A Systematic Review of Efficacy and Safety of Urtica dioica in the Treatment of Diabetes
This review focuses on the efficacy and safety of Urtica dioica which has been utilized in traditional medicine for management of diabetes. All relevant databases including Pubmed, Google Scholar, Web of Science, Scopus, Iranmedex and MD Consult were searched for the terms diabetes mellitus and Urtica dioica without limitation up to 15th September 2010. All the animal studies with the outcome of change in blood glucose or other relevant complications of diabetes and all available abstracts were included. Review articles and letters to the editor were excluded. Search of databases resulted in 724 articles which 87 were potentially relevant studies on Urtica dioica and diabetes. On the basis of inclusion/exclusion criteria, 21 studies were finally included. One human and 20 animal studies were reviewed for the efficacy of Urtica dioica. Most of these studies showed significant decrease in blood glucose and complications of diabetes by use of Urtica dioica. Urtica dioica can affect both pancreatic and extra pancreatic pathways. Available evidences suggest that Urtica dioica can be used to treat diabetes and its long-term complications. Of course, further experiments would help determine exact mechanisms of action, effects and side effects of this herbal medicine.
Received: November 15, 2010;
Accepted: November 24, 2010;
Published: March 16, 2011
Diabetes is one of the most common chronic diseases in the world. The number
of people with diabetes is increasing dramatically due to population growth,
aging, urbanization, and increasing prevalence of obesity and physical inactivity
that is finally associated with major health and socio-economic problems. The
extent and severity of these problems are reflected in extra mortality and at-risk
people. For example, according to the last International Diabetes Federation
(IDF) report, about 2566000 people (6% total population) are suffering from
diabetes in Iran and its prevalence is increasing like other developing countries
expecting to reach 5114900 in 2025 (Sicree et al.,
2007). Current estimates demonstrate that the world prevalence of diabetes
will increase to 7.7% (439 million) adults by 2030. Between 2010 and 2030, there
will be a 69% increase in number of diabetic patients in developing countries
and 20% in developed countries (Shaw et al., 2010).
So, with regard to the issue of socioeconomic burden of diabetes, discovery
of more effective and less side effect therapies are necessary. In the recent
years good data have been obtained from traditional medicines indicating usefulness
of many herbal medicines (Hasani-Ranjbar et al.,
2008, 2009). For a very long time, plants have been
an important role part of treatment of many diseases. The use of plants to treat
diabetes is a centuries-old practice. More than 400 traditional plant treatments
for diabetes have been recorded, but only a small number of these have received
scientific and medical evaluation to assess their efficacy. Hypoglycemic action
from some treatments has been confirmed in animal models, and various hypoglycemic
compounds have been identified. Traditional treatments may provide valuable
clues for the development of new oral hypoglycemic agents and simple dietary
adjuncts. Urtica dioica (Stinging Nettle) has been used for centuries
for food and medical purposes. The genus name Urtica comes from the Latin verb
urere, meaning to burn because of stinging hairs of the herb. The species name
dioica means two houses because the plant usually contains either male or female
flowers. It is abundant in North America, Northern Europe and most of Asia,
usually found in the rural area. It contains flavonoides (0.7-1.8%), silicic
acid (1-4%), potassium-ions (0.6%), nitrates (1.5-3%), volatile oil, histamine,
serotonin, acetylcholine, formic acid and leukotrienes (LTB4, LTC4, LTD4). The
blood sugar lowering effect of Urtica dioica has been mentioned in old
script such as those written by Avicenna. There have been other reports indicating
the benefits of using the infusion or the extract of the leaves or other parts
of this plant for the use in diabetes (Ramos et al.,
1992; Swanston-Flatt et al., 1989). Moreover,
it is used internally and externally as supportive therapy for prostatic hyperplasia
(Hirano et al., 1994; Krzeski
et al., 1993; Kayser et al., 1995),
inflammation (Obertreis et al., 1996), rheumatoid
arthritis, hypertension and allergic rhinitis (Mittman,
The present systematic review aimed to evaluate the efficacy and safety of Urtica dioica in diabetes by reviewing all animal and human studies.
