Metabolic Brain Disease

, Volume 33, Issue 3, pp 705–711 | Cite as

Zeaxanthin improved diabetes-induced anxiety and depression through inhibiting inflammation in hippocampus

  • Xiaoyan Zhou
  • Tian Gan
  • Gaoxia Fang
  • Shangshang Wang
  • Yizhen Mao
  • Changjiang Ying
Original Article


It is generally accepted that inflammation plays a key role in anxiety and depression induced by diabetes. However, the underlying mechanism and effective treatment method of these diabetes-associated behavior disorders remain to be determined. In the present study, we attempted to illuminate the implication of zeaxanthin in anxiety, depression and neuroinflammation caused by hyperglycemia, and further elaborate the relevant mechanism under these neuropsychiatric disorders. In the current work, diabetic rats were induced by high glucose and fat diet followed by a single intraperitoneal injection of streptozocin, and zeaxanthin was orally administration every day (From 6th to 19th week). Diabetes-associated anxiety and depression were assessed using open field test (OFT) and Forced swimming test (FST) respectively. Moreover, the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in hippocampus were tested using ELISA and WB. Data showed that long-term zeaxanthin treatment improve diabetic symptoms and alleviate anxiety and depression in diabetic rats. Furthermore, excessive production of IL-6, IL-1β and TNF-α could be reduced with zeaxanthin treatment. In conclusion, we suggested that zeaxanthin can ameliorate diabetes-associated anxiety and depression, inhibit inflammation in diabetic rats. Our results could provide a potential therapeutic approach for the treatment of abnormal behavior induced by hyperglycemia.


Zeaxanthin Diabetes Anxiety Depression Inflammation 



This work was supported by a grant from the National Natural Science Foundation of China (81701298) and the Department of Science & Technology, Xuzhou, Jiangsu, China (No. KC14SH094).

Compliance with ethical standards

Conflict of interest

All authors state that there is no conflict of interest.


