Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

IMPACT FACTOR 2018: 0.504
5-year IMPACT FACTOR: 0.583

CiteScore 2018: 0.63

SCImago Journal Rank (SJR) 2018: 0.266
Source Normalized Impact per Paper (SNIP) 2018: 0.311

ICV 2017: 154.48

Open Access
See all formats and pricing
More options …
Volume 4, Issue 3


Volume 10 (2015)

Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus

Farshad Malihi
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Azadeh Hosseini-Tabatabaei
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • BC Professional Fire Fighters’ Burn and Wound Healing Research Laboratory, Department of Surgery, University of British Columbia, V6H 3Z6, Vancouver, BC, Canada
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hadi Esmaily
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Reza Khorasani
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maryam Baeeri
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mohammad Abdollahi
  • Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), 1417614411, Tehran, Iran
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-07-26 | DOI: https://doi.org/10.2478/s11535-009-0014-4


Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20, 40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human T1DM remains to be elucidated by clinical trials.

Keywords: Silymarin; Diabetes; Antioxidants; Streptozotocin; Oxidative stress; Inflammatory cytokines

  • [1] Bardsley J.K., Want L.L., Overview of diabetes, Crit. Care Nurs. Q., 2004, 27, 106–112 Google Scholar

  • [2] Morran M.P., Omenn G.S., Pietropaolo M., Immunology and genetics of type 1 diabetes, Mt Sinai J. Med., 2008, 75, 314–327 http://dx.doi.org/10.1002/msj.20052Google Scholar

  • [3] Mollah Z.U., Pai S., Moore C., O’sullivan B.J., Harrison M.J., Peng J., et al., Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes, J. Immunol., 2008, 180, 3166–3175 Google Scholar

  • [4] Mohseni-Salehi-Monfared S.S., Larijani B., Abdollahi M., Islet transplantation and antioxidant management: A systematic review, World J. Gastroenterol., 2009, 15, 513–520 http://dx.doi.org/10.3748/wjg.15.1153CrossrefGoogle Scholar

  • [5] Kajbaf F., Mojtahedzadeh M., Abdollahi M., Mechanisms underlying stress-induced hyperglycemia in critically ill patients, Therapy, 2007, 4, 97–106 http://dx.doi.org/10.2217/14750708.4.1.97CrossrefGoogle Scholar

  • [6] Gille L., Schott-Ohly P., Friesen N., Schulte im Walde S., Udilova N., Nowl H., et al., Generation of hydroxyl radicals mediated by streptozotocin in pancreatic islets of mice in vitro, Pharmacol. Toxicol., 2002, 90, 317–326 CrossrefGoogle Scholar

  • [7] Kawasaki E., Abiru N., Eguchi K., Prevention of type 1 diabetes: From the view point of β cell damage, Diabetes Res. Clin. Pract., 2004, 66, S27–S32 http://dx.doi.org/10.1016/j.diabres.2003.09.015Google Scholar

  • [8] Rahimi R., Nikfar S., Larijani B., Abdollahi M., A review on the role of antioxidants in the management of diabetes and its complications, Biomed. Pharmacother., 2005, 59, 365–373 http://dx.doi.org/10.1016/j.biopha.2005.07.002CrossrefGoogle Scholar

  • [9] Jung C.H., Zhou S., Ding G.X., Kim J.H., Hong M.H., Shin Y.C., et al., Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic rats, Biosci. Biotechnol. Biochem., 2006, 70, 2556–2559 http://dx.doi.org/10.1271/bbb.60238CrossrefGoogle Scholar

  • [10] Hasani-Ranjbar Sh., Larijani B., Abdollahi M., A systematic review of Iranian medicinal plants useful in diabetes mellitus, Arch. Med. Sci., 2008, 4, 285–292 Google Scholar

  • [11] Pradhan S.C., Girish C., Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine, Indian J. Med. Res., 2006, 124, 491–504 Google Scholar

  • [12] Toklu H.Z., Tunali Akbay T., Velioglu-Ogunc A., Ercan F., Gedik N., Keyer-Uysal M., et al., Silymarin, the antioxidant component of Silybum marianum, prevents sepsis-induced acute lung and brain injury, J. Surg. Res., 2008,145, 214–222 http://dx.doi.org/10.1016/j.jss.2007.03.072CrossrefGoogle Scholar

  • [13] Guigas B., Naboulsi R., Villanueva G.R., Taleux N., Lopez-Novoa J.M., Leverve X.M., et al., The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase, Cell Physiol. Biochem., 2007, 20, 925–934 http://dx.doi.org/10.1159/000110453CrossrefGoogle Scholar

  • [14] Hussain S.A., Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes, J. Med. Food, 2007, 10, 543–547 http://dx.doi.org/10.1089/jmf.2006.089CrossrefGoogle Scholar

