Effect of Artemisia fruit extract on TNF- α and IL-6 levels in streptozotocin-induced diabetic mice


  • Ekhlass N. Ali Department of Biology, College of Science, Mustansiriyah University, Bagdad, Iraq.
  • Emad Mahmoud Eltyeaf Department of Chemical, College of Science, Mustansiriyah University, Bagdad, Iraq.
  • Ashwaq A. Kadhem Department of Biology, College of Science, Mustansiriyah University, Bagdad, Iraq.
  • Jamela Jouda Department of Biology, College of Science, Mustansiriyah University, Bagdad, Iraq.




Artemisia, Tumor Necrosis Factor- alpha, Interleukin-6


Objective: The present study was conducted to investigate the effects of Artemisia extract on some immunological parameters in streptozotocin-induced diabetic mice.

Methods: After preparation of Artemisia extract, many chemical tests were used to identify the type of element and compounds presented in this plant using many chemical techniques. Thirty five streptozocin (STZ) induced diabetes mice were divided in to 5 groups; the first group provided only with water, the other four groups were consumed orally ingested the plant extract in four different concentration (2000, 1000, 500,250) mg/Kg of body weight. Another 10 mice didn’t injected with STZ were divided in to two groups; one consumed Artemisia (Art group), and the second consumed only normal saline (Cont. group). After 14 days of diabetes induction and Artemisia extract treatment, the mice were sacrificed. Blood and tissue (brain, spleen and kidney) were collected. Fasting blood sugar and insulin levels were determine in the serum. Furthermore Tumor Necrosis Factor- alpha (TNF- α) and Interleukin-6 (IL-6) levels were determined in the serum and aliquots of homogenize tissues.

Results: Results declared that the extract of Artemisia fruit contains high levels of active compounds especially antioxidant compounds. IL-6 and TNF-α levels were decreased while insulin and glucose levels were increased in the STZ- induce mice group. Artemisia extract effects differently on glucose and insulin levels depend on its concentration. Interestingly, IL-6 and TNF-α levels increase in serum, brain and spleen of the STZ-induce mice group consumed different concentration of Artemisia but it normalized in the STZ-induce mice group consumed 250 mg/kg Artemisia, as well as insulin and glucose levels for the same group, while there was no difference in kidney.

Conclusion: Artemisia can control diabetes in 1000 and 500mg/Kg through controlling insulin level, and in the other hand, using the plant extract in 250mg/Kg ,acts as immune modulator for anti-inflammatory agents IL-6 and TNF-α.