MATERIALS AND METHODS
Databases of Pubmed, Google Scholar, Web of Science, Scopus, Iranmedex, and
MD Consult were searched up to 15th September 2010, for studies examined Urtica
dioica in prevention or treatment of diabetes. The search terms were diabetes
and Urtica dioica without limiting search elements. A Flow diagram of
the search process has been shown in Fig. 1. Among the studies,
there were only one human study and the rest of them were animal ones. All of
animal studies with the outcome of change in blood glucose and other relevant
complications of diabetes with available abstracts were included.
||Flow diagram of the search process.*There was one study which
had both in vivo and in vitro sections. **There was one study
which had both animal and human parts
Review articles and letters to the editor were examined to ensure inclusion
of all relevant studies. Unpublished data such as dissertations were not included.
Two reviewers independently examined the title, abstract and references of each
article to eliminate duplication. The reference lists of articles were also
reviewed for additional relevant studies. The reviewers summarized data on Urtica
dioica for dose, treatment duration, grouping, main outcome, probable mechanism
and side effects (Table 1).
The electronic database search identified 724 articles which 87 were potentially
relevant studies on Urtica dioica and diabetes. Finally, based on our
inclusion and exclusion criteria, 21 studies were included (Table
1) (Ramos et al., 1992; Swanston-Flatt
et al., 1989; Said et al., 2008;
Bnouham et al., 2010; Bnouham
et al., 2003; Bijan et al., 2003;
Petlevski et al., 2001; Shahraki
et al., 2009; Fathi-Azad et al., 2005;
Khouri and Golalipour, 2006; Golalipour
et al., 2009a; Golalipour et al., 2010;
Gunes et al., 1999; Neef
et al., 1995; Jahanshahi et al., 2009;
Fazeli et al., 2008; Fazeli
et al., 2010; Golalipour et al., 2007a;
Golalipour and Khouri, 2007b; Petlevski
et al., 2003; Golalipour et al., 2009b).
Only one human study was found which applied Urtica dioica in combination
with Juglans regia L. Olea europea L. and Atriplex halimus
L. in the form of Glucolevel tablets. This study revealed that acceptable glucose
level was achieved in patients treated with Glucolevel (Said
et al., 2008). Besides, animal studies showed significant decrease
in blood glucose after treatment with Urtica dioica (Said
et al., 2008; Bnouham et al., 2010;
Bnouham et al., 2003; Bijan
et al., 2003; Petlevski et al., 2001;
Shahraki et al., 2009; Fathi-Azad
et al., 2005; Golalipour et al., 2009a;
Golalipour and Khouri, 2007b). One animal study showed
ineffectiveness of Urtica dioica in treated animals (Khouri
and Golalipour, 2006) and another study showed that Urtica dioica
can aggravate diabetes (Swanston-Flatt et al., 1989).
One animal study showed that the active component of Urticadioica can
increase insulin content of blood in normal and streptozotocin-induced diabetes
(Bijan et al., 2003). A suggested mechanism for
action of Urtica dioica in reducing hyperglycemia is illustrated in Fig.
2. There were reports investigated intracellular changes in animals receiving
Urtica dioica. Two studies showed that hydroalcoholic extract of Urtca
Dioica reduces density of astrocytes in dentate gyrus in the diabetic rats (Jahanshahi
et al., 2009; Fazeli et al., 2008
). Another study demonstrated that this extract has no significant neuroprotective
benefit in diabetes-induced loss of pyramidal cells in the CA3 hippocampal subfields
of young diabetic rats (Fazeli et al., 2010).
||Human and animal studies considering antidiabetic effect of
|STZ: Streptozotocin, i.v: Intravenous, i.p: Intraperitoneal,
NOD: Non-obese diabetic
|| Suggested mechanisms of action of Urtica dioica in
Three studies pointed the effect of Urtica dioica on renal complications
of diabetes. In another study, the protective effect of Urtica dioica
on morphometric and histological alterations in streptozotocin diabetic rats
were reported (Golalipour et al., 2009a). Another
study showed that Urtica dioica has no protection on renal complication
of diabetes and even causes nephrotoxicity (Gunes et
al., 1999). Another research revealed that Urtica has no effect on morphometric
indices in diabetic rats (Golalipour et al., 2007a).