  • [15] Vengerovskii A.I., Khazanov V.A., Eskina K.A., Vasilyev K.Y., Effects of silymarin (hepatoprotector) and succinic acid (bioenergy regulator) on metabolic disorders in experimental diabetes mellitus, Bull. Exp. Biol. Med., 2007, 144, 53–56 http://dx.doi.org/10.1007/s10517-007-0252-2CrossrefGoogle Scholar

  • [16] Saller R., Meier R., Brignoli R., The use of silymarin in the treatment of liver diseases, Drugs, 2001, 61, 2035–2063 http://dx.doi.org/10.2165/00003495-200161140-00003CrossrefGoogle Scholar

  • [17] Esmaily H., Hosseini-Tabatabaei A., Rahimian R., Khorasani R., Baeeri M., Barazesh-Morgani A., et al., On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells, Cent. Eur. J. Biol., 2009, 4, 204–213 http://dx.doi.org/10.2478/s11535-008-0053-2CrossrefGoogle Scholar

  • [18] Koch H.P., Bachner J., Loffler E., Silymarin: potent inhibitor of cyclic AMP phosphodiesterase, Methods Find. Exp. Clin. Pharmacol., 1985, 7, 409–413 Google Scholar

  • [19] Beretz A., Anton R., Stoclet J.C., Flavonoid compounds are potent inhibitors, Experientia, 1978, 34, 1054–1055 http://dx.doi.org/10.1007/BF01915343CrossrefGoogle Scholar

  • [20] Milani E., Nikfar S., Khorasani R., Zamani M.J., Abdollahi M., Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats, Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2005, 140, 1054–1055 http://dx.doi.org/10.1016/j.cca.2005.02.010CrossrefGoogle Scholar

  • [21] Khoshakhlagh P., Bahrololoumi-Shapourabadi M., Mohammadirad A., Ashtaral-Nakhai L., Minaie B., Abdollahi M., Beneficial effect of phosphodiesterase-5 inhibitor in experimental inflammatory bowel disease; molecular evidence for involvement of oxidative stress, Toxicol. Mech. Methods, 2007, 17, 281–288 http://dx.doi.org/10.1080/15376510601003769CrossrefGoogle Scholar

  • [22] Zamani M.J., Sharifzadeh M., Rezaie A., Mashayekhi F., Abdollahi M., Effects of sildenafil on rat irritable bowel syndrome, Therapy, 2005, 2, 237–242 http://dx.doi.org/10.2217/14750708.2.2.237CrossrefGoogle Scholar

  • [23] Rainone F., Milk thistle, Am. Fam. Physician, 2005, 72, 1285–1288 Google Scholar

  • [24] Kang J.S., Jeon Y.J., Kim H.M., Han S.H., Yang K.H., Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages, J. Pharmacol. Exp. Ther., 2002, 302, 138–144 http://dx.doi.org/10.1124/jpet.302.1.138CrossrefGoogle Scholar

  • [25] Luper S., A review of plants used in the treatment of liver disease: part 1, Altern. Med. Rev., 1998, 3, 410–421 Google Scholar

  • [26] Kang J.S., Jeon Y.J., Park S.K., Yang K.H., Kim H.M., Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1beta and prostaglandin E2 synthesis by silymarin, Biochem. Pharmacol., 2004, 67, 175–181 http://dx.doi.org/10.1016/j.bcp.2003.08.032CrossrefGoogle Scholar

  • [27] Manna S.K., Mukhopadhyay A., Van N.T., Aggarwal B.B., Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis, J. Immunol., 1999, 163, 6800–6809 Google Scholar

  • [28] Hosseini-Tabatabaei A., Esmaily H., Rahimian R., Khorasani R., Baeeri M., Barazesh-Morgani A., et al., Benefit of nicorandil on an immunologic murine model of experimental colitis, Cent. Eur. J. Biol., 2009, 4, 74–85 http://dx.doi.org/10.2478/s11535-008-0047-0CrossrefGoogle Scholar

  • [29] Karabatas L.M., Pastorale C., de Bruno L.F., Maschi F., Pivetta O.H., Lombardo Y.B., et al., Early manifestations in multiple-low-dose streptozotocin-induced diabetes in mice, Pancreas, 2005, 30, 318–324 http://dx.doi.org/10.1097/01.mpa.0000161888.02244.7aCrossrefGoogle Scholar

  • [30] Astaneie F., Afshari M., Mojtahedi A., Mostafalou S., Zamani M.J., Larijani B., et al., Total antioxidant capacity and levels of epidermal growth factor and nitric oxide in blood and saliva of insulin-dependent diabetic patients, Arch. Med. Res., 2005, 36, 376–381 http://dx.doi.org/10.1016/j.arcmed.2005.03.007CrossrefGoogle Scholar

