Beneficial Effect of Lycopene on Diabetes Mellitus and its Possible Mechanism: A Review


  • Hanna Goenawan Physiology Division, Department of Biomedical Science, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
  • Yuni S. Pratiwi Physiology Division, Department of Biomedical Science, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
  • Nararian P. Dewi Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
  • Achadiyani Achadiyani Cell Biology Division, Department of Biomedical Science, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
  • Nova Sylviana Physiology Division, Department of Biomedical Science, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia


Lycopene, Diabetes, Oxidative stress, Inflammation, Apoptosis, Autophagy


Lycopene has received a lot of attention because of its benefits in various chronic diseases such as cancer, cardiovascular, neurodegenerative, and metabolic diseases such as diabetes. Various studies using cell culture, animals, and humans as subjects have proven the benefits of lycopene in diabetes, but none have yet explained its molecular mechanism in detail. Therefore, this study aims to summarize and describe the benefits of lycopene in diabetes mellitus and the potential underlying mechanisms. This study is a literature review that uses articles obtained from the PubMed and Google Scholar databases by entering the keywords lycopene, diabetes, oxidative stress, inflammation, apoptosis, and autophagy either separately or in combination to obtain a logical concept. There are 33 main articles summarized and discussed in this study. Lycopene shows potential use in the therapy and prevention of diabetes complications, particularly through its antioxidant and anti-inflammatory activities. Lycopene also increases insulin signaling activity via the PI3K/AKT pathway. Moreover, lycopene supplementation contributes to decrease apoptosis in brain cells and weakens apoptosis in podocytes through the autophagy process. Knowing these benefits, lycopene supplementation in diabetics needs to be considered, but further research is needed in the form of large clinical trials to prove the benefits of lycopene in diabetes and the optimal dosage required. 


International Diabetes Federation - Facts & figures [Internet]. [cited 2020 Nov 25]. Available from:

Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang YH, Stevens GA, Rao M, Ali MK, Riley LM, Robinson CA, Ezzati M. National, regional, and global trends in fasting plasma

glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet. 2011;378(9785):31-40.

Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol. 2019; 18(2):104-109.

Gupta A, Behl T, Sachdeva M. Key milestones in the diabetes research: A comprehensive update. Obes Med. 2020; 17:100183.

Yegin SÇ, Yur F, Ceylan E. Effect of lycopene application in rats with experimental diabetes using lipoprotein, paraoxonase and cytokines. J Membr Biol. 2013; 246(8):621-626.

Figueiredo ID, Lima TFO, Inácio MD, Costa MC, Assis RP, Brunetti IL, Baviera AM. Lycopene improves the metformin effects on glycemic control and decreases biomarkers of glycoxidative stress in diabetic rats. Diabetes, Metab Syndr Obes Targets Ther. 2020; 13:3117-3135.

Cahn A and Cefalu WT. Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care. 2016; 39(Suppl 2):S137-S145.

Akhter MS and Uppal P. Toxicity of Metformin and Hypoglycemic Therapies. Adv Chronic Kidney Dis. 2020; 27(1):18-30.

Prabhakar P, Kumar A, Doble M. Combination therapy: A new strategy to manage diabetes and its complications. Phytomed. 2014; 21(2):123-130.

Venkatakrishnan K, Chiu HF, Wang CK. Popular functional foods and herbs for the management of type-2-diabetes mellitus: A comprehensive review with special reference to clinical trials and its proposed mechanism. J Funct Foods. 2019; 57:425-438.

Ozmen O, Topsakal S, Haligur M, Aydogan A, Dincoglu D. Effects of caffeine and lycopene in experimentally induced diabetes mellitus. Pancreas. 2016; 45(4):579-583.

Ozmutlu S, Dede S, Ceylan E. The effect of lycopene treatment on ACE activity in rats with experimental diabetes. JRAAS - J Renin-Angiotensin-Aldosterone Syst. 2012; 13(3):328-333.

