Hypolipidemic, Hepatoprotective and Anti-inflammatory Role of Chios Mastic gum in Streptozotocin-induced Diabetic Mice with Fatty Liver Disease

Aspasia Tzani, Evanthia Bletsa, Ilias P Doulamis, Laskarina-Maria Korou, Panagiotis Konstantopoulos, Ioannis S Vlachos, Ioannis Georgiadis, Despina N Perrea


Aim: Non alcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease and it is highly prevalent in patients in patients with diabetes mellitus.  Chios Mastic gum (CMG) is known for its antioxidant and its potential hypolipidemic effects. This study sought to investigate the role of CMG in metabolic profile and liver histology in an animal model of NAFLD.

Material and Methods: A total of 37 streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were allocated into the following groups: Control group (n=13); LdM (n=12) animals receiving low dose mastic for 8 weeks (20 mg/Kg of body weight); HdM (n=12) animals receiving high dose mastic (500 mg/Kg BW) for the same period. Serum lipid and glucose levels were determined at baseline and at 4 and 8 weeks (end of experiment). Serum adiponectin, resistin and interleukin-6 levels were also measured at baseline and at the end of the experiment. Histopathological examination for liver was performed.

Results: After 4 weeks, CMG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM groups. At the end of the experiment, LdM presented significantly lower serum glucose and ameliorated lipidemic profile compared with control group. Adiponectin and resistin levels at the end of the experiment did not differ between control and both treated groups, while interleukin-6 was significantly lower in LdM group compared with the control group. Hepatic steatosis observed in control group was partially reversed in both CMG groups.

Conclusions: CMG administration in low dosages improves metabolic disturbances and exerts anti-inflammatory properties in diabetic mice while alleviating hepatic damage.


Chios mastic gum; diabetes; lipid metabolism; mice; non-alcoholic fatty-liver disease; interleukin-6

Full Text:



Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic medicine : a journal of the British Diabetic Association. Jul 1998;15(7):539-553.

Baxter M. Treatment of type 2 diabetes: a structured management plan. Advances in therapy. Feb 2008;25(2):106-114.

Leite NC, Villela-Nogueira CA, Cardoso CR, Salles GF. Non-alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment. World journal of gastroenterology. Jul 14 2014;20(26):8377-8392.

Nascimbeni F, Aron-Wisnewsky J, Pais R, et al. Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease. BMJ open gastroenterology. 2016;3(1):e000075.

Dimas KS, Pantazis P, Ramanujam R. Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse pharmaceutical and biomedical properties. In vivo. Sep-Oct 2012;26(5):777-785.

Papalois A, Gioxari A, Kaliora AC, et al. Chios mastic fractions in experimental colitis: implication of the nuclear factor kappaB pathway in cultured HT29 cells. Journal of medicinal food. Nov 2012;15(11):974-983.

Paraschos S, Magiatis P, Mitakou S, et al. In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrobial agents and chemotherapy. Feb 2007;51(2):551-559.

Li S, Cha IH, Nam W. Chios mastic gum extracts as a potent antitumor agent that inhibits growth and induces apoptosis of oral cancer cells. Asian Pacific journal of cancer prevention : APJCP. 2011;12(7):1877-1880.

Loizou S, Paraschos S, Mitakou S, Chrousos GP, Lekakis I, Moutsatsou P. Chios mastic gum extract and isolated phytosterol tirucallol exhibit anti-inflammatory activity in human aortic endothelial cells. Experimental biology and medicine. May 2009;234(5):553-561.

Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation. Phytotherapy research : PTR. May 2003;17(5):501-507.

Georgiadis I, Karatzas T, Korou LM, Katsilambros N, Perrea D. Beneficial health effects of Chios Gum Mastic and peroxisome proliferator-activated receptors: indications of common mechanisms. Journal of medicinal food. Jan 2015;18(1):1-10.

Vallianou I, Peroulis N, Pantazis P, Hadzopoulou-Cladaras M. Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity. PloS one. 2011;6(11):e20516.

Kartalis A, Didagelos M, Georgiadis I, et al. Effects of Chios mastic gum on cholesterol and glucose levels of healthy volunteers: A prospective, randomized, placebo-controlled, pilot study (CHIOS-MASTIHA). European journal of preventive cardiology. May 2016;23(7):722-729.

. Guide for the Care and Use of Laboratory Animals. Washington (DC)1996.