  • [31] Levine R.L., Garland D., Oliver C.N., Amici A., Climent I., Lenz A.G., et al., Determination of carbonyl content in oxidatively modified proteins, Methods Enzymol., 1990, 186, 464–478 http://dx.doi.org/10.1016/0076-6879(90)86141-HCrossrefGoogle Scholar

  • [32] Radfar M., Larijani B., Hadjibabaie M., Rajabipour B., Mojtahedi A., Abdollahi M., Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type-2 patients; a randomized, double-blind placebo-controlled clinical trial, Biomed. Pharmacother., 2005, 59, 302–306 http://dx.doi.org/10.1016/j.biopha.2005.05.003Google Scholar

  • [33] Hu M.L., Dillard C.J., Plasma SH and GSH measurement, Methods Enzymol., 1994, 233, 385–387 http://dx.doi.org/10.1016/S0076-6879(94)33045-XCrossrefGoogle Scholar

  • [34] Ashtaral-Nakhai L., Mohammadirad A., Yasa N., Minaie B., Nikfar S., Ghazanfari G., et al., Benefits of Zataria multiflora boiss in experimental model of mouse inflammatory bowel disease, Evid. Based Complement. Alternat. Med., 2007, 4, 43–50 http://dx.doi.org/10.1093/ecam/nel051CrossrefGoogle Scholar

  • [35] Bradfort M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding, Anal. Biochem., 1976, 72, 248–254 http://dx.doi.org/10.1016/0003-2697(76)90527-3CrossrefGoogle Scholar

  • [36] Soto C., Mena R., Luna J., Cerbon M., Larrieta E., Vital P., et al., Silymarin induces recovery of pancreatic function after alloxan damage in rats, Life Sci., 2004,75, 2167–2180 http://dx.doi.org/10.1016/j.lfs.2004.04.019CrossrefGoogle Scholar

  • [37] Soto C., Recoba R., Barron H., Alvarez C., Favari L., Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas, Comp. Biochem. Physiol. Part C., 2003,136, 205–212 http://dx.doi.org/10.1016/S1095-6433(03)00134-XCrossrefGoogle Scholar

  • [38] Soto C., Perez B.L., Favari L.P., Reyes J.L., Prevention of alloxan-induced diabetes mellitus in the rat by silymarin, Comp. Biochem. Physiol., 1998,119C,125–129 Google Scholar

  • [39] Afshari M., Larijani B., Rezaie A., Mojtahedi A., Zamani M.J., Astanehi-Asghari F., et al., Ineffectiveness of allopurinol in reduction of oxidative stress in diabetic patients; a randomized, double-blind placebo-controlled clinical trial, Biomed. Pharmacother., 2004, 58, 546–550 http://dx.doi.org/10.1016/j.biopha.2004.09.012CrossrefGoogle Scholar

  • [40] Rabinovitch A., Suarez-Pinzon W.L., Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus, Biochem. Pharmacol., 1998, 55, 1139–1149 http://dx.doi.org/10.1016/S0006-2952(97)00492-9CrossrefGoogle Scholar

  • [41] Maritim A.C., Sanders R.A., Watkins J.B.3rd., Diabetes, oxidative stress, and antioxidants: a review, J. Biochem. Mol. Toxicol., 2003, 17, 24–38 http://dx.doi.org/10.1002/jbt.10058CrossrefGoogle Scholar

  • [42] Hosseini-Tabatabaei A., Abdollahi M., Potassium channel openers and improvement of toxic stress: Do they have role in the management of inflammatory bowel disease?, Inflamm. Allergy Drug. Targets, 2008, 7, 129–135 http://dx.doi.org/10.2174/187152808785748164CrossrefGoogle Scholar

  • [43] Ansari G., Mojtahedzadeh M., Kajbaf F., Najafi A., Khajavi M.R., Khalili H., et al., How does blood glucose control with metformin influence intensive insulin protocols? Evidence for involvement of oxidative stress and inflammatory cytokines, Adv. Ther., 2008, 25, 681–702 http://dx.doi.org/10.1007/s12325-008-0075-1CrossrefGoogle Scholar

  • [44] Hadidi E., Mojtahedzadeh M., Paknejad M.H., Nikfar S., Zamani M.J., Sahraian M.A., et al., Alterations of blood IL-8, TGF-β1 and nitric oxide levels in relation to blood cells in patients with acute brain injury, Therapy, 2006, 3, 413–419 Google Scholar