Eze ED, Afodun AM, Kasolo J, Kasozi KI. Lycopene improves on basic hematological and immunological

parameters in diabetes mellitus. BMC Res Notes. 2019; 12(1):1-6.

Cho KS, Shin M, Kim S, Lee SB. Recent advances in studies on the therapeutic potential of dietary carotenoids in neurodegenerative diseases. Oxid Med Cell Longev. 2018; 2018:1-13.

Böhm F, Edge R, Truscott TG. Interactions of dietary carotenoids with singlet oxygen (1O2) and free radicals: Potential effects for human health. Acta Biochim Pol. 2012; 59(1):27-30.

Zhu J, Wang CG, Xu YG. Lycopene attenuates endothelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress. Pharm Biol. 2011; 49(11):1144-1149.

Bayramoglu A, Bayramoglu G, Senturk H. Lycopene partially reverses symptoms of diabetes in rats with streptozotocin-induced diabetes. J Med Food. 2013; 16(2):128-132.

Ejike DE. Effect of Lycopene on Altered Kidney Antioxidant Enzymes Activity and Functions in Streptozotocin-Induced Diabetic Wistar Rats. Cell Biol. 2015; 3(1):1.

Eze E, Mohammed A, Tanko Y, Ahmed A, Rabiu K. Hypoglycaemic Effect of Lycopene in StreptozotocinInduced Diabetic Wistar Rats. Br J Med Med Res. 2015; 7(9):762-770.

Przybylska S. Lycopene – a bioactive carotenoid offering multiple health benefits: a review. J Food Sci Technol. 2019; 55(1):11-32.

Li N, Wu X, Zhuang W, Xia L, Chen Y, Wu C, Rao Z, Du L, Zhao R, Yi M, Wan Q, Zhou Y. Tomato and lycopene and multiple health outcomes: Umbrella review. Food Chem. 2021; 343:128396.

Zeng Y, Mu G, Huang S, Zeng X, Cheng H, Li Z. Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose.Nutr Res Pract. 2014; 8(4):368-376.

Badkook M, McCullough F, Ahmed N. Effect of a high monounsaturated fatty acid diet alone or with combined vitamin e and C, or lycopene intake on oxidative stress in patients with type 2 diabetes mellitus. Br J Diabetes Vasc Dis. 2012; 12(2):81-86.

Aydin M and Çelik S. Effects of lycopene on plasma glucose, insulin levels, oxidative stress, and body weights of streptozotocin-induced diabetic rats. Turkish J Med Sci. 2012; 42(SUPPL.2):1406-1413.

Ejike DE, Adam MA, Sheu OS, Nganda P, Iliya E, Moses DA, Alfred OO, Karimah MR. Lycopene attenuates diabetesinduced oxidative stress in Wistar rats. J Diabetes Endocrinol. 2018; 9(2):11-19.

Ejike DE and Yusuf T. Effects of Lycopene on Liver Markers and Glucokinase Activity in Experimentallyinduced Diabetes Mellitus Rat Model. J basic appl Res. 2016; 2(3):353-362.

Newsholme P, Cruzat VF, Keane KN, Carlessi R, De Bittencourt PIH. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016; 473(24):4527-4550.

Ighodaro OM. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomed Pharmacother. 2018; 108:656-662.

Karahan F, Dede S, Ceylan E. The Effect of Lycopene Treatment on Oxidative DNA Damage of Experimental Diabetic Rats. Open Clin Biochem J. 2018; 8(1):1-6.

Zheng Z, Yin Y, Lu R, Jiang Z. Lycopene Ameliorated Oxidative Stress and Inflammation in Type 2 Diabetic Rats. J Food Sci. 2019; 84(5):1194-1200.

Bigagli E and Lodovici M. Circulating oxidative stress biomarkers in clinical studies on type 2 diabetes and its complications. Oxid Med Cell Longev. 2019; 2019:1-17.

