Urtica dioica (Gazaneh) Distillate Restores Glucose Metabolism in Diabetic Rats

Fahimeh Zamani‑Garmsiri, Masoumeh Akmali, Ali Gohar, Fatemeh Zal, Atefeh Seghatoleslam


Background: Diabetes has become an important health problem in the world. Natural agents, with antidiabetic property, are potential candidates for improving diabetes. Urtica Dioica Distillate (UDD) or Araghe Gazaneh is widely used for the treatment of diabetes as per traditional medicine. Despite the tremendous use of UDD as an antidiabetic compound in folk medicine, the antidiabetic effects of UDD has been neglected by medical scientists. In this study, we aimed to evaluate the effects of UDD on the glucose metabolism in diabetic rats. Methods: A total of 24 male rats were divided equally into four groups, two treatment and two control groups, each containing normal or Streptozotocin (STZ)–induced diabetic rats. During 4 weeks, control and treatment rats received water or UDD, respectively. Fasting blood sugar (FBS), HbA1c, serum creatinine, blood urea nitrogen, and specific activities of hepatic enzymes including glucokinase (GK), hexokinase (HK), glucose‑6‑phosphate dehydrogenase (G6PD), and muscle glucose transporter type 4 (GLUT4) and liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels were measured. Results: FBS and HbA1c increased in diabetic groups. Treatment with UDD significantly lowered FBS and prevented weight loss. Decreased FBS level was associated with higher activity levels of GK and HK in UDD‑treated diabetic rats. G6PD‑specific activity decreased in diabetic control rats compared to nondiabetic ones, but UDD treatment improved it to the normal levels. A significant decrease in the expression level of GLUT4 was observed in diabetic control rats compared to nondiabetic ones, but UDD increased it to the normal levels. Conclusions: These findings suggest that UDD might exert therapeutic effects against diabetes by improving glucose metabolism and can be used as an alternative or complementary medicine for the treatment of diabetic patients.


Diabetes mellitus; diabetic rats; hepatic enzymes; Urtica Dioica distillate

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Rezaeizadeh H, Alizadeh M, Naseri M, Ardakani M. The

traditional Iranian medicine point of view on health and disease.

Iran J Public Health 2009;38:169‑72.

Bodeker G, Ong C‑K. WHO Global Atlas of Traditional,

Complementary and Alternative Medicine. World Health

Organization; 2005.

Coman C, Rugina OD, Socaciu C. Plants and natural compounds

with antidiabetic action. Not Bot Horti Agrobotanici Cluj‑Napoca


Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the

prevalence of diabetes for 2010 and 2030. Diabetes Res Clin

Pract 2010;87:4‑14.

Maroo J, Vasu VT, Aalinkeel R, Gupta S. Glucose lowering

effect of aqueous extract of Enicostemma littorale Blume in

diabetes: A possible mechanism of action. J Ethnopharmacol


Kavalalı G, Tuncel H, Göksel S, Hatemi H. Hypoglycemic

activity of Urtica pilulifera in streptozotocin‑diabetic rats.

J Ethnopharmacol 2003;84:241‑5.

Qujeq D, Tatar M, Feizi F, Parsian H, Faraji AS, 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;2:21‑6.

Burrowes JD, Van Houten G. Herbs and dietary supplement use

in patients with stage 5 chronic kidney disease. Nephrol Nurs J


Rashidi AA, Mirhashemi SM, Taghizadeh M, Sarkhail P. Iranian

medicinal plants for diabetes mellitus: A systematic review. Pak

J Biol Sci 2013;16:401‑11.

Moore F, Akhbarizadeh R, Keshavarzi B, Tavakoli F. Potential

health risk of herbal distillates and decoctions consumption in

Shiraz, Iran. Biol Trace Elem Res 2015;167:326‑37.

Akdağ A, Öztürk E. Distillation methods of essential oils. Selçuk

Üniversitesi Fen Fakültesi Fen Dergisi 2018;45:22‑31.

Fakher S, Seghatoleslam A, Noorafshan A, Karbalay‑Doust S,

Rahmanifard M, Rashidi M. The impact of echium amoenum

distillate, Aragh Gav‑Zaban, on naturally boosting fertility:

Potential ameliorative role in male mice reproductive parameters.

Iran J Med Sci 2019;44:227‑35.

Seghatoleslam A, Mashkour N, Namavari M, Azarmehr B,

Nejabat M. The potential effects of herbal distillates with hot

and cold temperament on cell metabolic activity and growth:

A preliminary in vitro study. J Pharmaceutical Biomedical Sci


Güneş HV, Değirmenci İ, Aydin M, Bozan B, Aral E, Tunalier Z,

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 1999;29:227‑32.

Council NR. Guide for the Care and Use of Laboratory Animals.

National Academies Press; 2010.

Fakher S, JALALI M, Tabei S, Zeraati H, Javadi E, Sadeghi M,

et al. Effect of vitamins A, E, C and omega‑3 fatty acids on lipid

peroxidation in streptozotocin induced diabetic rats. Iran J Public

Health 2007;36:58‑63.

Khalili A, Nekooeian AA, Khosravi MB, Fakher S. Simultaneous

renal hypertension and type 2 diabetes exacerbate vascular

endothelial dysfunction in rats. Int J Exp Pathol 2012;93:210‑7.

Gohari A, Noorafshan A, Akmali M, Zamani‑Garmsiri F,

Seghatoleslam A. Urtica dioica distillate regenerates pancreatic

beta cells in streptozotocin‑induced diabetic rats. Iran J Med Sci


Kahn R, Hicks J, Muller M, Panteghini M, John G, Deeb L,

et al. Consensus statement on the worldwide standardization

of the hemoglobin A1C measurement: The American Diabetes

Association, European Association for the Study of Diabetes,

International Federation of Clinical Chemistry and Laboratory

Medicine, and the International Diabetes Federation. Diabetes

Care 2007;30:2399‑400.

Davidson AL, Arion WJ. Factors underlying significant

underestimations of glucokinase activity in crude liver extracts:

Physiological implications of higher cellular activity. Arch

Biochem Biophys 1987;253:156‑67.

Ferre T, Pujol A, Riu E, Bosch F, Valera A. Correction of

diabetic alterations by glucokinase. Proc Natl Acad Sci U S A


Vesal M, Zal F, Vaseei M. Effects of teucrium polium on oral

glucose tolerance test, regeneration of pancreatic islets and

activity of hepatic glucokinase in diabetic rats. Arch Iran Med


Akmali M, Ahmadi R, Vessal M. Pre‑and post‑treatment of

streptozocin administered rats with melatonin: Effects on

some hepatic enzymes of carbohydrate metabolism. Arch Iran

Med (AIM) 2010;13:105‑10.

Bottomley R, Pitot H, Potter VR, Morris H. Metabolic

adaptations in rat hepatomas: V. Reciprocal relationship between

threonine dehydrase and glucose‑6‑phosphate dehydrogenase.

Cancer Res 1963;23:400‑9.

Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin

in streptozocin‑induced diabetic rats. Comp Biochem Physiol C

Toxicol Pharmacol 2003;135:357‑64.

Bradford MM. A rapid and sensitive method for the quantitation

of microgram quantities of protein utilizing the principle of

protein‑dye binding. Anal Biochem 1976;72:248‑54.

Chen M, Zheng H, Xu M, Zhao L, Zhang Q, Song J, et al.

Changes in hepatic metabolic profile during the evolution of

STZ‑induced diabetic rats via an 1H NMR‑based metabonomic

investigation. Biosci Rep 2019;39BSR20181379. doi: 10.1042/


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.

Bijan F, Ahmadvand D, Vardasbi S, Majin F, Khaghani S.

Induction of insulin secretion by a component of Urica dioica

leave extract in perfused islets of langerhans and its in vivo effects

in normal and streptozotocin diabetic rats. Ethnopharmacology


Fazeli S, Gharravi A, Ghafari S, Jahanshahi M, Golalipour M.

The granule cell density of the dentate gyrus following

administration of Urtica dioica extract to young diabetic rats.

Folia Morphol 2008;67:196‑204.

Bnouham M, Merhfour F‑Z, Ziyyat A, Mekhfi H, Aziz M,

Legssyer A. Antihyperglycemic activity of the aqueous extract of

Urtica dioica. Fitoterapia 2003;74:677‑81.

Nickavar B, Yousefian N. Evaluation of α‑amylase inhibitory

activities of selected antidiabetic medicinal plants. J Verbrauch

Lebensm 2011;6:191‑5.

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

;24(Suppl 2):S175‑82.

Golalipour MJ, Ghafari S, Kouri V, Kestkar AA. Proliferation of

the β‑cells of pancreas in diabetic rats treated with urtica dioica.

Int J Morphol 2010;28:399‑404.

Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D,

Peterson CM, et al. Tests of glycemia in diabetes. Diabetes Care


Matschinsky FM, Wilson DF. The central role of glucokinase in

glucose homeostasis: A perspective 50 years after demonstrating

the presence of the enzyme in islets of Langerhans. Front Physiol

;10:148. doi: 10.3389/fphys.2019.00148.

Díaz‑Flores M, Ibáñez‑Hernández MA, Galván RE, Gutiérrez M,

Durán‑Reyes G, Medina‑Navarro R, et al. Glucose‑6‑phosphate

dehydrogenase activity and NADPH/NADP+ratio in liver and

pancreas are dependent on the severity of hyperglycemia in rat.

Life Sci 2006;78:2601‑7.

Kletzien R, Harris P, Foellmi L. Glucose‑6‑phosphate

dehydrogenase: A” housekeeping” enzyme subject to

tissue‑specific regulation by hormones, nutrients, and oxidant

stress. FASEB J 1994;8:174‑81.

Stumpo DJ, Kletzien RF. Regulation of glucose‐6phosphate dehydrogenase mRNA by insulin and the

glucocorticoids in primary cultures of rat hepatocytes. FEBS

J 1984;144:497‑502.

Golalipour MJ, Khori V. The protective activity of Urtica

dioica leaves on blood glucose concentration and beta‑cells in

streptozotocin‑diabetic rats. Pak J Biol Sci 2007;10:1200‑4.

Vargas E, Podder V, Sepulveda MAC. Physiology, Glucose

Transporter Type 4 (GLUT4). StatPearls: StatPearls Publishing;

Kadan S, Saad B, Sasson Y, Zaid H. In vitro evaluations of

cytotoxicity of eight antidiabetic medicinal plants and their effect

on GLUT4 translocation. Evid Based Complement Alternat Med

;2013:549345. doi: 10.1155/2013/549345.

Davies GF, Khandelwal RL, Wu L, Juurlink BH, Roesler WJ.

Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene

expression by troglitazone: A peroxisome proliferator‑activated

receptor‑γ (PPARγ)‑independent, antioxidant‑related mechanism1.

Biochem Pharmacol 2001;62:1071‑9.