One study noticed that Urtica dioica can modulate the main morphometric
indices of liver such as area of hepatocytes, nuclei and nucleolus in periportal
and perivenous zones (Golalipour et al., 2009b).
Another study showed that Urtica dioica has antioxidant effect in diabetes
which influences lipid peroxidation and antioxidative activity of glutathione
S-transferases in the liver of diabetic NOD mice (Petlevski
et al., 2003). Scientists in 2007 showed protective activity of Urtica
dioica in beta-cells of Langerhans in hyperglycemic rats (Golalipour
and Khouri, 2007b).
Looking back demonstrates that natural remedies have played an important role
in people's daily life in most parts of the world. Some herbs are traditionally
used in treatment of type 2 diabetes. Urtica dioica has been used traditionally
in Morocco, Turkey, Brazil, Jordan, Iran and many other countries. The present
study reviewed the effects of Urtica dioica on diabetes. Most of the
included studies concluded that Urtica dioica can significantly reduce
blood sugar. Researchers have proposed several mechanisms for this process.
Possible effects of Urtica dioica could be categorized into two groups
of pancreatic and extrapancreatic. Regarding to pancreatic effects, they have
been suggested that Urtica dioica enhances the secretagogue function
of islets of Langerhance and it is a potent stimulator of insulin release from
β-cells (Bijan et al., 2003). Urtica has
shown protective effect on β-cells in hyperglycemic rats (Fazeli
et al., 2008).
Extra-pancreatic mechanisms that Urtica dioica affects glucose homeostasis
include inhibition of intestinal absorption of glucose (Bnouham
et al., 2003), inhibitory effects on the alpha amylase activity in
a dose dependent-manner (Nickavar and Yousefian, 2010)
and forming unique glucose permeable pores to facilitate glucose uptake (Domola
et al., 2010).
On the other hand, investigators found that Urtica dioica has benefits
on complications of diabetes and can cause a delay in development of late complications
associated with hyperglycemia. They showed that Urtica can compensate granul
cells in dentate gyrus after diabetes-induced cell loss, so it can ameliorate
cognitive impairment in diabetes (Jahanshahi et al.,
2009; Fazeli et al., 2008). A further effect
of Urtica dioica is in the liver. Urtica has shown antioxidant effect
in the liver, which can influence lipid peroxidation and increase the antioxidative
activity of glutathione S-transferases in the liver (Petlevski
et al., 2003) and can cause a little modulation in the main morphometric
indices of live (Golalipour et al., 2009b). Meanwhile,
platelet hyperaggregability is one of the pathogenesis of diabetes which Urtica
can reduce and thus prevents cardiovascular complications of diabetes (El-Haouari
et al., 2007). Its effects on kidney have been controversial. Among
studies conducted in this field, only one showed protective effects of Urtica
dioica on renal morphometric and histological alterations of diabetes (Golalipour
et al., 2009a).
Besides in some in vivo and in vitro studies, Urtica dioica had no effects
on diabetes or vice versa showed toxic effects on kidney and liver (Ramos
et al., 1992; Swanston-Flatt et al., 1989;
Gunes et al., 1999). And its mechanism of action
is still controversial (Mobaseri et al., 2010).
In conclusion, considering all available evidences, the integration of chemical
drugs with Urtica dioica may be possible and recommendable for management
of diabetes. As a matter of fact, antioxidant composition of Urtica dioica
should be noted as an excellent influencing element in management of diabetes
and its complications (Rahimi et al., 2005; Momtaz
and Abdollahi, 2010; Sarkhail et al., 2007;
Mohseni-Salehi-Monfared et al., 2009; Milani
et al., 2005; Malihi et al., 2009).
