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Review Article

A Systematic Review of Efficacy and Safety of Urtica dioica in the Treatment of Diabetes

International Journal of Pharmacology: Volume 7 (2): 161-170, 2011

Avin Mehri, Shirin Hasani-Ranjbar, Bagher Larijani and Mohammad Abdollahi

Abstract

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.

How to cite this article:

Avin Mehri, Shirin Hasani-Ranjbar, Bagher Larijani and Mohammad Abdollahi, 2011. A Systematic Review of Efficacy and Safety of Urtica dioica in the Treatment of Diabetes. International Journal of Pharmacology, 7: 161-170.

DOI: 10.3923/ijp.2011.161.170

URL: https://scialert.net/abstract/?doi=ijp.2011.161.170

INTRODUCTION

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, 1990).

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.


Fig. 1: 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).

RESULTS

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).

Table 1: Human and animal studies considering antidiabetic effect of Urtica dioica
STZ: Streptozotocin, i.v: Intravenous, i.p: Intraperitoneal, NOD: Non-obese diabetic

Fig. 2: Suggested mechanisms of action of Urtica dioica in reducing hyperglycemia

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).

DISCUSSION

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.

ACKNOWLEDGMENT

This study is the outcome of an in-house non-financially supported study.

References

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.
PubMedDirect Link

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

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. 10.1177/0960327110362704

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.

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.
CrossRefPubMedDirect 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

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. 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

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.
CrossRefPubMedDirect Link

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 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

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., 1999. 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

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.

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.
PubMedDirect Link

Hirano, T., M. Homma and K. Oka, 1994. Effects of stinging nettle root extracts and their steroidal components on the Na+, K+-ATPase of the benign prostatic hyperplasia. Planta Medica, 60: 30-33.
CrossRefPubMedDirect Link

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

Kayser, K., J. Bubenzer, G. Kayser, S. Eichhorn and N.V. Bovin et al., 1995. 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

Khairandish, P., M. Mohraz, B. Farzamfar, M. Abdollahi and M.H. Shahhosseiny et al., 2009. Preclinical and phase 1 clinical safety of Setarud (IMODTM), a novel immunomodulator. DARU, 17: 148-156.
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.

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

Mahmoodpoor, A., M. Mojtahedzadeh, A. Najafi, A. Ahmadi and A. Dehnadi-Moghadam et al., 2010. Examination of setarud (IMODTM) in the management of patients with severe sepsis. DARU-J. Pharm. Sci, 18: 23-28.
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

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.
CrossRefDirect Link

Mittman, P., 1990. Randomized double blind study of freeze dried Urtica dioica in the treatment of allergic rhinitis. Planta Med., 56: 44-47.
CrossRefPubMed

Mobasseri, M., A. Bahrami, N. Zargami, A. Aliasgarzadeh and M. Rhmati et al., 2009. 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

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

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.
CrossRefDirect 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.
CrossRefPubMedDirect Link

Neef, H., P. Declercq and G. Laekeman, 1995. Hypoglycemic activity of selected European plants. Phytother. Res., 9: 45-48.
CrossRef

Nickavar, B. and N. Yousefian, 2010. Evaluation of α-amylase inhibitory activities of selected antidiabetic medicinal plants. J. fur Verbraucherschutz und Lebensmittelsicherheit. 10.1007/s00003-010-0627-6

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

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

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

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.
PubMedDirect Link

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

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

Sarkhail, P., S. Rahmanipour, S. Fadyevatan, A. Mohammadirad and G. Dehghan et al., 2007. Antidiabetic effect of Phlomis anisodonta: Effects on hepatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Pharmacol. Res., 56: 261-266.
CrossRefDirect 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

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.
CrossRefPubMedDirect Link

Sicree, R., J. Shaw and P. Zimmet, 2007. Diabetes and Impaired Glucose Tolerance: Delice Gan Diabetes Atlas. 3rd Edn., International Diabetes Federation, Brussels, Belgium.

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