Research Article
Urtica dioica Effect on Malonyl-CoA Decarboxylase
Durdi Qujeq 1,2 * , Mohsen Tatar 2, Farideh Feizi 3, Hadi Parsian 1,2, Sohrab Halalkhor 2
1
Cellular and Molecular Biology Research Center, Department of
Biochemistry and Biophysics, Faculty of Medicine, Babol University of
Medical Sciences, Babol, IR Iran
2 Department of Biochemistry and Biophysics, Faculty of Medicine, Babol University of Medical Sciences, Babol, IR Iran
3 Department of Anatomical Sciences, Faculty of Medicine, Babol University of Medical Sciences, Babol, IR Iran
*Corresponding
author: Durdi Qujeq, Cellular and Molecular Biology Research Center,
Department of Biochemistry and Biophysics, Faculty of Medicine, Babol
University of Medical Sciences, Babol, IR Iran. Tel: +98-1112229591-5,
Fax: +98-1112226109, Email: d.qujeq@mubabol.ac.ir
Abstract
Background: The malonyl-CoA decarboxylase (MCD, EC.4.1.1.9) enzyme regulates malonyl-CoA levels. The effect of aerial parts extracts of Urtica dioica (UD) on MCD is poorly understood.
Objectives: The present experiment was undertaken to evaluate the effect of UD aerial parts extracts on MCD level.
Materials and Methods: In
this experimental study, two groups of rats were used: normal and
hyperglycemic group. Then UD aerial parts extracts (5 mg /500 µL)
administrated to the hyperglycemic group of rats and finally, the MCD
and insulin levels were measured in both groups.
Results: Interestingly,
we observed that the UD aerial parts extracts powder caused a
significant (P < 0.05) increase in insulin level during the
experiment, from the base level of 0.36 ± 0.07 μg/L to the peak value of
0.52 ± 0.15 μg/L. Also, it caused a significant (P < 0.05) decrease
in MCD level, from the base level of 29.68 ±1.29 pg/mL to the bottom
value of 22.12 ± 2.41 pg/mL.
Conclusions: The results of the present study indicate that UD aerial part extracts would decrease MCD level in hyperglycemic rats.
Keywords: Urtica dioica; Malonyl Coenzyme A Decarboxylase; Streptozotocin
1. Background
Malonyl-CoA is not only a key intermediate for fatty acid synthesis, but also a key metabolic sensor (1). Much evidence has accumulated in recent years, indicating that malonyl-CoA is a cytosolic signal of glucose abundance (2, 3). Earlier studies also indicated that MCD could be an important site for intervention in diabetic status (3). Many studies showed that MCD is ubiquitously distributed in all organisms (4).
The enzyme malonyl-CoA decarboxylase (MCD, EC 4.1.1.9) catalyzes the conversion of malonyl-CoA to acetyl-CoA (4, 5). Furthermore, MCD balances the energy intake and expenditure (6). According to the literature, Urtica dioica has been known as a medicinal plant (7). Previous studies have also demonstrated that U. dioica is known for its antidiabetic effects in folk medicine (8-10).
Several experimental studies revealed that UD possesses hypoglycemic properties (11). Alcoholic and aqueous extracts of UD leaf can repair pancreatic tissue in streptozotocin-induced diabetic models (12). UD leaves extracts (given parenterally) possess a hypoglycemic effect on alloxan hyperglycemic rats (13). UD affects on the liver enzymes activity (14). Preliminary studies revealed that UD administration could prevent atherosclerosis by protecting liver enzymes (15). UD is shown to prevent low density lipoprotein (LDL) oxidation and has an antihypotensive effect (16).
Despite
this knowledge about UD, there is little information about the effect
of UD aerial parts extracts on MCD level. Given the above findings, it
is worthwhile to study the possible effect of UD aerial parts extracts
on MCD level. Based on the mentioned studies, we proposed the following
hypothesis that administration of UD aerial parts extracts might
contribute to the control of MCD.
2. Objectives
This study aimed to evaluate the effect of UD aerial parts extracts on MCD level.