In the recent years, Urtica dioica in combination with Rosa canina, Tanacetum
vulgare and selenium and electromagnetic processing (named and patented as IMOD)
has been tested in rat diabetes 1 model and found to improve oxidative and immunological
distresses of type-1 immunogenic diabetes but could not normalize blood glucose
(Mohseni-Salehi-Monfared et al., 2010). Of course
evidence-based supports on the efficacy and safety of Urtica in diabetes are
too few and needs further well-designed clinical trials. IMOD containing Urtica
dioica is a good example of this hypothesis that has been found useful in
experimental colitis (Baghaei et al., 2010),
in human sever sepsis (Mahmoodpoor et al., 2010)
and as an immunomodulator (Khairandish et al., 2009).
Meanwhile better experimental studies should be conducted to elucidate exact mechanism of action of Urtica dioica in diabetes.
This study is the outcome of an in-house non-financially supported study.
Sicree, R., J. Shaw and P. Zimmet, 2007.
Diabetes and Impaired Glucose Tolerance: Delice Gan Diabetes Atlas. 3rd Edn., International Diabetes Federation, Brussels, Belgium
Shaw, J.E., R.A. Sicree and P.Z. Zimmet, 2010.
Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract., 87: 4-14.CrossRef | PubMed | Direct Link |
Hasani-Ranjbar, S., B. Larijani and M. Abdollahi, 2009.
A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm. Allergy Drug Targets, 8: 2-10.CrossRef | PubMed | Direct Link |
Hasani-Ranjbar, S., B. Larijani and M. Abdollahi, 2008.
A systematic review of Iranian medicinal plants useful in diabetes mellitus. Arch. Med. Sci., 4, 3: 285-292.
Ramos, R.R., F. Alarcon-Aguilar, A. Lara-Lemus and J.L. Flores-Saenz, 1992.
Hypoglycemic effect of plants used in Mexico as antidiabetics. Arch. Med. Res., 23: 59-64.PubMed |
Swanston-Flatt, S.K., C. Day, P.R. Flatt, B.J. Gould and C.Y. Bailey, 1989.
Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res., 10: 69-73.PubMed |
Hirano, T., M. Homma and K. Oka, 1994.
Effects of stinging nettle root extracts and their steroidal components on the Na+
-ATPase of the benign prostatic hyperplasia. Planta Medica, 60: 30-33.CrossRef | PubMed | Direct Link |
Krzeski, T., M. Kazon, A. Bordowski, A. Witeska and J. Kuczera, 1993.
Combined extracts of Urtica dioica
and Pygeum africanum
in treatment of benign prostatic hyperplasia: Double-blind comparison of two doses. Clin. Ther., 15: 1011-1020.PubMed |
Kayser, K., J. Bubenzer, G. Kayser, S. Eichhorn and N.V. Bovin et al
Expression of lectim, interleakin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis. Anal. Quant. Cytol. Histol., 17: 135-142.PubMed |
Obertreis, B., K. Giller, T. Teucher, B. Behnke and H. Schmitz, 1996.
Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid. Arzneimittelforschung, 46: 52-56.Direct Link |
Mittman, P., 1990.
Randomized double blind study of freeze dried Urtica dioica
in the treatment of allergic rhinitis. Planta Med., 56: 44-47.CrossRef | PubMed |
Said, O., S. Fulder, K. Khali, H. Azaizeh, E. Kassis and B. Saad, 2008.
Maintaining a physiological blood glucose level with 'glucolevel', a combination of four anti-diabetes plants used in traditional Arab herbal medicine. Evidence-Based Complementary Alternative Med., 5: 421-428.CrossRef | Direct Link |
Bnouham, M., F.Z. Merhfour, A. Zyyat, M. Aziz, A. Legssyer and H. Mekhfi, 2010.
Anti-diabetic effect some medicinal plants of Oriental morocco in neonatal non-insulin-dependent diabetes mellitus rats. Hum. Exp. Toxicol.CrossRef |
Bnouham, M., F.Z. Merhfour, A. Ziyat, H. Mekhfi, M. Aziz and A. Legssyer, 2003.
Antihyperglycemic activity of the aqueous extract of Urtica dioica
. Fitoterpia, 74: 677-681.Direct Link |
Farzami, B., D. Ahmadvand, S. Vardasbi, F.J. Majin and S. Khaghani, 2003.
