Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase

Authors

  • Mirjana Mihailović Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-8097-1186
  • Aleksandra Uskoković Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-9616-1102
  • Jelena Arambašic Jovanović Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-8810-0668
  • Nevena Grdović Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0003-1504-4578
  • Svetlana Dinić Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-7612-3117
  • Goran Poznanović Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0003-0839-7017
  • Aida Franić Clinical Hospital Center Rijeka, Department of Transfusion Medicine, Tome Stizica 3, 51000 Rijeka
  • Marija Đorđević Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0001-9051-9583
  • Melita Vidaković Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0001-8410-6264

Keywords:

diabetes, Castanea sativa, Lactarius deterrimus, antioxidants, hepatoprotection

Abstract

Paper description:

  • The effects of Castanea sativa and Lactarius deterrimus extracts on the mechanisms of hepatoprotection in streptozotocin-induced diabetic rats were studied.
  • Both extracts caused activation of the prosurvival-Akt kinase and decreases in O-GlcNAc-modified antioxidant enzymes and NF-κB, collagen fiber deposition, and proinflammatory signaling.
  • The hyperglycemia-reducing and antioxidant effects of the extracts suppressed cytotoxic signaling pathways and attenuated diabetes complications in the liver.
  • The extracts are beneficial in the prevention of liver damage. The extracts could be considered for prediabetes and diabetes management after a definitive phytochemical description of extract constituents and their evaluation in preclinical and clinical studies.


Abstract: Diabetes is the most important non-infectious disease affecting 5% of the general population. Different plant and mushroom extracts with hypoglycemic and antioxidant properties have been used traditionally as antidiabetic herbal medicines. The aim of this study was to study the in vivo effect of extracts obtained from the edible mushroom, Lactarius deterrimus (Ld), and chestnut, Castanea sativa (Cs), on the alleviation of liver damage in streptozotocin (STZ)-induced diabetic rats. The extracts were applied, either alone or in combination, for four weeks, starting from the last day of STZ administration. Diabetic rats treated with the extracts exhibited reduced hyperglycemia and lower hepatic oxidative stress. Extract treatment decreased the level of O-linkage of N-acetylglucosamine modified superoxide dismutase, catalase and NF-κB. Masson trichrome staining showed a decrease in collagen fiber deposition in the liver. Immunoblot analysis revealed the activation of the prosurvival Akt kinase after extract application. The obtained results revealed that the hyperglycemia-reducing and antioxidant effects of the Ld and Cs extracts suppressed cytotoxic signaling pathways, attenuating the negative effects of diabetes on the liver. The examined extracts are beneficial in the prevention of liver damage and could be considered for prediabetes and diabetes management after a definitive phytochemical description of extract constituents and subsequent evaluation in preclinical and clinical studies.

https://doi.org/10.2298/ABS200410017M

Received: April 10, 2020; Revised: April 18, 2020; Accepted: April 20, 2020; Published online: April 22, 2020

How to cite this article: Mihailović M, Uskoković A, Arambašić Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, VidakovićM. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci. 2020;72(2):233-42.

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Author Biography

Melita Vidaković, Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade


References

Lucchesi AN, Tavares de Freitas N, Cassettari L, Marques SFG, Spadella CT. Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a mechanism for diabetic chronic liver disease. Acta Cir Bras. 2013;28:502-8.

Oter S, Jin S, Cucullo L, Dorman HJD. Oxidants and antioxidants: friends or foes? Oxid Antioxid Med Sci. 2012;1:1-4.

Trief PM, Cibula D, Rodriguez E, Akel B, Weinstock RS. Incorrect Insulin Administration: A Problem That Warrants Attention. Clin Diabetes. 2016;34(1):25-33.

Mukherjee PK, Maiti K, Mukherjee K, Houghton PJ. Leads from Indian medicinal plants with hypoglycemic potentials. J Ethopharm. 2006;106:1-28.

Saeed N, Khan RM, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med. 2012;12:221.

Sanz M, Cadahìa E, Esteruelas E, Muñoz AM, de Simón F, Hernández T, Estrella I. Phenolic compounds in chestnut (Castanea sativa Mill.) heartwood. Effect of toasting at cooperage. J Agric Food Chem. 2010;58:9631-40.

Mujić A, Grdović N, Mujić I, Mihailović M, Živković J, Poznanović G, Vidaković M. Antioxidative effects of phenolic extracts from chestnut leaves, catkins and spiny burs in streptozotocin-treated rat pancreatic β-cells. Food Chem. 2011;125:841-9.

Lupini C, Cecchinato M, Scagliarini A, Graziani R, Catelli E. In vitro antiviral activity of chestnut and quebracho woods extracts against avian reovirus and metapneumovirus. Res Vet Sci. 2009;87:482-7.

Grdović N, Dinić S, Arambašić J, Mihailović M, Uskoković A, Marković J, Poznanović G, Vidović S, Zeković Z, Mujić A, Mujić I, Vidaković M. Protective effect of Lactarius deterrimus and Castanea sativa extract mix(MIX Ld/Cs) on STZ-induced oxidative stress and pancreatic beta-cell death. Brit J Nutrit. 2012;108:1163-76.

Lo HC, Wasser SP. Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems. Int J Med Mushrooms. 2011;13:401-426.

Jayakumar T, Ramesh E, Geraldine P. Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCL4-induced liver injury in rats. Food Chem Toxicol. 2006;44:1989-96.