3. Materials and Methods
3.1. Urtica dioica Aerial Parts
Urtica dioica aerial parts were collected from Babol City,
Iran. The aerial parts were isolated and dried at laboratory
temperature (20-25°C) in shadow and then were grounded into powder as
described by Qujeq et al. (12, 17).
3.2. The Aqueous and Ethanolic Extract of Aerial Parts of Urtica dioica
In order to prepare the aqueous and ethanolic extract of the aerial parts of Urtica dioica, we used the methods as described by Qujeq et al. (12, 13, 17).
3.3. Isolation and Purification of Aerial Parts of Urtica dioica Extracted by Chromatography
One-tenth gram of crude extract was loaded onto the column
chromatography. The whole fractions were collected and used in the next
steps. Urtica dioica aeri administration dose was 5 mg / 500 µL.
3.4. Animals
Male adult Wistar rats (n = 12) weighting between 180 to 225 g
were used. The rats were divided into two groups: control group and
hyperglycemic group. All protocols involving animals were approved by
Babol University Animal Care and Use Committee. All experimental
manipulations were carried out with the animal under ether inhalation
anesthesia.
3.5. Induced Hyperglycemic Status
Streptozotocin (STZ) was dissolved in cold 0.9% saline solution
just before use and injected intraperitoneally (IP) to the rats as
described by Qujeq et al. (12, 17, 18).
Hyperglycemic state was induced by a single IP injection of STZ (120
mg/kg body weight) to overnight fasted rats. Hyperglycemic state was
confirmed by measuring the glucose concentration using a kit.
3.6. Experimental Design
A total amount of 5 mg / 500µL of aerial parts of Urtica dioica was
administrated IP to hyperglycemic rats. At the end of the experiment,
blood samples were collected and biochemical factors were assayed by the
spectrophotometric method.
3.7. Experimental Procedure
Blood glucose level was determined by using a glucose kit
(Jenway, Model 6505, UK, Pars Azmon Co., Tehran, Iran). Insulin level
was measured by an enzyme immunoassay ELISA kit specific for rats made
by Mercodia Rat insulin ELISA (10-1250-01, Mercodia AB, Uppsala,
Sweden). The malonyl-CoA decarboxylase level was determined by ELISA
method using a rat malonyl-CoA decarboxylase (MCD) ELISA kit
(CSB-E11337r, Cusabio Biotech Co. LTD) as previously described (17, 18).
3.8. Statistical Analysis
Data have been presented as mean ± standard error. All tests were
carried out in triplicate. Statistical analysis were done using SPSS
version 18.0. The significance of differences between the mean values
was determined by analysis of variance, and a P value of less than 0.05
was considered statistically significant.
4. Results
Aerial parts of UD
extract increased insulin secretion compared to the untreated
hyperglycemic group (0.52 ± 0.15 vs. 0.36 ± 0.07 µg/L, [P < 0.05]) (Figure 1).
By administration of UD aerial parts extracts, MCD level was reduced
compared to the untreated hyperglycemic group (22.12 ± 2.41 vs. 29.68 ±
1.29 pg/mL, [P < 0.05]). According to our findings, UD aerial parts
extracts can increase insulin secretion. The results of the present
study indicate that UD aerial parts extracts decrease MCD level in the
animals made hyperglycemic with STZ (Figure 2).
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Figure 1.
Serum Insulin Level (µg/L) With Administration of Urtica dioica Aerial Parts Extracts
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Figure 2.
Serum MCD Level (pg/mL) With Administration of Urtica dioica Aerial Parts Extracts
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5. Discussion
In hyperglycemic rats
treated with UD aerial parts extracts, we observed a decrease in MCD
level and increase in insulin level. Our data suggest that MCD can be
targeted for the treatment of hyperglycemic state. This phenomenon is
very important, because at cellular level, malonyl-CoA is a key factor
in energy homeostasis (19).
On
the other hand, MCD plays a key role in the balance of energy intake
and expenditure through the regulation of malonyl-CoA and acetyl-CoA
levels in the cellular metabolism. Malonyl-CoA is a signal for glucose
content, which regulates fuel partitioning and metabolic signal
transduction. Also, malonyl-CoA has been considered as an important site
of intervention in a hyperglycemic state.
Generally, in
situations where MCD level is elevated, the malonyl-CoA content is low,
which results in elevated rates of fatty acid oxidation. In this regard,
growing scientific and medical data supports the fact that MCD
inhibitor decreases the pancreatic malonyl-CoA level (15).
Interestingly,
our results showed that it may be possible to develop therapies for
hyperglycemic state by changing malonyl-CoA levels (with plant materials
effect on MCD).Our study provided the evidence that UD aerial parts
extract regulated MCD level in hyperglycemic rat. While there has been
great interest in the using activator or inhibitor of MCD as a highly
selective tool, but the effects of such agents on insulin release from
pancreatic tissue are disputed.
Many investigators reported that UD aerial parts extract has hypoglycemic activity and β-cell regenerative potency (20). Investigators showed that UD aerial parts extract was a potent stimulator of insulin release from β-cells (21). On the other hand, our findings are in contrast to the previous study (22),
regarding nohypoglycemic activity of aqueous extract of UD. Our results
indicated that increased insulin level by UD aerial parts extracts
might be due to the regeneration in the β-cells.
This switch in
energy substrate improves pancreatic function during hyperglycemia,
suggesting that pharmacological inhibition of MCD may be a novel
approach into treating hyperglycemia (23).
However, other pancreatic mechanisms such as enhanced glucose transport
into the cells, and inhibition of the endogenous glucose production
cannot be rolled out. Therefore, administration of UD aerial parts
extracts after inducing hyperglycemia in rats could increase insulin.
We provided the evidence of UD aerial parts extracts in the control of
MCD level in hyperglycemic rats. Our data demonstrated that UD aerial
parts extracts decrease MCD level. Our data also indicated that MCD
inhibition may accelerate glucose oxidation, and improves functional
recovery in hyperglycemic rat. Insulin is important in hyperglycemic
activity of UD.
This can be considered as one of the mechanisms by
which this extract can regulate the glucose homeostasis. The effect of
MCD requires further evaluation; our data suggest that pharmacological
inhibition of MCD may be a viable approach to the treatment of clinical
pathologies associated with hyperglycemia. However, this result does not
exclude the other involved mechanisms. The biochemical relevance of
these findings is unclear and need to clarify.
Acknowledgments
We would like to thank Mr. Shikhzadeh for his excellent technical assistance.
Footnotes
References
-
1.
Saha
AK, Ruderman NB. Malonyl-CoA and AMP-activated protein kinase: an
expanding partnership. Mol Cell Biochem. 2003;253(1-2):65-70. [PubMed]
-
2.
McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase
system. From concept to molecular analysis. Eur J Biochem. 1997;244(1):1-14. [PubMed]
-
3.
Voilley N, Roduit R, Vicaretti R, Bonny C, Waeber G, Dyck JR, et al.
Cloning and expression of rat pancreatic beta-cell malonyl-CoA
decarboxylase. Biochem J. 1999;340 ( Pt 1):213-7. [PubMed]
-
4.
Zhou
D, Yuen P, Chu D, Thon V, McConnell S, Brown S, et al. Expression,
purification, and characterization of human malonyl-CoA decarboxylase. Protein Expr Purif. 2004;34(2):261-9. [DOI] [PubMed]
-
5.
FitzPatrick DR, Hill A, Tolmie JL, Thorburn DR, Christodoulou J. The
molecular basis of malonyl-CoA decarboxylase deficiency. Am J Hum Genet. 1999;65(2):318-26. [DOI] [PubMed]
-
6.
Folmes CD, Lopaschuk GD. Role of malonyl-CoA in heart disease and the
hypothalamic control of obesity. Cardiovasc Res. 2007;73(2):278-87. [DOI] [PubMed]
-
7.
Gunther RT. The Greek Herbal of Dioscorides.
NewYork: Hafner Publishing; 1959.
-
8.
Petlevski R, Hadzija M, Slijepcevic M, Juretic D, Petrik J. Glutathione
S-transferases and malondialdehyde in the liver of NOD mice on
short-term treatment with plant mixture extract P-9801091. Phytother Res. 2003;17(4):311-4. [DOI] [PubMed]
-
9.
