Skip to main content Accessibility help

Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation

  • Jintian He (a1), Yu Niu (a1), Fei Wang (a1), Chao Wang (a1), Tao Cui (a1), Kaiwen Bai (a1), Jingfei Zhang (a1), Xiang Zhong (a1), Lili Zhang (a1) and Tian Wang (a1)...


Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1β and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.


Corresponding author

*Corresponding author: T. Wang, fax +86 25 84396195, email


Hide All
1. De, OM, Blossner, M, Villar, J, et al. (1998) Levels and patterns of intrauterine growth retardation in developing countries. Eur J Nutr 52, Suppl. 1, S5S15.
2. Hay, WW, Thureen, PJ & Anderson, MS (2001) Intrauterine growth restriction. NeoReviews 2, e129e138.
3. Varvarigou, AA (2010) Intrauterine growth restriction as a potential risk factor for disease onset in adulthood. J Pediatr Endocrinol Metab 23, 215224.
4. Barker, DJ, Eriksson, JG, Forsen, T, et al. (2002) Fetal origins of adult disease: strength of effects and biological basis. Int J Endocrinol 31, 12351239.
5. Mcmillen, IC & Robinson, JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85, 571633.
6. Hales, CN & Barker, DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60, 520.
7. Junjun, W, Lixiang, C, Defa, L, et al. (2008) Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs. J Nutr 138, 6066.
8. Raghupathy, R, Al-Azemi, M & Azizieh, F (2012) Intrauterine growth restriction: cytokine profiles of trophoblast antigen-stimulated maternal lymphocytes. Clin Dev Immunol 2012, 734865.
9. Aggarwal, BB, Sundaram, C, Malani, N, et al. (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595, 175.
10. Miłobȩdzka, J, Kostanecki, Sv & Lampe, V (1910) Zur kenntnis des curcumins (Knowledge of curcumins). Eur J Inorg Chem 43, 21632170.
11. Ghorbani, Z, Hekmatdoost, A & Mirmiran, P (2014) Anti-hyperglycemic and insulin sensitizer effects of turmeric and its principle constituent curcumin. Int J Endocrinol Metab 12, e18081.
12. Wang, ME, Chen, YC, Chen, IS, et al. (2012) Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J Nutr Biochem 23, 13521366.
13. Somparn, P, Phisalaphong, C, Nakornchai, S, et al. (2007) Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm Bull 30, 7478.
14. Ruby, AJ, Kuttan, G, Babu, KD, et al. (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94, 7983.
15. Mazidi, M, Karimi, E, Meydani, M, et al. (2016) Curcumin. World J Methodol 6, 112117.
16. Zhang, J, Xu, L, Zhang, L, et al. (2014) Curcumin attenuates d-galactosamine/lipopolysaccharide-induced liver injury and mitochondrial dysfunction in mice. J Nutr 144, 12111218.
17. Molina-Jijon, E, Tapia, E, Zazueta, C, et al. (2011) Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway. Free Radic Biol Med 51, 15431557.
18. Kowluru, RA & Kanwar, M (2007) Effects of curcumin on retinal oxidative stress and inflammation in diabetes. Nutr Metab 4, 18.
19. Desai, M, Gayle, D, Babu, J, et al. (2005) Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition. Am J Physiol Regul Integr Comp Physiol 288, R91R96.
20. Widdowson, EM & McCance, RA (1975) A review: new thoughts on growth. Pediatr Res 9, 154156.
21. Reeves, PG, Nielsen, FH & Fahey, GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123, 19391951.
22. Toydemir, T, Kanter, M, Erboga, M, et al. (2015) Antioxidative, antiapoptotic, and proliferative effect of curcumin on liver regeneration after partial hepatectomy in rats. Toxicol Ind Health 31, 162172.
23. Caprau, DM, O’Grady, SP, