Hematoprotective and Nephroprotective Effects of Achillea millefolium Aqueous Extract in Diabetic Mice

Document Type: Original paper


1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.

2 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.


Background and objectives: Achillea millefolium has been used in medicine as an anti-fungal, antibacterial and antioxidant agent. The present study was carried out to assess the hematoprotective and nephroprotective activities of Achillea millefolium aqueous extract (AMAE) in diabetic mice. Methods:  Seventy mice were used anddiabetes was experimentally induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in 60 mice. The mice with serum glucose level>250 mg/dL were considered diabetic. After three days, they were divided randomly into 7 groups. Group 1 and 2 were non-diabetic and untreated diabetic controls, respectively. Group 3 received 30 mg/kg glibenclamide orally. Groups 4, 5, 6 and 7 were given 10, 30, 90 and 270 mg/kg of AMAE, respectively for 20 days orally. At 20th day, the mice were dissected, and the blood and kidney samples were collected for hematological and pathological parameters analysis. Results:  Daily treatment of diabetic mice with 10, 30, 90 and 270 mg/kg doses of AMAE at all doses especially 90 and 270 mg/kg significantly declined blood glucose, creatinine and urea levels and improved RBC (Red blood cell), platelet and WBC (White blood cell) parameters, compared to the untreated diabetic control. Also kidney of the treated diabetic mice with AMAE at all doses especially 270 mg/kg indicated significant improvement of the renal tissue compared to the untreated diabetic mice. Conclusion: The present research demonstrated the hypoglycemic properties of AMAE, offering to be suggested as an anti-diabetic supplement.


[1] Ripsin CM, Kang H, Urban RJ. Management of blood glucose in type 2 diabetes mellitus. Am Fam Physician. 2009; 79(1): 29-36.

[2] Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009; 32(7): 1335-1343.

[3] Le-Devehat C, Khodabandehlou T, Vimeux M. Impaired hemorheological properties in diabetic patients with lower limb arterial ischaemia. Clin Hemorheol Microcirc. 2001; 25(2): 43-48.

[4] Demirtas L, Degirmenci H, Akbas EM, Ozcicek A, Timuroglu A, Gurel A, Ozcicek F. Association of hematological indicies with diabetes, impaired glucose regulation and microvascular complications of diabetes. Int J Clin Exp Med. 2015; 8(7): 11420–11427.

[5] Mogensen CE, Anderson MJF. Increased kidney size and glomerular filtration rate in untreated juvenile diabetes: normalization by insulin-treatment. Diabetologia. 1975; 11(3): 221-224.

[6] Christiansen JS, Gammelgaard J, Tronier B, Svendsen PA, Parving HH. Kidney function and size in diabetes before and during initial insulin treatment. Kidney Int. 1982; 21(5): 683-688.

[7] Najafi F, Goodarzi N, Zangeneh MM, Zangeneh A, Hagh-Nazari L. Antidiabtic and hepatoprotective effects of bitter fraction of Stevia rebaudiana alcoholic extract on streptozotocin-induced diabetic male mice. J Rafsanjan Univ Med Sci.2017; 16(6): 493-504.

[8] Shojaii A, Hashem-Dabaghian F, Goushegir A, Abdollahi-Fard M. Antidiabetic plants of Iran. Acta Medica Iranica. 2011; 49(10): 637-642.

[9] Hagh-Nazari L, Goodarzi N, Zangeneh MM, Zamgeneh A, Tahvilin R, Moradi R. Stereological study of kidney in streptozotocin-induced diabetic mice treated with ethanolic extract of Stevia rebaudiana (bitter fraction). Comp Clin Pathol. 2017; 26(2): 455-463.

[10] Bahrami E, Khedri MR, Zangeneh MM, Abiari M, Zangeneh A, Amiri-Paryan A, Tahvilian R, Moradi R. Effect of Anethum graveolens aqueous extract on blood fasting glucose and hematological parameters in diabetic male BALB/c mice. Onl J Vet Res. 2017; 21(12): 784-793.

[11] Foroughi A, Zangeneh MM, Kazemi N, Zangeneh A. An in vitro study on antimicrobial properties of Allium noeanum Reut Ex Regel: an ethnomedicinal plant. Iran J Publ Health. 2016; 45(2): 32.

[12] Sherkatolabbasieh H, Hagh-Nazari L, Shafiezadeh S, Goodarzi N, Zangeneh MM, Zangeneh A. Ameliorative effects of the ethanolic extract of Allium saralicum R.M. Fritsch on CCl4-induced nephrotoxicity in mice: a stereological examination. Arch Biol Sci. 2017; 69(3): 535-543.

[13] Zangeneh MM, Najafi F, Tahvilian R, Salmani S, Haghnazari L, Zangeneh A, Moradi R. Ethnomedicinal plants: in vitro antibacterial effects of ethanolic extract of Stevia rebaudiana. Int J Ayu Pharm Chem. 2017; 6(1): 251-259.

[14] Faramarzi E, Goorani S, Zangeneh MM, Zangeneh A, Amiri-Paryan A, Almasi M, Najafi F, Tahvilian R. Effect of Punica granatum on wound healing in male Sprague Dawley rats. Onl J Vet Res. 2017; 21(9): 543-548.

[15] Moradi R, Hajialiani M, Zangeneh MM, Zangeneh A, Tahvilian R, Hidaryan H, Rezaeeas N, Kohneshin A. Antibacterial properties of an Iranian ethnomedicinal plant. Int J Ayu Pharm Chem. 2017; 6(3): 128-137.

[16] Zangeneh MM, Goodarzi N, Zangeneh A, Najafi F, Tahvilian R. Hypoglycemic, nephroprotective effects of aqueous extract of Stevia rebaudiana (sweet fraction) in streptozotocin-induced diabetic mice. J Ardabil Univ Med Sci. 2018; 17(4): 437-446.

[17] Zangeneh MM, Goodarzi N, Zangeneh A, Tahvilian R, Najafi F. Amelioration of renal structural changes in STZ-induced diabetic mice with ethanolic extract of Allium saralicum R.M. Fritsch. Comp Clin Pathol. In press.

[18] Akram M. Minireview on Achillea millefolium Linn. J Membr Biol. 2013; 246(9): 661-663.

[19] Benedek B, Kopp B. Achillea millefolium L. revisited: recent findings confirm the traditional use. Wien Med Wochenschr. 2007; 157(13-14): 312-314.

[20] Dalsenter P, Cavalcanti A, Andrade A, Araújo S, Marques M. Reproductive evaluation of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar rats. Reprod Toxicol. 2004; 18(6): 819-823.

[21] Benedek B, Rothwangl-Wiltschnigg K, Rozema E, Gjoncaj N, Reznicek G, Jurenitsch J, Kopp B, Glasl S. Yarrow (Achillea millefolium L. s.l.): pharmaceutical quality of commercial samples. Pharmazie. 2008; 63(1): 23-26.

[22] Lakshmi T, Geetha RV, Anitha R, Aravind KS. Yarrow (Achillae millefolium Linn.) An herbal medicinal plant with broad therapeutic use- a review. Int J Pharm Sci Rev Res. 2011; 9(2): 136-141.

[23] Zolghadri Y, Fazeli M, Kooshki M, Shomali T, Karimaghayee N, Dehghani M. Achillea millefolium L. hydro-alcoholic extract protects pancreatic cells by down regulating IL- 1β and iNOS gene expression in diabetic rats. Int J Mol Cell Med. 2014; 4(4): 255-262.

[24] Ahmed D, Kumar V, Verma A, Gupta PS, Kumar H, Dhingra V, Mishra V, Sharma M. Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/ dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats. Complement Altern Med. 2014; 14(2): 243-260.  

[25] Schiekofer S, Andrassy M, Chen J, Rudofsky G, Schneider J, Wendt T, Stefan N, Humpert P, Fritsche A, Stumvoll M, Schleicher E, Häring HU, Nawroth PP, Bierhaus A. Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes. 2003; 52(3): 621-633.

[26] Weiss RB. Streptozocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treat Rep. 1982; 66(3): 427-438.

[27] Karunanayake EH, Baker JR, Christian RA, Hearse DJ, Mellows G. Autoradiographic study of the distribution and cellular uptake of (14C) - streptozotocin in the rat. Diabetologia. 1976; 12(2): 123-128.

[28] Haluzik M, Nedvidkova J. The role of nitric oxide in the development of streptozotocin-induced diabetes mellitus: experimental and clinical implications. Physiol Res. 2000; 49(S1): 37-42.

[29] Chávez-Silva F, Cerón-Romero L, Arias-Durán L, Navarrete-Vázquez G, Almanza-Pérez J, Román-Ramos R, Ramírez-Ávila G, Perea-Arango I, Villalobos-Molina R, Estrada-Soto S. Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities. J Ethnopharmacol. 2018; 15(1): 1-7.

[30] Mansi K, Lehham J. Effects of Artemisia sieberi Bessa a herba-alba on heart rate and some hematological values in normal and alloxan-induced diabetic rats. J Basic Appl Sci. 2008; 4(1): 57-72.

[31] Kotharia R, Bokariya P. A comparative study of haematological parameters in type 1 diabetes mellitus patients and healthy young adolescents. Int J Biol Med Res. 2012; 3(4): 2429-2432.

[32] Oyedemi SO, Adewusi EA, Aiyegoro OA, Akinpeanolu DA. Antidiabetic and hematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozocin-induced diabetic wister rats. Asian Pac J Trop Biomed. 2011; 1(5): 353-358.

[33] Arun GS, Ramesh KG. Improvement of insulin sensitivity by perindopril in spontaneously hypertensive and streptozotocin diabetic rats. Indian J Pharmacol. 2002; 34(3): 156-164.

[34] Akomas SC, Okafor AI, Ijioma SN. Glucose level, haematological parameters and lipid profile in Ficus sur treated diabetic rats. Compr J Agric Biol Sci. 2014; 2(1): 5-11.

[35] Verma N, Amresh G, Sahu PK, Mishra N, Singh AP, Rao CV. Antihyperglycemic activity, antihyperlipidemic activity, hematological effects and histopathological analysis of Sapinus mukorossi Ganertan fruits in streptozocin induced diabetic rats. Asian Pac J Trop Dis. 2012; 5(7): 518-522.

[36] Abu-Zaiton AS. Antidiabetic activity of Ferula asafoetida extract in normal and alloxan induced diabetic rats. Pak J Biol Sci. 2010; 13(2): 97-100.

[37] Uko EK, Erhabor O, Isaac IZ, Abdulrahaman Y, Adias TC, Sani Y, Shehu RS, Liman HM, Dalltu M, Mainastra AS. Some haematological parameters in patients with type 1 diabetes in Sokoto, north western Nigeria. J Blood Lymph. 2013; 3(1): 2165-7831.

[38] Willams WJ, Bentler E, Erslev AJ, Lictman MA. Thrombocytosis. In: Heamatology. 3rd ed. New York:  McGraw-Hill, 1983.

[39] Edet AE, Patrick EB, Olarufemi EA. Haematological parameters of alloxan-induced diabetic rats treated with ethanol extracts and fractions of Nauclea latifolia leaf. Eur Sci J. 2013; 9(27): 203-210.

[40] Ngogang JY. Haematinic activity of Hibiscus cannabinus. Afr J Biotechnol. 2005; 4(8): 833-837.

[41] Mohammed RK, Ibrahim S, Atawodi SE, Eze ED, Suleiman JB, Malgwi IS. Anti-diabetic and haematological effects of n-butanol fraction of Alchornea cordifolia leaf extract in streptozotocin-induced diabetic wistar rats. Sci J Biol Sci. 2013; 2(3): 45-53.

[42] Mahmoud AM, Ahmed OM, Ashour MB, Abdel-Moneim A. Upregulation of PPARγ mediates the antidiabetic effects of flavonoids in high fat diet fed-streptozocin induced type 2 diabetic rats. Int J Bioassays. 2013; 2(5): 756-761.

[43] Halliwell B, Gutteridge J. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J. 1984; 219(1): 1-14.

[44] Masuda Y. Learning toxicology from carbon tetrachloride-induced hepatotoxicity. Yakugaku  Zasshi. 2006; 126(10): 885-899.

[45] Rood AS, McGavran PD, Aanenson JW, Till JE. Stochastic estimates of exposure and cancer risk from carbon tetrachloride released to the air from the rocky flats plant. Risk Anal. 2001; 21(4): 675-695.

[46] Slater TF. Free radical mechanisms in tissue injury. Biochem J. 1984; 222(1): 1-15.