Hussein SA, Hassanein MR, Awadalla MA. Lycopene and its Potential Role in Diabetic Nephropathy Induced in Rats. Benha Vet Med J. 2018; 34(3):26-41.

Yin Y, Zheng Z, Jiang Z. Effects of lycopene on metabolism of glycolipid in type 2 diabetic rats. Biomed Pharmacother. 2019; 109(74):2070-2077.

Saracoğlu G, Baş H, Pandır D. Furan ‑ induced cardiotoxicity in diabetic rats and protective role of lycopene. J Food Biochem. 2019; 2018:1-9.

Singh K and BS B. Ameliorative Effect of Lycopene on Lipid Peroxidation and Certain Antioxidant Enzymes in Diabetic Patients. J Diabetes Metab. 2012; 03(06):202.

Li W, Wang G, Lu X, Jiang Y, Xu L, Zhao X. Lycopene ameliorates renal function in rats with streptozotocin-induced diabetes. Int J Clin Exp Pathol. 2014; 7(8):5008-5015.

Guo Y, Liu Y, Wang Y. Beneficial effect of lycopene on anti-diabetic nephropathy through diminishing inflammatory response and oxidative stress. Food Funct. 2015; 6(4):1150-1156.

Tabrez S, Al-Shali KZ, Ahmad S. Lycopene powers the inhibition of glycation-induced diabetic nephropathy: A novel approach to halt the AGE-RAGE axis menace. BioFactors. 2015; 41(5):372-381.

Uçar S and Pandir D. Furan induced ovarian damage in non ‑diabetic and diabetic rats and cellular protective role of lycopene. Arch Gynecol Obstet. 2017; 296(5):1027-1037.

Assis RP, Arcaro CA, Gutierres VO, Oliveira JO, Costa PI, Baviera AM, Brunetti IL. Combined effects of curcumin and lycopene or bixin in yoghurt on inhibition of LDL oxidation and increases in HDL and paraoxonase levels in streptozotocin-diabetic rats. Int J Mol Sci. 2017;18(4):332.

Belter A, Giel-Pietraszuk M, Oziewicz S, Chomczyński P, Barciszewski J. [Lycopene–occurrence, properties and applications]. [Likopen–wystepowanie, właściwości oraz potencjalne zastosowanie.]. Postepy Biochem. 2011; 57(4):372-380.

Nabavi SF, Barber AJ, Spagnuolo C, Russo GL, Daglia M, Nabavi SM, Eduardo Sobarzo-Sánchez. Nrf2 as molecular target for polyphenols: A novel therapeutic strategy in diabetic retinopathy. Crit Rev Clin Lab Sci. 2016; 53(5):293-312.

Pall ML, Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao. 2015; 67(1):1-18.

Kumar H, Kim IS, More SV, Kim BW, Choi DK. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep. 2014;31(1):109-139.

Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stressinduced insulin resistance in cardiac cells in vitro and in vivo. Diabetes. 2011; 60(2):625-633.

Bitar MS and Al-Mulla F. A defect in nrf2 signaling constitutes a mechanism for cellular stress hypersensitivity in a genetic rat model of type 2 diabetes. Am J Physiol -Endocrinol Metab. 2011; 301(6):1119-1129.

Siewert S, González I, Santillán L, Lucero R, Ojeda MS, Gimenez MS. Downregulation of Nrf2 and HO-1 expression contributes to oxidative stress in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina. J Diabetes Mellit. 2013; 3(2):71-78.

Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014; 105(2):141-150.

Zeng Z, He W, Jia Z, Hao S. Lycopene Improves Insulin Sensitivity through Inhibition of STAT3/Srebp-1c-Mediated Lipid Accumulation and Inflammation in Mice fed a HighFat Diet. Exp Clin Endocrinol Diabetes. 2017; 125(9):610-617.

