Effects of ethanolic extract of Ferula gummosa oleo-resin in a rat model of streptozotocin-induced diabetes

Mohammad Jalili-Nik , Mohammad Soukhtanloo, Sajad Javanshir, Amirali Jahani Yazdi, Mahdi Esmaeilizadeh, Amir Hossein Jafarian, Ahmad Ghorbani


Previous studies have shown that some plants in the genus of Ferula (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of Ferula gummosa oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL vs 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. Ferula gummosa oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.


Diabetes; Ferula gummosa; Glucose; Lipid; Sesquiterpene coumarins.

Full Text:



Gregg EW, Li Y, Wang J, Rios Burrows N, Ali MK, Rolka D, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370(16):1514-1523.

Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731-b4739.

Domingueti CP, Dusse LM, Carvalho Md, de Sousa LP, Gomes KB, Fernandes AP. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications. 2016;30(4):738-745.

Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Biomed Pharmacother. 2017;96:305-312.

Ghorbani A. Best herbs for managing diabetes: a review of clinical studies. Braz J Pharm Sci. 2013;49(3):413-422.

Hosseini A, Shafiee-Nick R, Ghorbani A. Pancreatic beta cell protection/regeneration with phytotherapy. Braz J Pharm Sci. 2015;51(1):1-16.

Azizian H, Rezvani ME, Esmaeilidehaj M, Bagheri SM. Anti-obesity, fat lowering and liver steatosis protective effects of Ferula asafoetida gum in type 2 diabetic rats: possible involvement of leptin. IJDO. 2012;4(3):120-126.

Raafat K, El-Lakany A. Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain. BMC Complement Altern Med. 2015;15(1):257-270.

Amiri MS, Joharchi MR. Ethnobotanical knowledge of Apiaceae family in Iran: A review. Avicenna J Phytomed. 2016;6(6):621-635.

Moosavi SJ, Habibian M, Peeri M, Azarbayjani MA, Nabavi SM, Nabavi SF, et al. Protective effect of Ferula gummosa hydroalcoholic extract against nitric oxide deficiency-induced oxidative stress and inflammation in rats renal tissues. Clin Exp Hypertens. 2015;37(2):136-141.

Mahboubi M. Ferula gummosa, a traditional medicine with novel applications. J Diet Suppl. 2016;13(6):700-718.

Dadkhah A, Khalaj GR, Fatemi F, Dini S, Hesaraki S, Naij S, et al. Evaluation the role of Ferula gummosa essential oil against the hepatoxicity induced by acetaminophen in animal model. Journal of Medicinal Plants. 2016;4(60):14-23.

Nazari ZE, Iranshahi M. Biologically active sesquiterpene coumarins from Ferula species. Phytother Res. 2011;25(3):315-323.

Xing Y, Li N, Zhou D, Chen G, Jiao K, Wang W, et al. Sesquiterpene coumarins from Ferula sinkiangensis act as neuroinflammation inhibitors. Planta Med. 2017;83(1-02):135-142.

Sayed AA. Ferulsinaic acid attenuation of diabetic nephropathy. Eur J Clin Invest. 2013;43(1):56-63.

Sayed AAR. Ferulsinaic acid modulates SOD, GSH, and antioxidant enzymes in diabetic kidney. Evid Based Complement Alternat Med. 2012;2012.Article ID:580104.

Sayed AA. Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan of Caenorhabditis elegans. J Pharm Pharmacol. 2011;63(3):423-428.

Jalali HT, Ebrahimian ZJ, Evtuguin DV, Neto CP. Chemical composition of oleo-gum-resin from Ferula gummosa. Ind Crops Prod. 2011;33(2): 549-553.

Ghorbani A, Omrani GR, Hadjzadeh MA, Varedi M. Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through phosphodiestrase-3B enzyme. Horm Metab Res. 2013;45(3):221-225.

Ghorbani A, Mohebbati R, Jafarian AH, Vahedi MM, Hosseini SM, Soukhtanloo M, et al. Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root. Regul Toxicol Pharmacol. 2016;77:35-41.

Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659-661.

Madesh M, Balasubramanian KA. Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys. 1998;35(3):184-188.

Merzouk H, Madani S, Sari DC, Prost J, Bouchenak M, Belleville J. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes. Clin Sci. 2000;98(1):21-30.

Rath D, Kar DM, Panigrahi SK, Maharana L. Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats. J Ethnopharmacol. 2016;192:442-449.

Lucidi P, Porcellati F, Andreoli AM, Carriero I, Candeloro P, Cioli P, et al. Pharmacokinetics and pharmacodynamics of NPH insulin in type 1 diabetes: the importance of appropriate resuspension before subcutaneous injection. Diabetes Care. 2015;38(12):2204-2210.

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615-1625.

Malenica M, Prnjavorac B, Causevic A, Dujic T, Bego T, Semiz S. Use of databases for early recognition of risk of diabetic complication by analysis of liver enzymes in type 2 diabetes mellitus. Acta Inform Med. 2016;24(2):90-93.

Ogunyinka BI, Oyinloye BE, Osunsanmi FO, Opoku AR, Kappo AP. Protective effects of Parkia biglobosa protein isolate on streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Molecules. 2017;22(10):E1654.

Aliciguzel Y, Ozen I, Aslan M, Karayalcin U. Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats. J Lab Clin Med. 2003;142(3):172-177.

Huang WC, Juang SW, Liu IM, Chi TC, Cheng JT. Changes of superoxide dismutase gene expression and activity in the brain of streptozotocin-induced diabetic rats. Neurosci Lett. 1999;275(1):25-28.

Domínguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care. 1998;21(10):1736-1742.

Adachi T, Nakamura M, Yamada H, Futenma A, Kato K, Hirano K. Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases. Clin Chim Acta. 1994;229(1-2):123-131.

Kimura F, Hasegawa G, Obayashi H, Adachi T, Hara H, Ohta M, et al. Serum extracellular superoxide dismutase in patients with type 2 diabetes: relationship to the development of micro-and macrovascular complications. Diabetes Care. 2003;26(4):1246-1250.

Rassouli FB, Matin MM, Iranshahi M, Bahrami AR, Neshati V, Mollazadeh S, et al. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line. Phytomedicine. 2009;16(2-3):181-187.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.