1. Moore H, Summerbell C, Hooper L, Cruickshank K, Vyas A, Johnstone P, et al. Dietary advice for treatment of type 2 diabetes mellitus in adults. Cochrane Database Syst Rev. [Review]. 2004(2):CD004097.
2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047-53.
3. Organization WH. Fact Sheet No 3122011.
4. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. [Review]. 1999 Dec;26(3-4):259-65.
5. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. [Review]. 2001 Jul 21;358(9277):221-9.
6. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. Jama. [Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004 Apr 28;291(16):1978-86.
7. Kroder G, Bossenmaier B, Kellerer M, Capp E, Stoyanov B, Muhlhofer A, et al. Tumor necrosis factor-alpha- and hyperglycemia-induced insulin resistance. Evidence for different mechanisms and different effects on insulin signaling. J Clin Invest. 1996 Mar 15;97(6):1471-7.
8. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, et al. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes. [Research Support, Non-U.S. Gov't]. 2002 May;51(5):1596-600.
9. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72.
10. Kaptoge S, Di Angelantonio E, Pennells L, Wood AM, White IR, Gao P, et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. [Research Support, Non-U.S. Gov't]. 2012 Oct 4;367(14):1310-20.
11. Zeng C, Shi X, Zhang B, Liu H, Zhang L, Ding W, et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. J Mol Med (Berl). [Research Support, Non-U.S. Gov't]. 2012 Feb;90(2):175-86.
12. Jagannathan-Bogdan M, McDonnell ME, Shin H, Rehman Q, Hasturk H, Apovian CM, et al. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. 2011 Jan 15;186(2):1162-72.
13. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. [Evaluation Studies Research Support, Non-U.S. Gov't]. 2009 Aug;15(8):921-9.
14. Zhang H, Potter BJ, Cao JM, Zhang C. Interferon-gamma induced adipose tissue inflammation is linked to endothelial dysfunction in type 2 diabetic mice. Basic Res Cardiol. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. 2011 Nov;106(6):1135-45.
15. Wazaify M, Afifi FU, El-Khateeb M, Ajlouni K. Complementary and alternative medicine use among Jordanian patients with diabetes. Complement Ther Clin Pract. [Research Support, Non-U.S. Gov't]. 2011 May;17(2):71-5.
16. Lev E, Amar Z. Ethnopharmacological survey of traditional drugs sold in Israel at the end of the 20th century. J Ethnopharmacol. [Historical Article]. 2000 Sep;72(1-2):191-205.
17. Ghasemi DN. Pharmacopia of Iranian plants. 1 ed. Isfahan: Ministry of Health and Medical Education.Deputy of Food and Medicine.; 2002.
18. Woerdenbag HJ, Bos R, Salomons MC, Hendriks H, Pras N, Malingre TM. Volatile constituents of Artemisia annua L. (Asteraceae). Flav and Frag J. 1993;8:131-7.
19. Bhakuni RS, Jain DC, Sharma RP, Kumar S. Secondary metabolites of Artemisia annua and their biological activity. Current Science. 2001;80:35-28.
20. Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. [Research Support, U.S. Gov't, P.H.S.]. 1994 Feb;60(1):54-7.
21. Iqbal S, Younas U, Chan KW, Zia-Ul-Haq M, Ismail M. Chemical composition of Artemisia annua L. leaves and antioxidant potential of extracts as a function of extraction solvents. Molecules. 2012 May 21;17(5):6020-32.
22. Heide L. Artemisinin in traditional tea preparations of Artemisia annua. Trans R Soc Trop Med Hyg. [Comment Letter]. 2006 Aug;100(8):802.
23. Abad MJ, Bedoya LM, Apaza L, Bermejo P. The artemisia L. Genus: a review of bioactive essential oils. Molecules. [Research Support, Non-U.S. Gov't Review]. 2012 Mar 2;17(3):2542-66.
24. Al-Mustafa AH, Al-Thunibat OY. Antioxidant capacity of some Jordanian medicinal plants used traditionally for the treatment of diabetes. Pak J Biol Sci. 2008;1:351-8.
25. Ferreira JF, Luthria DL. Drying affects artemisinin, dihydroartemisinic acid, artemisinic acid, and the antioxidant capacity of Artemisia annua L. leaves. J Agric Food Chem. [Evaluation Studies]. 2010 Feb 10;58(3):1691-8.
26. Jiang L, Liu H, Wang J, Tan F, Zhao K, Wu X, et al. Characterization and comparison of three transgenic Artemisia annuavarieties and wild-type variety in environmental release trial. Journal of Medicinal Plants Research. 2010;4:2719-28.
27. Helal EGE, Abou- Aouf N, Khattab AM, Zoair MA. Anti-diabetic effect of Artemisia annua (Kaysom) in Alloxan-induced diabetic Rats. The Egyptian Journal of Hospital Medicine. 2014;57:422-30.
28. Kotani M, Matsumoto M, Fujita A. Persimmon leaf extract and astragaliminlibitd evelopment of dermatitis and IgE elevation in NC/Nga mice. Jaller Clim Immunol. 2000;106(1):159-66.
29. Obistioiu D, Cristina RT, Schmerold I, Chizzola R, Stolze K, Nichita I, et al. Chemical characterization by GC-MS and in vitro activity against Candida albicans of volatile fractions prepared from Artemisia dracunculus, Artemisia abrotanum, Artemisia absinthium and Artemisia vulgaris. Chem Cent J. 2014 Jan 29;8(1):6.