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., 89: 47-53.CrossRef | PubMed | Direct Link |
Petlevski, R., M. Hadzija, M. Slijepcevic and D. Juretic, 2001.
Effect of antidiabetes herbal preparation on serum glucose and fructosamine in NOD mice. J. Ethnopharmacol., 75: 181-184.Direct Link |
Shahraki, M.R., H. Mirshekari, A.R. Shahraki, E. Shahraki and K.H. Divband, 2008.
Effect of Urtica dioica
boiling on serum glucose, insulin and lipids in fructose-fed male rats. J. Ofogh-e-Danesh Gonabad Univ. Med. Sci. Health Services, 14: 10-15.Direct Link |
Fathi-Azad, F., A. Garjani, N. Maleki and S. Ranjdost, 2005.
Study of the hypoglycemic activity of the hydroalcoholic extract of Urtica dioica
in normal and diabetic rat. Pharm. Sci., 2: 65-69.Direct Link |
Khouri. V. and M.J. Golalipour, 2006.
Chronic effect of the hydroalcoholic extract of Urtica dioica
leaves in regeneration of β-cells of hyperglycemic STZ rats. J. Med. Plants, 5: 23-30.
Golalipour, M.J., M.A. Gharravi, S. Ghafari and A. Azarhoush, 2009.
Protective effect of urtica dioicaon renal morphometric and histologic alterations in streptozotocin diabetic rats. J. Babol Univ. Med. Sci., 10: 14-22.
Golalipour, M.J., S. Ghafari, V. Kouri and A.A. Kestkar, 2010.
Proliferation of the β-cells of pancreas in diabetic rats treated with Urtica dioica
. Int. J. Morphol., 28: 399-404.Direct Link |
Gunes, H.V., I. Degirmenci, M. Aydin, B. Bozan and E. Aral et al
The effects of Rumex patientia
L. and Urtica dioica
L. on some blood and urine parameters and liver and kidney histology in diabetic rats. Turk. J. Med. Sci., 29: 227-232.Direct Link |
Neef, H., P. Declercq and G. Laekeman, 1995.
Hypoglycemic activity of selected European plants. Phytother. Res., 9: 45-48.CrossRef |
Jahanshahi, M., M.J. Golalipour and M. Afshar, 2009.
The effect of Urtica dioica
extract on the number of astrocytes in the dentate gyrus of diabetic rats. Folia Morphol., 68: 93-97.PubMed |
Fazeli, S.A., A.M. Gharravi, S. Ghafari, M. Jahanshahi and M.J. Golalipour, 2008.
The granul density of the dentate gyrus following administration of Urtica dioica
extract on young diabetic rats. Folia Morphol., 67: 196-204.PubMed |
Fazeli, S.A., A.M. Gharravi, S. Ghafari, M. Jahanshahi and M.J. Golalipour, 2010.
Effects of Urtica dioica
extract on CA3 hippocampal pyramidal cell loss in young diabetic rats. Neural Regeneration Res., 5: 901-905.
Golalipour, M.J., A.M. Gharravi, S. Ghafari and M. Afshar, 2007.
Effect of Urtica dioica
on morphometric indices of kidney in streptozotocin diabetic rats-a stereological study. Pak. J. Biol. Sci., 10: 3875-3879.CrossRef | PubMed | Direct Link |
Golalipour, M.J. and V. Khouri, 2007.
The protective activity of Urtica dioica
leaves on blood glucose concentration and beta-cells in streptozocin-diabetic rats. Pak. J. Biol. Sci., 10: 1200-1204.PubMed |
Petlevski, R., M. Hadzija, M. Slijepcevic, D. Juretic and J. Petrik, 2003.
Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytother. Res., 17: 311-314.Direct Link |
Golalipour, M.J., S. Ghafari and M.H. Farsi, 2009.
Effect of Urtica dioica
L. extract on quantitative morphometric alterations of liver parenchymal cells in STZ diabetic rats. Int. J. Morphol., 27: 1339-1344.Direct Link |
Nickavar, B. and N. Yousefian, 2010.
