Deneysel Diyabet Oluşturulan Ratlarda Glisirizin'in Antienflamatuar ve Antioksidan Etkilerinin Araştırılması

Year 2019, Volume: 2 Issue: 2, 72 - 79, 29.05.2019

Mehmet Mustafa İşgör , Altuğ Küçükgül , Gonca Ozan Kocamüftüoğlu Hayrettin Ata

Abstract

Diyabet, günümüzde dünya çapında önemli bir yaygınlığa sahip metabolik bir hastalıktır. Adipoz dokudan salgılanan adipokinlerin, insülin sinyal iletiminde görev aldığı ve glikoz metabolizmasının düzenlenmesinde etkilerinin olduğu bilinmektedir. Meyan kökünün primer biyoaktif bileşeni olan glisirizinin anti-inflamatuar ve anti-oksidan etkileri olduğu birçok araştırmada rapor edilmiştir. Bu çalışmada deneysel olarak oluşturulan in vivo diyabet modelinde glisirizin’in oksidatif stres ve inflamasyon üzerine biyoetkinliğinin araştırılması amaçlanmıştır. Araştırmamızda, ratlarda streptozotosin uygulamasını takiben 6 haftalık süre sonunda deneysel diyabet modeli oluşturuldu. Deney hayvanları her biri 8 tane rattan oluşacak şekilde kontrol grubu (Kont), diyabet grubu (DM), diyabet + glisirizin grubu (+Gly) ve glisirizin grubu (Gly) olmak üzere dört gruba ayrıldı. Glisirizin suda çözdürüldü ve 1 hafta süreyle ratlara 50 mg/kg/gün oral olarak verildi. Deneme sonunda, alınan adipoz ve karaciğer doku örnekleri homojenize edilerek total antioksidan ve oksidan kapasite spektrofotometrik analizlerle ortaya konuldu. Bununla birlikte, elde edilen RNA örneklerinden leptin ve adiponektin sitokinlerinin gen ifadeleri transkripsiyon düzeyinde gerçek zamanlı polimeraz zincir reaksiyonu (qRT-PCR) tekniği kullanılarak araştırıldı. Araştırmadan elde edilen verilere göre her iki dokuda glisirizinin diyabetle uyarılan total oksidan seviyelerini (TOS) anlamlı düzeyde azalttığı tespit edildi. Bunun yanı sıra, diyabetle azalan total antioksidan seviyelerinin (TAS) ise glisirizin uygulanımı ile anlamlı düzeyde attırdığı da bulundu. Yine, her iki dokuda adiponektin gen ekspresyonu DM grubunda kontrole göre aşağı-regüle olduğu, diyabet ile birlikte glisirizin uygulanan grupta ise DM grubuna göre yukarı-regüle olduğu belirlenmiştir. Bununla birlikte diyabet oluşturulan ratlarda gerek adipoz doku gerekse karaciğer dokusunda leptin ekspresyon ve protein seviyeleri artarken, glisirizinin bu etkiyi azalttığı görülmüştür. Özetle, glisirizin diyabetik ratların karaciğer ve adipoz dokularında sitokin seviyelerini düzenleyerek antienflamatuar etki göstermiştir. Ayrıca, antioksidan kapasiteyi de anlamlı düzeyde arttırarak antioksidan etkinlik göstermiştir.

Keywords

Diyabet, Glisirizin, İnflamasyon, Oksidatif stres

Investigation of Antiinflammatory and Antioxidant Effects of Glycyrrhizin on Rats with Experimental Diabetes