Korou LM, Agrogiannis G, Koros C, et al. Impact of N-acetylcysteine and sesame oil on lipid metabolism and hypothalamic-pituitary-adrenal axis homeostasis in middle-aged hypercholesterolemic mice. Scientific reports. 2014;4:6806.

Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B. Effects of Cinnamon, Cardamom, Saffron, and Ginger Consumption on Markers of Glycemic Control, Lipid Profile, Oxidative Stress, and Inflammation in Type 2 Diabetes Patients. The review of diabetic studies : RDS. Fall-Winter 2014;11(3-4):258-266.

Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes care. Sep 1989;12(8):553-564.

Morrow TJ. Animal models of painful diabetic neuropathy: the STZ rat model. Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.]. Nov 2004;Chapter 9:Unit 9 18.

Skovso S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. Journal of diabetes investigation. Jul 2014;5(4):349-358.

Imajo K, Yoneda M, Kessoku T, et al. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. International journal of molecular sciences. 2013;14(11):21833-21857.

Paraschos S, Mitakou S, Skaltsounis AL. Chios gum mastic: A review of its biological activities. Current medicinal chemistry. 2012;19(14):2292-2302.

Lemonakis N, Magiatis P, Kostomitsopoulos N, Skaltsounis AL, Tamvakopoulos C. Oral administration of chios mastic gum or extracts in mice: quantification of triterpenic acids by liquid chromatography-tandem mass spectrometry. Planta medica. Nov 2011;77(17):1916-1923.

Katsanou ES, Kyriakopoulou K, Emmanouil C, Fokialakis N, Skaltsounis AL, Machera K. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats. PloS one. 2014;9(6):e100190.

Leite NC, Villela-Nogueira CA, Pannain VL, et al. Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors. Liver international : official journal of the International Association for the Study of the Liver. May 2011;31(5):700-706.

Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Annals of medicine. Dec 2011;43(8):617-649.

Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation. Sultan Qaboos University medical journal. May 2016;16(2):e132-141.

Polyzos SA, Kountouras J, Polymerou V, Papadimitriou KG, Zavos C, Katsinelos P. Vaspin, resistin, retinol-binding protein-4, interleukin-1alpha and interleukin-6 in patients with nonalcoholic fatty liver disease. Annals of hepatology. Sep-Oct 2016;15(5):705-714.

Amarapurka DN, Amarapurkar AD, Patel ND, et al. Nonalcoholic steatohepatitis (NASH) with diabetes: predictors of liver fibrosis. Annals of hepatology. Jan-Mar 2006;5(1):30-33.

Triantafyllou A, Bikineyeva A, Dikalova A, Nazarewicz R, Lerakis S, Dikalov S. Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress. Nutrition journal. 2011;10:64.

Manna P, Das J, Ghosh J, Sil PC. Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF-kappaB, MAPKs, and mitochondria-dependent pathways: Prophylactic role of arjunolic acid. Free radical biology & medicine. Jun 1 2010;48(11):1465-1484.

Grigorescu M, Crisan D, Radu C, Grigorescu MD, Sparchez Z, Serban A. A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. Aug 2012;63(4):347-353.

Chu CJ, Lu RH, Wang SS, et al. Plasma levels of interleukin-6 and interleukin-8 in Chinese patients with non-alcoholic fatty liver disease. Hepato-gastroenterology. Oct-Nov 2007;54(79):2045-2048.

Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. Nov 2003;52(11):2784-2789.

Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. The American journal of gastroenterology. Jun 2008;103(6):1372-1379.

Tzanetakou IP, Doulamis IP, Korou LM, et al. Water Soluble Vitamin E Administration in Wistar Rats with Non-alcoholic Fatty Liver Disease. The open cardiovascular medicine journal. 2012;6:88-97.

Jamali R, Razavizade M, Arj A, Aarabi MH. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. World journal of gastroenterology. Jun 7 2016;22(21):5096-5103.

Tarantino G, Savastano S, Colao A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World journal of gastroenterology. Oct 14 2010;16(38):4773-4783.

Triantafyllou A, Chaviaras N, Sergentanis TN, Protopapa E, Tsaknis J. Chios mastic gum modulates serum biochemical parameters in a human population. Journal of ethnopharmacology. Apr 20 2007;111(1):43-49.

DOI: http://dx.doi.org/10.23803/hja.v7i4.87

DOI (PDF): http://dx.doi.org/10.23803/hja.v7i4.87.g61


  • There are currently no refbacks.