Burrowes JD, Van Houten G. Herbs and dietary supplement use in patients
with stage 5 chronic kidney disease. Nephrol Nurs J. 2006;33(1):85-8. [PubMed]
-
10.
Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian anti-diabetic
plants attenuate progression of renal damage in streptozotocin induced
diabetic mice. J Ethnopharmacol. 2001;76(3):233-8. [PubMed]
-
11.
Newall CA, Anderson LA, Phillipson
JD. Herbal medicines: a guide for health-care professionals.
London: The pharmaceutical press; 1996. p. 201-2.
-
12.
Qujeq D, Tatar M, Feizi F, Parsian H, Sohan Faraji A, Halalkhor S.
Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the
Number and the Diameter of the Islets in Diabetic Rats. Int J Mol Cell Med. 2013;2(1):21-6. [PubMed]
-
13.
Qujeq D, Davary S, Moazzi Z, Mahjoub S. Effect of Urtica dioica leaf
extract on activities of nucleoside diphosphate kinase and acetyl
coenzyme, a carboxylase, in normal and hyperglycemic rats. Afr J Pharm Pharmacol. 2011;5:792-6.
-
14.
Ozen
T, Korkmaz H. Modulatory effect of Urtica dioica L. (Urticaceae) leaf
extract on biotransformation enzyme systems, antioxidant enzymes,
lactate dehydrogenase and lipid peroxidation in mice. Phytomedicine. 2003;10(5):405-15. [DOI] [PubMed]
-
15.
Kanter M, Meral I, Dede S, Gunduz H, Cemek M, Ozbek H, et al. Effects of
Nigella sativa L. and Urtica dioica L. on lipid peroxidation,
antioxidant enzyme systems and some liver enzymes in CCl4-treated rats. J Vet Med A Physiol Pathol Clin Med. 2003;50(5):264-8. [PubMed]
-
16.
Domola MS, Vu V, Robson-Doucette CA, Sweeney G, Wheeler MB. Insulin
mimetics in Urtica dioica: structural and computational analyses of
Urtica dioica extracts. Phytother Res. 2010;24 Suppl 2:S175-82. [DOI] [PubMed]
-
17.
Qujeq D, Tatar M, Feizi F, Parsian H, Halalkhor S. Effects of Teucrium
polium aerial parts extracts on Malonyl-CoA decarboxylase level. Mol Biol Res Commun. 2013;2(4):101-7.
-
18.
Qujeq D, Tatar M, Feizi F, Parsian H, Halalkhor S. Effects of Teucrium
polium leaf extracts on AMPK level in isolated rat pancreases. Res Mol Med. 2013;1(3):32-28.
-
19.
Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased malonyl-CoA
levels in muscle from obese and type 2 diabetic subjects lead to
decreased fatty acid oxidation and increased lipogenesis;
thiazolidinedione treatment reverses these defects. Diabetes. 2006;55(8):2277-85. [DOI] [PubMed]
-
20.
Kavalali G, Tuncel H, Goksel S, Hatemi HH. Hypoglycemic activity of
Urtica pilulifera in streptozotocin-diabetic rats. J Ethnopharmacol. 2003;84(2-3):241-5. [PubMed]
-
21.
Farzami B, Ahmadvand D, Vardasbi S, Majin FJ, Khaghani S. Induction of
insulin secretion by a component of Urtica dioica leave extract in
perifused Islets of Langerhans and its in vivo effects in normal and
streptozotocin diabetic rats. J Ethnopharmacol. 2003;89(1):47-53. [PubMed]
-
22.
Roman Ramos R, Alarcon-Aguilar F, Lara-Lemus A, Flores-Saenz JL.
Hypoglycemic effect of plants used in Mexico as antidiabetics. Arch Med Res. 1992;23(1):59-64. [PubMed]
-
23.
Tang
H, Yan Y, Feng Z, de Jesus RK, Yang L, Levorse DA, et al. Design and
synthesis of a new class of malonyl-CoA decarboxylase inhibitors with
anti-obesity and anti-diabetic activities. Bioorg Med Chem Lett. 2010;20(20):6088-92. [DOI] [PubMed]