Abstract

Diabetes is a metabolic disease with a worldwide prevalence. Adipokines secreted from adipose tissue are known to be involved in insulin signal transduction and have an effect on the regulation of glucose metabolism. It has been reported in many studies that glycyrrhizin, the primary bioactive component of licorice root, has anti-inflammatory and anti-oxidant effects. In this study, it was aimed to investigate the bioactivity of glycyrrizine on oxidative stress and inflammation in an experimentally induced in vivo diabetes model. In our study, experimental diabetes model was formed at the end of 6 weeks following the administration of streptozotocin in rats. The experimental animals were divided into four groups, each consisting of 8 rats, the control group (Cont), the diabetes group (DM), the diabetes + glycyrrhizin group (+ Gly) and the glycyrrizine group (Gly). Glycyrrhizin was dissolved in water and rats were given orally at 50 mg / kg / day for one week. At the end of the experiment, adipose and liver tissue samples were homogenized and oxidative stress index, total antioxidant and oxidant capacity were determined by spectrophotometric analysis. Besides, gene expression levels of leptin and adiponectin from the obtained RNA samples were investigated at the transcription level by using the real-time polymerase chain reaction (qRT-PCR) technique. According to the data obtained from the study, it was determined that glycyrrhizin significantly reduced diabetic induced total oxidant status (TOS) levels in both tissues. In addition, it was found that level of total antioxidant status (TAS) decreased by diabetes was significantly increased with glycyrrhizin administration. Again, adiponectin gene expression in both tissues was down-regulated in the DM group compared to control, in glycyrrhizin treated diabetes group, up-regulation of the same gene was determined according to DM group. Moreover, leptin mRNA expressions increased in both adipose tissue and liver tissue in diabetic rats, whereas glycyrrhizin decreased this effect in adipose tissue, but a slight increase was observed in the liver tissue according DM group. In short, glycyrrhizin showed an anti-inflammatory effect by regulating cytokine levels in liver and adipose tissues of diabetic rats. Besides, it has an antioxidant effect by increasing the antioxidant capacity significantly.

