20, e60675.
22. Zhai, B.; Zhang, C.; Sheng, Y.; Zhao, C.; He, X.; Xu, W.; Huang, K.; Luo, Y .(2018). Hypogly-cemic
and hypolipidemic effect of S-allyl-cysteine sulfoxide (alliin) in DIO mice. Sci. Rep., 8, 3527.
Annals of R.S.C.B., ISSN:1583-6258, Vol. 25, Issue 4, 2021, Pages. 6787 – 6795
Received 05 March 2021; Accepted 01 April 2021.
6795
http://annalsofrscb.ro
23. Murali R, Saravanan R. .(2012). Antidiabetic effect of d-limonene, a monoterpene in streptoz-otocin-
induced diabetic rats. Biomedicine & Preventive Nutrition.;2(4):269-75..
24. Jing L, Zhang Y, Fan S, Gu M, Guan Y, Lu X, et al. (2013). Preventive and ameliorating effects of
citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity.
European journal of pharmacology.;715(1):46-55
25.Alkhalidy, H., Wang, Y., Liu, D. (2018). Dietary flavonoids in the prevention of T2D: An overview.
Nutrients, 10. A
26.Gushiken, L. F., Beserra, F. P., Rozza, A. L., Bérgamo, P. L., Bérgamo, D. A., Pellizzon, C. H. (2016).
Chemical and biological aspects of extracts from medicinal plants with antidiabetic effects. Rev.
Diabet. Stud., 13, 96–112.
27.Ibrahim FA, Usman LA, Akolade JO, Idowu OA, Abdulazeez AT, Amuzat AO. (2019). Antidiabetic
potentials of Citrus aurantifolia leaf essential oil. Drug Res (Stuttg). 69:201–206.
28. Naderi R, Mohaddes G, Mohammadi M, Alihemmati A, Badalzadeh Z.(2011). On oxidative stress and
histopathology of cardiac tissue in streptozotocin-induced diabetic rats.;102(4):380-90.
29.Brajawikalpa R S and Kautama M G.(2018). Pengaruh pemberian ekstrak etanol bawang putih terhadap
kadar kolesterol total , LDL dan HDL pada tikus putih hiperkolesterol
30.Menichini, F., Loizzo, M. R., Bonesi, M., Conforti., De Luca, D., Statti, G. A., Tundis, R. (2011).
Phytochemical profile, antioxidant, anti-inflammatory and hypoglycemic potential of hydroalcoholic
extracts from Citrus medicca L. cv Diamante flowers, leaves and fruits at two maturity stages. Food
Chem. Toxicol., 49, 1549–1555.
31. Marounek, M., Volek, Z., Synytsya, A and Copíková, J. (2007). Effect of Pectin and Amidated Pectin on
Cholesterol Homeostasis and Cecal Metabolism in Rats Fed a HighCholesterol Diet. Physiological
Research, 56(4):433-42.
32. Lee, M.-S., Cho, S.-M., Lee, M.-H., Lee, E.-O., Kim, S.-H., &Lee, H.-J. (2016) .Ethanol extract of Pinus
koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by
activating adenosine monophosphateactivated protein kinase (AMPK). BMC Complement Altern Med.
16, 51.
33. Jayarathne, S., Koboziev, I., Park, O.-H., Oldewage-Theron, W.,Shen, C.-L., & Moustaid-Moussa, N.
(2017) .Anti-inflammatory and anti-obesity properties of food bioactive mponents:effects on adipose
tissue. Prev Nutr Food Sci. 22, 251.
34. Kim, E.J., Lee, D.H., Kim, H.J., Lee, S.J., Ban, J.O., Cho, M.C.,Jeong, H.S., Yang, Y., Hong, J.T., &
Yoon, D.Y. (2012) .Thiacremonone,a sulfur compound isolated from garlic, attenuates lipid
accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes. J Nutr Biochem. 23,
1552–1558.
35. Lee, M.S., Kim, I.H., Kim, C.T., & Kim, Y. (2011) .Reduction of body weight by dietary garlic is
associated with an increase in uncoupling protein mRNA expression and activation ofAMP-activated
protein kinase in diet-induced obese mice. J .Nutr. 141, 1947–1953.
36.S. J. Stohs, H. G. Preuss, and M. Shara,(2012). “A review of the human clinical studies involving Citrus
aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine,” International Journal of
Medical Sciences, vol. 9, no. 7, pp. 527–538
37.Umashanker M, Shruti S. (2011) .Traditional Indian herbal medicine used as antipyretic, antiulcer, anti-
diabetic and anticancer: A review. Int J Res Pharm Chem 1: 1152-1159.