Hou Y, Ding X, Hou H, Song B, Wang T, Wang F, Zhong J. Immunostimulant activity of a novel polysaccharide isolated from Lactarius deliciosus (l. ex fr.) gray. Ind J Pharmacol. 2013;75:393-9.

Athanasakis G, Aligianni N, Gonou-Zagou Z, Skaltsounis AL., Fokialakis N. Antioxidant properties of the wild edible mushroom Lactarius salmonicolor. J Med Food. 2013;16:760-4.

Mihailović M, Arambašić Јovanović J, Uskoković A, Grdović N, Dinić S, Vidović S, Poznanović G, Mujić I, Vidaković M. Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats. J Diabet Res. 2015;2015:576726.

Arambašić Jovanović J, Mihailović M, Uskoković A, Grdović N, Dinić S, Poznanović G, Mujić I, Vidaković M. Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats. Front Pharmacol. 2017;8:793.

Drabkin D, Austin H. Spectrophotometric studies preparations from washed blood cells. J Biolog Chem 1935;112:51-5.

Parker KM, England JD, Da Costa J, Hess EL, Goldstein DE. Improved colorimetric assay for glycosylated haemoglobin. Clin Chem. 1981;27:669-72.

Sedlak J, Lindsay RH. Estimation of total, protein bound and non-protein bound sulfhydryl groups in tissue with Elman’s reagent. Anal Biochem. 1968;25:192-205.

Ellman CL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70-7.

Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and simple assay for superoxide dismutase. J Biolog Chem. 1972;247:3170-5.

Beutler E. Catalase. In: Beutler E, editor. Red cell metabolism. A manual of biochemical methods. New York: Grune and Stratton Inc.; 1982. p. 105-16.

Gandy JC, Rountree AE, Bijur GN. Akt1 is dynamically modified with O-GlcNAc following treatments with PUGNAc and insulin-like growth factor-1. FEBS Lett. 2006;580:3051-8.

Drury RA, Wallington EA, Cancerson R. Carlton’s Histopathological Techniques. 4 th ed. Oxford, London, New York: Oxford University press; 1976.

Guven A, Yavuz O, Cam M, Ercan F, Bukan N, Comunoglu C, Gokce F. Effects of melatonin on streptozotocin-induced diabetic liver injury in rats. Acta Histochem. 2006;108:85-93.

Ma J, Hart GW. Protein O-GlcNAcylation in diabetes and diabetic complications. Expert Rev Proteom. 2013;10:365-80.

Dinić S, Arambašić J, Mihailović M, Uskoković A, Grdović N, Marković J, Karadžić B, Poznanović G, Vidaković M. Decreased O-GlcNAcylation of the key proteins in kinase and redox signaling pathways is a novel mechanism of the beneficial effect of alpha-lipoic acid in diabetic liver. Brit J Nutrit. 2013;110:401-12.

Zhang B, Kang M, Xie Q, Xu B, Sun C, Chen K, Wu Y. Anthocyanins from Chinese bayberry extract protect β cells from oxidative stress-mediated injury via HO-1 upregulation. J Agric Food Chem. 2011;59:537-45.

Jackson LN, Larson SD, Silva SR, Rychahou PG, Chen LA, Qiu S, Rajaraman S, Evers BM. PI3K/Akt activation is critical for early hepatic regeneration after partial hepatectomy. Am J Physiol. 2008;294:1401-10.

Niehof M, Streetz K, Rakemann T, Bischoff SC, Manns MP, Horni F, Trautwein C. Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPb promoter suggests a new mechanism of transcriptional regulation by STAT3. J Biolog Chem. 2011;276:9016-27.

Choudhari SR, Khan MA, Harris G, Picker D, Jacob GS, Block T, Shailubha K.. Deactivation of Akt and STAT3 signaling promotes apoptosis, inhibits proliferation, and enhances the sensitivity of hepatocellular carcinoma cells to an anticancer agent Atiprimod. Mol Cancer Ther. 2007;6:112-21.

Patra K, Jana S, Mandal DP, Bhattacharjee S. Evaluation of the antioxidant activity of extracts and active principles of commonly consumed Indian spices. J. Environ. Pathol Toxicol Oncol. 2016;35:299-315.

Pinelo M, Manzocco L, Nunez MJ, Nicoli MC. Interaction among phenols in food fortification: negative synergism on antioxidant capacity. J Agric Food Chem. 2004;54:1177-80.

Vieira V, Marques A, Barros L, Barreira JCM, Ferreira I. Insights in the antioxidant synergistic effects of combined edible mushrooms: phenolic and polysaccharidic extracts of Boletus edulis and Marasmius oreades. J Food Nutr Res. 2012;51:109-16.

Nedamani ER, Mahoonak AS, Ghorbani M, Kashaninejad M. Antioxidant properties of individual vs. combined extracts of rosemary leaves and oak fruit. J Agric Sci Technol. 2014;16:1575-86.

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Published

2020-07-01

How to Cite

1.
Mihailović M, Uskoković A, Arambašic Jovanović J, Grdović N, Dinić S, Poznanović G, Franić A, Đorđević M, Vidaković M. Treatment of streptozotocin-induced diabetic rats with Castanea sativa and Lactarius deterrimus extracts decreases liver damage by initiating activation of the Akt prosurvival kinase. Arch Biol Sci [Internet]. 2020Jul.1 [cited 2022Aug.7];72(2):233-42. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/5249

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