Evaluation of α-amylase inhibitory activities of selected antidiabetic medicinal plants. J. fur Verbraucherschutz und Lebensmittelsicherheit.CrossRef |
Domola, M.S., V. Vu, C.A. Robson-Doucette, G. Sweeney and M.B. Wheeler, 2010.
Insulin mimetics in Urtica dioica
: Structural and computational analyses of Urtica dioica
extracts. Phytother. Res., 24: S175-S182.CrossRef |
El-Haouari, M., I. Jardin, H. Mekhfi, J.A. Rosado and G.H. Salido, 2007.
Urtica dioica extract reduces platelet hyperaggregability in type 2 diabetes mellitus by inhibition of oxidant production, Ca2+ mobilization and protein tyrosine phosphorylation. J. Applied Biomed., 5: 105-113.
Mobasseri, M., A. Bahrami, N. Zargami, A. Aliasgarzadeh and M. Rhmati et al
Effect of total extract of Urtica dioica
on insulin and C-peptide secretion from rat (RIN5F) pancreatic β cells and glucose utilization by human muscle cells. Iran. J. Endocrinol. Metab., 11: 721-727.Direct Link |
Rahimi, R., S. Nikfar, B. Larijani and M. Abdollahi, 2005.
A review on the role of antioxidants in the management of diabetes and its complications. Biomed. Pharmacother., 59: 365-373.PubMed | Direct Link |
Momtaz, S. and M. Abdollahi, 2010.
An update on pharmacology of Satureja
species; From antioxidant, antimicrobial, antidiabetes and anti-hyperlipidemic to reproductive stimulation. Int. J. Pharmacol., 6: 346-353.CrossRef | Direct Link |
Sarkhail, P., S. Rahmanipour, S. Fadyevatan, A. Mohammadirad and G. Dehghan et al
Antidiabetic effect of Phlomis anisodonta
: Effects on hepatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Pharmacol. Res., 56: 261-266.CrossRef | Direct Link |
Monfared, S.S.M.S., B. Larijani and M. Abdollahi, 2009.
Islet transplantation and antioxidant management: A systematic review. World J. Gastroenterol., 15: 1153-1161.CrossRef | PubMed | Direct Link |
Malihi, F., A. Hosseini-Tabatabaei, H. Esmaily, R. Khorasani, M. Baeeri and M. Abdollahi, 2009.
Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus. Cent. Eur. J. Biol., 4: 369-380.CrossRef |
Mohseni-Salehi-Monfared, S.S., E. Habibollahzadeh, H. Sadeghi, M. Baeeri and M. Abdollahi, 2010.
Efficacy of Setarud (IMODTM
), a novel electromagnetically-treated multi-herbal compound, in mouse immunogenic type-1 diabetes. Arch. Med. Sci., 6: 663-669.CrossRef |
Baghaei, A., H. Esmaily, A.H. Abdolghaffari, M. Baeeri, F. Gharibdoost and M. Abdollahi, 2010.
Efficacy of Setarud (IMOD®
), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab. Indian J. Biochem. Biophys., 47: 219-226.PubMed | Direct Link |
Mahmoodpoor, A., M. Mojtahedzadeh, A. Najafi, A. Ahmadi and A. Dehnadi-Moghadam et al
Examination of setarud (IMODTM
) in the management of patients with severe sepsis. DARU-J. Pharm. Sci, 18: 23-28.Direct Link |
Khairandish, P., M. Mohraz, B. Farzamfar, M. Abdollahi and M.H. Shahhosseiny et al
Preclinical and phase 1 clinical safety of Setarud (IMODTM
), a novel immunomodulator. DARU, 17: 148-156.Direct Link |
Milani, E., S. Nikfar, R. Khorasani, M.J. Zamani and M. Abdollahi, 2005.
Reduction of diabetes‐induced oxidative stress by phosphodiesterase inhibitors in rats. Comparative Biochem. Physiol. Part C Toxicol. Pharmacol., 140: 251-255.CrossRef | Direct Link |