  • [45] Matsuda T., Ferreri K., Todorov I., Kuroda Y., Smith C.V., Kandeel F., et al., Silymarin protects pancreatic beta-cells against cytokine-mediated toxicity: implication of c-Jun NH2-terminal kinase and janus kinase/signal transducer and activator of transcription pathways, Endocrinology, 2005, 146, 175–185 http://dx.doi.org/10.1210/en.2004-0850Google Scholar

  • [46] Ranjbar A., Khani-Jazani K., Sedighi A., Jalali-Mashayekhi F., Ghazi-Khansari M., Abdollahi M., Alteration of body total antioxidant capacity and thiol molecules in human chronic exposure to aluminium, Toxicol. Environ. Chem., 2008, 90, 707–713 http://dx.doi.org/10.1080/02772240701660650CrossrefGoogle Scholar

  • [47] Ramakrishna V., Jailkhani R., Evaluation of oxidative,e stress in insulin dependent diabetes mellitus (IDDM) patients, Diagn. Pathol., 2007, 2, 22 http://dx.doi.org/10.1186/1746-1596-2-22CrossrefGoogle Scholar

  • [48] Soleimani H., Ranjbar A., Baeeri M., Mohammadirad A., Khorasani R., Rat plasma oxidation status after Nigella sativa L. botanical treatment in CCL4-treated rats, Toxicol. Mech. Methods, 2008, 18, 725–731 http://dx.doi.org/10.1080/15376510802232233CrossrefGoogle Scholar

  • [49] Abdollahi M., Fooladian F., Emami B., Zafari K., Bahreini-Moghadam A., Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva, Hum. Exp. Toxicol., 2003, 22, 587–592 http://dx.doi.org/10.1191/0960327103ht399oaCrossrefGoogle Scholar

  • [50] Abdollahi M., Bahreini-Moghadam A., Emami B., Fooladian F., Zafari K., Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva, Comp. Biochem. Physiol. Toxicol. Pharmacol., 2003, 135C, 331–336 http://dx.doi.org/10.1016/S1532-0456(03)00120-0CrossrefGoogle Scholar

  • [51] Mohseni Salehi Monfared S.S., Larijani B., Abdollahi M., Islet transplantation and antioxidant management: a comprehensive review, World J. Gastroenterol., 2009, 15, 1153–1161 http://dx.doi.org/10.3748/wjg.15.1153CrossrefGoogle Scholar

  • [52] Hasani-Ranjbar S., Larijani B., Abdollahi M., A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases, Inflamm. Allergy Drug Targets, 2009, 8, 2–10 http://dx.doi.org/10.2174/187152809787582561CrossrefGoogle Scholar

About the article

Published Online: 2009-07-26

Published in Print: 2009-09-01

Citation Information: Open Life Sciences, Volume 4, Issue 3, Pages 369–380, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-009-0014-4.

Export Citation

© 2009 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Luminita Voroneanu, Ionut Nistor, Raluca Dumea, Mugurel Apetrii, and Adrian Covic
Journal of Diabetes Research, 2016, Volume 2016, Page 1
Hanieh Kamyab, Shohreh Hejrati, Mahnaz Khanavi, Farshad Malihi, Azadeh Mohammadirad, Maryam Baeeri, Hadi Esmaily, and Mohammad Abdollahi
Open Life Sciences, 2010, Volume 5, Number 3
Soodabeh Saeidnia and Mohammad Abdollahi
Toxicology and Applied Pharmacology, 2013, Volume 273, Number 3, Page 442
H.R. Rahimi, M. Gholami, H.R. Khorram-Kh, F. Gharibdoos, and M. Abdollahi
Asian Journal of Animal and Veterinary Advances, 2012, Volume 7, Number 1, Page 38
Pooneh Salari, Shekoufeh Nikfar, and Mohammad Abdollahi
International Journal of Pharmacology, 2011, Volume 7, Number 7, Page 749
Hadi Esmaily, Amanollah Vaziri-Bami, Amir Ebrahim Miroliaee, Maryam Baeeri, and Mohammad Abdollahi
Fundamental & Clinical Pharmacology, 2011, Volume 25, Number 6, Page 723
Asia Karim, Muhammad Nouman, Saba Munir, and Saba Sattar
International Journal of Pharmacology, 2011, Volume 7, Number 4, Page 419
Avin Mehri, Shirin Hasani-Ran, Bagher Larijani, and Mohammad Abdollahi
International Journal of Pharmacology, 2011, Volume 7, Number 2, Page 161
Amir Ebrahim Miroliaee, Hadi Esmaily, Amanollah Vaziri-Bami, Maryam Baeeri, Ahmad Reza Shahverdi, and Mohammad Abdollahi
Toxicology Mechanisms and Methods, 2011, Volume 21, Number 3, Page 200

Comments (0)

Please log in or register to comment.
Log in