Yin Q, Ma Y, Hong Y, Hou X, Chen J, Shen C, Sun M, Shang Y, Dong S, Zeng Z, Pei J, Liu X. Lycopene attenuates insulin signaling deficits, oxidative stress, neuroinflammation, and cognitive impairment in fructosedrinking insulin resistant rats. Neuropharmacology. 2014; 86:389-396.

Fukami K, Yamagishi SI, Coughlan MT, Harcourt BE, Kantharidis P, Thallas-Bonke V, Okuda S, Cooer ME, Forbes JM. Ramipril inhibits AGE-RAGE-induced matrix metalloproteinase-2 activation in experimental diabetic nephropathy. Diabetol Metab Syndr. 2014; 6:86.

Icel E, Icel A, Uçak T, Karakurt Y, Elpeze B, Keskin Çimen F, Süleyman H. The effects of lycopene on alloxan induced diabetic optic neuropathy. Cutan Ocul Toxicol. 2019; 38(1):88-92.

Didonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer. Immunol Rev. 2012; 246(1):379-400.

Abeyrathna P and Su Y. The critical role of Akt in cardiovascular function. Vascul Pharmacol. 2015; 74:38-48.

Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology. McGraw-Hill. 2018.

Bathina S and Das UN. Dysregulation of PI3K-Akt-mTOR pathway in brain of streptozotocin-induced type 2 diabetes mellitus in Wistar rats. Lipids Health Dis. 2018; 17:1-11.

Huang X, Liu G, Guo J, Su ZQ. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018;


Wang Q, Li RUI, Xiao ZHI, Hou CUN. Lycopene attenuates high glucose ‑ mediated apoptosis in MPC5 podocytes by promoting autophagy via the PI3K/AKT signaling pathway. Exp Ther Med. 2020; 20(3):2870-2878.

Demirtas L, Guclu A, Erdur FM, Akbas EM, Ozcicek A, Onk D, Turkmen K. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res. 2016;144(4):515-524.

Turkmen K. Inflammation, oxidative stress, apoptosis, and autophagy in diabetes mellitus and diabetic kidney disease: the Four Horsemen of the Apocalypse. Int Urol Nephrol. 2017; 49:837-844.

Liu W-H, Wang Q-N, Zhou Y, Wang Y-J, Tong Z. Divergent effects of lycopene on pancreatic alpha and beta cells. Sheng Li Xue Bao. 2020; 72(2):133-138.

Soleymaninejad M, Joursaraei SG, Feizi F, Jafari Anarkooli I. The Effects of Lycopene and Insulin on Histological Changes and the Expression Level of Bcl-2 Family Genes in the Hippocampus of Streptozotocin-Induced Diabetic Rats. J Diabetes Res. 2017; 2017:4650939.

Malekiyan R, Abdanipour A, Sohrabi D, Anarkooli IJ. Antioxidant and neuroprotective effects of lycopene and insulin in the hippocampus of streptozotocin-induced diabetic rats. Biomed Rep. 2019; 10(1):47-54.

Rahmeier FL, Zavalhia LS, Tortorelli LS, Huf F, Géa LP, Meurer RT, Machado AC, Gomez R, Fernandes MC. The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats. Neurosci Lett. 2016; 630:84-92.

Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and Cognitive Impairment. Curr Diab Rep. 2016;16(9):87.

Zeng YC, Peng LS, Zou L, Huang SF, Xie Y, Mu GP, Zeng XH, Zhou XL, Zeng YC. Protective effect and mechanism of lycopene on endothelial progenitor cells (EPCs) from type 2 diabetes mellitus rats. Biomed Pharmacother. 2017; 92:8694.




How to Cite

Goenawan, H., Pratiwi, Y. S., Dewi, N. P., Achadiyani, A., & Sylviana, N. (2021). Beneficial Effect of Lycopene on Diabetes Mellitus and its Possible Mechanism: A Review: Tropical Journal of Natural Product Research (TJNPR), 5(3), 420–433. Retrieved from