  1. Aswar U, Chepurwar S, Shintre S, Aswar M (2017) Telmisartan attenuates diabetes induced depression in rats. Pharmacol Rep 69(2):358–364CrossRefPubMedGoogle Scholar
  2. Black CN, Penninx BW, Bot M, Odegaard AO, Gross MD, Matthews KA et al (2016) Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study. Transl Psychiatry 6:e743CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bocco BM, Werneck-de-Castro JP, Oliveira KC, Fernandes GW, Fonseca TL, Nascimento BP et al (2016) Type 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like Behavior in Male Mice. Endocrinology 157(9):3682–3695CrossRefPubMedPubMedCentralGoogle Scholar
  4. Doyle T, Halaris A, Rao M (2014) Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings. Curr Diab Rep 14(2):560CrossRefPubMedGoogle Scholar
  5. Johari N, Manaf ZA, Ibrahim N, Shahar S, Mustafa N (2016) Predictors of quality of life among hospitalized geriatric patients with diabetes mellitus upon discharge. Clin Interv Aging 11:1455–1461CrossRefPubMedPubMedCentralGoogle Scholar
  6. Johnson EJ (2014) Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr Rev 72(9):605–612CrossRefPubMedGoogle Scholar
  7. Kou L, Du M, Zhang C, Dai Z, Li X, Zhang B (2017) The Hypoglycemic, Hypolipidemic, and Anti-Diabetic Nephritic Activities of Zeaxanthin in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats. Appl Biochem Biotechnol 182(3):944–955CrossRefPubMedGoogle Scholar
  8. Kowluru RA, Zhong Q, Santos JM, Thandampallayam M, Putt D, Gierhart DL (2014) Beneficial effects of the nutritional supplements on the development of diabetic retinopathy. Nutr Metab (Lond) 11(1):8CrossRefGoogle Scholar
  9. Laake JP, Stahl D, Amiel SA, Petrak F, Sherwood RA, Pickup JC et al (2014) The association between depressive symptoms and systemic inflammation in people with type 2 diabetes: findings from the South London Diabetes Study. Diabetes Care 37(8):2186–2192CrossRefPubMedGoogle Scholar
  10. Masís-Calvo M, Sequeira-Cordero A, Mora-Gallegos A, Fornaguera-Trías J (2013) Behavioral and neurochemical characterization of maternal care effects on juvenile Sprague-Dawley rats. Physiol Behav 118:212–217CrossRefPubMedGoogle Scholar
  11. Neelam K, Goenadi CJ, Lun K, Yip CC, Au Eong KG (2017) Putative protective role of lutein and zeaxanthin in diabetic retinopathy. Br J Ophthalmol 101(5):551–558CrossRefPubMedGoogle Scholar
  12. Patel SS, Udayabanu M (2014) Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice. Metab Brain Dis 29(1):121–130CrossRefPubMedGoogle Scholar
  13. da Silva Dias IC, Carabelli B, Ishii DK, de Morais H, de Carvalho MC (2016) Rizzo de Souza LE, et al. Indoleamine-2,3-Dioxygenase/Kynurenine Pathway as a Potential Pharmacological Target to Treat Depression Associated with Diabetes. Mol Neurobiol 53(10):6997–7009CrossRefPubMedGoogle Scholar
  14. Sluijs I, Cadier E, Beulens JW (2015) van der A DL, Spijkerman AM, van der Schouw YT. Dietary intake of carotenoids and risk of type 2 diabetes. Nutr Metab Cardiovasc Dis 25(4):376–381CrossRefPubMedGoogle Scholar
  15. Song X, Liu B, Cui L, Zhou B, Liu W, Xu F (2017a) Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiol Behav 179:487–493CrossRefPubMedGoogle Scholar
  16. Song Y, Zhang F, Ying C, Kumar KA, Zhou X (2017b) Inhibition of NF-κB activity by aminoguanidine alleviates neuroinflammation induced by hyperglycemia. Metab Brain Dis 32(5):1627–1637CrossRefPubMedGoogle Scholar
  17. Stringham NT, Holmes PV, Stringham JM (2017) Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults. Nutr Neurosci 15:1–11Google Scholar
  18. Vishwanathan R, Schalch W, Johnson EJ (2016) Macular pigment carotenoids in the retina and occipital cortex are related in humans. Nutr Neurosci 19(3):95–101CrossRefPubMedGoogle Scholar
  19. Wang J, Duan P, Cui Y, Li Q, Shi Y (2016) Geniposide alleviates depression-like behavior via enhancing BDNF expression in hippocampus of streptozotocin-evoked mice. Metab Brain Dis 31(5):1113–1122CrossRefPubMedGoogle Scholar
  20. Wayhs CA, Mescka CP, Vanzin CS, Ribas GS, Guerreiro G, Nin MS et al (2013) Brain effect of insulin and clonazepam in diabetic rats under depressive-like behavior. Metab Brain Dis 28(4):563–570CrossRefPubMedGoogle Scholar
  21. Wu B, Wei Y, Wang Y, Su T, Zhou L, Liu Y et al (2015) Gavage of D-Ribose induces Aβ-like deposits, Tau hyperphosphorylation as well as memory loss and anxiety-like behavior in mice. Oncotarget 6(33):34128–34142CrossRefPubMedPubMedCentralGoogle Scholar
  22. Xiao J, Wang J, Xing F, Han T, Jiao R, Liong EC et al (2014) Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway. PLoS One 9(4):e95214CrossRefPubMedPubMedCentralGoogle Scholar
  23. Ying C, Zhang F, Zhou X, Hu X, Chen J, Wen X et al (2015) Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus. Cell Mol Neurobiol 35(7):1027–1037CrossRefPubMedGoogle Scholar
  24. Ying C, Chen L, Wang S, Mao Y, Ling H, Li W et al (2017) Zeaxanthin ameliorates high glucose-induced mesangial cell apoptosis through inhibiting oxidative stress via activating AKT signalling-pathway. Biomed Pharmacother 90:796–805CrossRefPubMedGoogle Scholar
  25. Zhou X, Zhang F, Hu X, Chen J, Tang R, Zheng K et al (2017a) Depression can be prevented by astaxanthin through inhibition of hippocampal inflammation in diabetic mice. Brain Res 1657:262–268CrossRefPubMedGoogle Scholar
  26. Zhou X, Wang S, Ding X, Qin L, Mao Y, Chen L et al (2017b) Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/AKT signaling pathway. Brain Res Bull 132:190–198CrossRefPubMedGoogle Scholar
  27. Zhou X, Zhang F, Ying C, Chen J, Chen L, Dong J et al (2017c) Inhibition of iNOS alleviates cognitive deficits and depression in diabetic mice through downregulating the NO/sGC/cGMP/PKG signal pathway. Behav Brain Res 322(Pt A):70–82CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Xiaoyan Zhou
    • 1
  • Tian Gan
    • 2
  • Gaoxia Fang
    • 2
  • Shangshang Wang
    • 2
  • Yizhen Mao
    • 2
  • Changjiang Ying
    • 3
  1. 1.Laboratory of MorphologyXuzhou Medical UniversityXuzhouPeople’s Republic of China
  2. 2.The Graduate SchoolXuzhou Medical UniversityXuzhouPeople’s Republic of China
  3. 3.Department of EndocrinologyAffiliated Hospital of Xuzhou Medical UniversityXuzhouPeople’s Republic of China

Personalised recommendations