Keywords

Diabetes, Glycyrrhizin, Inflammation, Oxidative stress

References

• Abdel-Ghffar EAA. (2016). Ameliorative effect of glabridin, a main component of Glycyrrhiza glabra L. roots in streptozotocin induced Type 1 diabetes in male albino rats. Indian Journal of Traditional Knowledge, 15 (4): 570-579.
• Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun, 257: 79–83.
• Bluher M. (2009). Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes, 117 (6): 241-50. Chandramouli C, Yong ST, Lam YL, Ton SH, Kadir KA. (2011). Glycyrrhizic acid improves lipid and glucose metabolism in high-sucrose-fed rats. J. Endocrinol Metab, 1: 125-141.
• Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. (2013). Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med, 378657.
• Cheng HS, Yaw HP, Ton SH, Choy SM, Kong JM, Abdul Kadir K. (2016). Glycyrrhizic acid prevents high calorie dietinduced metabolic aberrations despite the suppression of peroxisome proliferator-activated receptor γ expression. Nutrition, 32 (9): 995-1001.
• Duzguner V, Kucukgul A, Erdogan S, Celik S, Sahin K. (2008). Effect of Lycopene Administration on Plasma Glucose, Oxidative Stress and Body Weight in Streptozotocin Diabetic Rats. J Appl Him Res, 33: 17-20.
• Farooq R, Amin S, Hayat BM, Malik R, Wani HA, Majid S. (2017). Type 2 diabetes and metabolic syndrome- adipokine levels and effect of drugs. Gynecol Endocrinol, 33: 75–78.
• Galic S, Oakhill JS, Steinberg GR. (2010). Adipose tissue as an endocrine organ. Mol Cell Endocrinol, 316 (2): 129-39.
• Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. (2000). Plasma concentrations of a novel, adipose-specific protein, adiponectin in type 2 diabetic patients. Arterioscler Thromb Vasc Biol, 20: 1595–1599.
• Karthikesan K, Pari L, Menon VP. (2010). Protective effect of tetrahydrocurcumin and chlorogenic acid against streptozotocin – nicotinamide generated oxidative stress induced diabetes. J Funct Foods, 2: 134-42.
• Kataya HH, Hamza AA, Ramadan GA, Khasawneh MA. (2011). Effect of licorice extract on the complications of diabetes nephropathy in rats. Drug Chem Toxicol, 34 (2): 101-8.
• Katsiki N, Mantzoros C, Mikhailidis DP. (2017). Adiponectin, lipids and atherosclerosis. Curr Opin Lipidol, 28: 347–354.
• Kaur R, Kaur H, Dhindsa AS. (2013). Glycyrrhiza glabra: a phytopharmacological review. Int J Pharmaceut Sci Res, 4 (7): 2470-7.
• Khanahmadi M, Naghdi BH, Akhondzadeh S, Khalighi–Sigaroodi F, Mehrafarin A, Shahriari S, Hajiaghaee R. (2013). A Review on Medicinal Plant of Glycyrrhiza glabra L. J Med Plant Res, 2 (46): 1-12.
• Kolberg JA, Jørgensen T, Gerwien RW, Hamren S, McKenna MP, Moler E, Rowe MW, Urdea MS, Xu XM, Hansen T, Pedersen O, Borch-Johnsen K. (2009). Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort. Diabetes Care, 32 (7): 1207–1212.
• Li RY, Song HD, Shi WJ, Hu SM, Yang YS, Tang JF, Chen MD, Chen JL. (2004). Galanin inhibits leptin expression and secretion in rat adipose tissue and 3T3-L1 adipocytes. JMol Endocrinol, 33(1): 11-9.
• Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. (2016). Adiponectin, TNF-a and inflammatory cytokines and risk of type 2 diabetes: a systematic review and metaanalysis. Cytokine, 86: 100–109.
• López-Jaramillo P, Gómez-Arbeláez D, López-López J, López-López C, Martínez-Ortega J, Gómez-Rodríguez A, Triana-Cubillos S. (2014). The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Horm Mol Biol Clin Investig, 18: 37–45.
• Madhikarmi NL, Murthy KR, Rajagopal G, Singh PP. (2013). Lipid peroxidation and antioxidant status in patients with type 2 diabetes in relation to obesity in Pokhara – Nepal. J Diabetology, 4 (1): 5.
• Malik ZA, Sharma PL. (2011). An ethanolic extract from licorice (glycyrrhiza glabra) exhibits anti-obesity effects by decreasing dietary fat absorption in a high fat dietinduced obesity rat model. Int J Pharmaceut Sci Res, 2 (11): 3010-3.
• Minikoshi Y, Kim Y, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB. (2002). Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature, 415: 339-343.
• Mohammed FZ, El-Deen Al-Hussaini AS, El-Shehabi MS. (2015). Antidiabetic activity of caffeic acid and 18β-glycyrrhetinic acid and its relationship with the antioxidant property. Asian Journal of Pharmaceutical and Clinical Research, 8 (5): 229-235.
• Nagai Y, Ichihara A, Nakano D, Kimura S, Pelisch N, Fujisawa Y, Hitomi H, Hosomi N, Kiyomoto H, Kohno M, Ito H, Nishiyama A. (2009). Possible contribution of the nonproteolytic activation of prorenin to the developmentof insulin resistance in fructose-fed rats. Exp Physiol, 94(9):1016-23. doi: 10.1113/expphysiol.2009.048108.
• Poulos SP, Hausman DB, Hausman GJ. (2010). The development and endocrine functions of adipose tissue. Mol Cell Endocrinol, 323 (1): 20-34. Prajapati S, Patel BR. (2013). Phyto Pharmacological Perspective of Yashtimadhu Glycyrrhiza Glabra LINN A Review. Int J Pharm Biol Arch, 4 (5): 833-41.
• Rodger W. (1991). Non-insulin-dependent (type II) diabetes mellitus. Canadian Medical Association Journal, 145 (12): 1571–1581.
• Ruhl R, Landrier JF. (2016). Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormonereceptors. Mol Nutr Food Res, 60: 175–184.
• Sattar N. (2012). Biomarkers for diabetes prediction, pathogenesis or pharmacotherapy guidance? Past, present and future possibilities. Diabetic Medicine, 29 (1): 5-13.
• Shen Q, Pierce JD. (2015). Supplementation of coenzyme Q10 among patients with type 2 diabetes mellitus. Healthcare, 3: 296–309.
• Sil R, Ray D, Chakraborti AS. (2013). Glisirizin amelioratesinsulin resistance, hyperglycemia, dyslipidemia and oxidative stres in fructose-induced metabolic syndrome X in rat model. Indian Journal of Experimental Biology, 51: 129-138.
• Surampudi PN, John-Kalarickal J and Fonseca VA. (2009).Emerging concepts in the pathophysiology of type 2 diabetes mellitus. Mount Sinai Journal of Medicine, 76 (3):216–226.
• Usui I, Fujisaka S, Yamazaki K, Takano A, Murakami S, Yamazaki Y, Urakaze M, Hachiya H, Takata M, Senda S, Iwata M, Satoh A, Sasoaka T, Ak ND, Temaru R, Kobayashi M. (2007). Telmisartan reduced blood pressure and HOMAIR with increasing plasma leptin level in hypertensive and type 2 diabetic patients. Diabetes Res Clin Pract 77 (2):210-4.
• Wild S, Roglic G, Green A, Sicree R, King H. (2004). Global prevalence of diabetes: estimates for 2000 and projections for 2030. Diabetes Care, 27 (5): 1047–53.