Open Access Journal Article

Ursolic acid and rosiglitazone combination prevent low-grade inflammation and hepatic insulin resistance by modulating cytokine expression in mice fed a high-fat diet

by Arjunan Sundaresan 1,2,* Thangaiyan Radhiga 1  and  Kodukkur Viswanathan Pugalendi 1
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India
Department of Biochemistry, PRIST Deemed To Be University, Thanjavur - 613403, Tamil Nadu, India
Author to whom correspondence should be addressed.
IJCMR  2023, 13; 1(3), 13;
Received: 17 September 2023 / Accepted: 29 October 2023 / Published Online: 1 November 2023



The objective of this research endeavor was to assess the effects of rosiglitazone (RSG) and ursolic acid (UA) on hepatic insulin signaling indicators and inflammatory marker concentrations in C57/BL/6J mice that were provided with a high-fat diet (HFD).


C57BL/6J mice were fed a HFD for 16 weeks and orally administered UA (5 mg/kg BW), RSG (4 mg/kg BW), and UA (5 mg/kg BW) + RSG (4 mg/kg BW) for the last 6 weeks.


The HFD groups showed a significant increase in leptin, TNF-α, and IL-6, whereas adiponection level significantly decreased. The expression of insulin signaling markers in the liver also significantly increased in HFD mice.


Combination treatment improves above said parameters than individual parameters. These data suggest that combination treatment (UA with RSG) has potential benefits for the treatment of HFD-induced insulin resistance, and its effects may be associated with improvements in the inhibition of the expression of inflammatory markers in plasma and liver.

Copyright: © 2023 by Sundaresan, Radhiga and Pugalendi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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ACS Style
Sundaresan, A.; Radhiga, T.; Pugalendi, K. V. Ursolic acid and rosiglitazone combination prevent low-grade inflammation and hepatic insulin resistance by modulating cytokine expression in mice fed a high-fat diet. International Journal of Clinical Medical Research, 2023, 1, 13.
AMA Style
Sundaresan A, Radhiga T, Pugalendi K V. Ursolic acid and rosiglitazone combination prevent low-grade inflammation and hepatic insulin resistance by modulating cytokine expression in mice fed a high-fat diet. International Journal of Clinical Medical Research; 2023, 1(3):13.
Chicago/Turabian Style
Sundaresan, Arjunan; Radhiga, Thangaiyan; Pugalendi, Kodukkur V. 2023. "Ursolic acid and rosiglitazone combination prevent low-grade inflammation and hepatic insulin resistance by modulating cytokine expression in mice fed a high-fat diet" International Journal of Clinical Medical Research 1, no.3:13.

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  1. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Abingdon). 2014; 42(12):698-702.
  2. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103(2): 137-49.
  3. Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228–236.
  4. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes, J. Clin. Invest. 115 (2005) 1111–1119.
  5. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease, Nat. Rev. Immunol. 11 (2011) 98–107.
  6. Hauner H. Secretory factors from human adipose tissue and their functional role. Proc. Nutr. Soc. 2005;64:163–169.
  7. Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr. 2006;83:S461–5.
  8. Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008; 34(1): 2-11.
  9. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010; 72: 219-46.
  10. Snel M, van Diepen JA, Stijnen T, Pijl H, Romijn JA, Meinders AE, Voshol P, Jazet IM. Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetic patients. Food Chem Toxicol. 2011; 49(12): 3104-11.
  11. Sohn, K.H., Lee, H.Y., Chung, H.Y., Young, H.S., Yi, S.Y., Kim, K.W., 1995. Anti-angiogenic activity of triterpene acids. Cancer Lett. 94(2), 213-218.
  12. Liu, J., 1995. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol. 49(2) 57-68.
  13. Somova, L.O., Nadar, A., Rammanan, P., Shode, F.O., 2003. Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension.
  14. Malinowski, J.M., Bolesta, S., 2000. Rosiglitazone in the treatment of type 2 diabetes mellitus: a critical review, Clin. Ther. 22(10), 1151-1168.
  15. Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 2012;15:635–645.
  16. Sheedfar F, Di Biase S, Koonen D, Vinciguerra M. Liver diseases and aging: friends or foes? Aging Cell. 2013;12:950–954.
  17. Maratos-Flier E. The long reach of leptin. Nat Med. 2008; 14(6):604-6.
  18. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R and Ranganathan S, Kern, P.A. & Friedman, J.M. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1: 1155-1161, 1995
  19. Frago LM, Chowen JA. Hypothalamic leptin and ghrelin signaling as targets for improvement in metabolic control. Curr Pharm Des (2015) 21:3596–605.
  20. Shimizu H, Tsuchiya T, Sato N, Shimomura Y, Kobayashi I, Mori M. Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients. Diabetes Care. 1998; 21(9):1470-4.
  21. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, Xu A. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007; 53(1):34-41.
  22. Sundaresan A, Harini R, Pugalendi KV. Ursolic acid and rosiglitazone combination alleviates metabolic syndrome in high fat diet fed C57BL/6J mice. Gen Physiol Biophys. 2012; 31(3): 323-333.
  23. Xu, A.; Wang, H.; Hoo, R.L.C.; Sweeney, G.; Vanhoutte, P.M.; Wang, Y.; Wu, D.; Chu, W.; Qin, G.; Lam, K.S.L. Selective elevation of adiponectin production by the natural compounds derived from a medicinal herb alleviates insulin resistance and glucose intolerance in obese mice. Endocrinology 2009, 150, 625–633.
  24. Berg AH, Scherer PE (2005) Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96: 939–949.
  25. Moschen, A.R.; Wieser, V.; Tilg, H. Adiponectin: Key player in the adipose tissue-liver crosstalk. Curr. Med. Chem. 2012, 19, 5467–5473.
  26. Whitehead, J.P.; Richards, A.A.; Hickman, I.J.; Macdonald, G.A.; Prins, J.B. Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes. Metab. 2006, 8, 264–280.
  27. Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A. & Chen, H. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821-1830.
  28. Hotamisligil, G. S., Shargill, N. S. & Spiegelman, B. M. (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87-91.
  29. Jayaprakasam B., Olson L. K., Schutzki R. E., Tai M. H., Nair G. M. (2006): Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J. Agric. Food Chem. 54, 243-248.
  30. Ding S. Y., Shen Z. F., Chen Y.T., Sun S.J., Liu Q., Xie M. Z. (2005): Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Acta Pharmacologica. Sinica. 26, 575−580.
  31. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132(6):2169-80.
  32. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25(1):4-7.