30. Goda A, Ohgi S, Kinpara K, Shigemori K, Fukuda K, Schneider EB. Changes in serum BDNF levels associated with moderate-intensity exercise in healthy young Japanese men. Springerplus. 2013;2:678.
31. Alabdallat NG. In vitro antisickling activity of Artemisia Herba-Alba asso (CHIH) methanolic extract on sickle cell disease. Asian J Pharm Clin Res 2016;1(suppl 1):109-12.
32. Yao K, Chen H, Liu K, Langfald A, Yang G, Zhang Y, et al. Kaempferol targets RSK2 and MSK1 to suppress UV radiation-induced skin cancer. Cancer Prev Res (Phila). [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. 2014 Sep;7(9):958-67.
33. Duarte J, Jimenez R, O'Valle F, Galisteo M, Perez-Palencia R, Vargas F, et al. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens. 2002 Sep;20(9):1843-54.
34. Andriantsitohaina R. Regulation of vascular tone by plant polyphenols: role of nitric oxide. Gen Physiol Biophys. [Research Support, Non-U.S. Gov't]. 1999 Dec;18 Suppl 1:3-5.
35. Baumann J, von Bruchhausen F, Wurm G. Flavonoids and related compounds as inhibition of arachidonic acid peroxidation. Prostaglandins. [Comparative Study]. 1980 Oct;20(4):627-39.
36. Jeong SH, Kim J, H. M. In vitro anti- inflammatory activity of the Artemisia Montana leaf ethanol extract in macrophage RAW. Food and Agricultural immunology online journal homepage. 2018;http://www.tandfonline.com/loi/cfai20:1-11.
37. Vijeesh V, Usha PN, Manju MK. Phytochemical Analysis and In vitro Antifungal studies of Medicinal plants Elephantopus scaber,Cyclea peltata and Artemisia japonica. InterJPharm PhytoResear. 2017;9(3):319-22.
38. Swamy MK, Akhtar MS, Sinniah UR. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review. Evid Based Complement Alternat Med. [Review]. 2016;2016:3012462.
39. Graham ML, Janecek JL, Kittredge JA, Hering BJ, Schuurman HJ. The streptozotocin-induced diabetic nude mouse model: differences between animals from different sources. Comp Med. [Comparative Study Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't]. 2011 Aug;61(4):356-60.
40. Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. [Research Support, N.I.H., Extramural Review]. 2011 Jul;45(3):131-40.
41. Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol. 2015 Sep 1;70:5 47 1-20.
42. Kantwerk-Funke G, Burkart V, Kolb H. Low dose streptozotocin causes stimulation of the immune system and of anti-islet cytotoxicity in mice. Clin Exp Immunol. 1991 Nov;86(2):266-70.
43. Khan I, Ahed W, Karim N, Ahmed M, Khan M, ariq S, et al. Antidiabetic activity and histopathological analysis of carnosol isolated from Artemisia indica linn in streptozotocin – induced diabetic rats. Springer Nature. 2017;26(2):335-43.
44. Abdallah H, Abdel- Rahman R, Jaleel GA, Abd El-Kader HAM, El-Marasy S, Zaki ER, et al. Pharmaceutical Effects of Ethanol Extract of Artimisia Herba Alba in Streptozotocin –induced Type 1 diabetes Mellitus in Rats. Biochem Pharmacol (Los Angel). 2015;4:196.
45. Chang XW, Qin Y, Jin Z, Xi TF, Yang X, Lu ZH, et al. Interleukin-6 (IL-6) mediated the increased contraction of distal colon in streptozotocin-induced diabetes in rats via IL-6 receptor pathway. Int J Clin Exp Pathol. [Research Support, Non-U.S. Gov't]. 2015;8(5):4514-24.
46. Yagi M, Takabe W, Matssumi S, Shimode A, Maruyama T, Yonei Y. Screening and selection of anti-glycative materials: Kuromoji (Lindera umbellata). Glycative Stress Research 2017;4(4):317-128.
47. Bokaeian M, Nakhaee A, Moodi B, Farhangi A, Akbarzadeh A. Effects of garlic extract treatment in normal and streptozotocin diabetic rats infected with Candida albicans. Indian J Clin Biochem. 2010 Apr;25(2):182-7.
48. Obolskiy D, Pischel I, Feistel B, Glotov N, Heinrich M. Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety. J Agric Food Chem. [Review]. 2011 Nov 9;59(21):11367-84.
49. Lacy P, Stow JL. Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood. [Research Support, Non-U.S. Gov't Review]. 2011 Jul 7;118(1):9-18.
50. Zarasvand MA, Madani M, Modaresi M. The Effect of Hydroalcoholic Extract of Artemisia dracunculus L. (Tarragon) on Candida albicans Infection in Mice. Jundishapur J Nat Pharm Prod. 2016;11(4):e29911.
51. Kin NW, Sanders VM. It takes nerve to tell T and B cells what to do. J Leukoc Biol. [Review]. 2006 Jun;79(6):1093-104.
52. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. [Research Support, Non-U.S. Gov't]. 2006 Feb;9(2):268-75.
53. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000 Dec;52(4):595-638.
54. Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun. [Research Support, N.I.H., Extramural Review]. 2007 Aug;21(6):736-45.




How to Cite

Ali, E. N., Eltyeaf, E. M., Kadhem, A. A., & Jouda, J. (2019). Effect of Artemisia fruit extract on TNF- α and IL-6 levels in streptozotocin-induced diabetic mice. Journal of Contemporary Medical Sciences, 5(1), 51–58. https://doi.org/10.22317/jcms.v5i1.520

Most read articles by the same author(s)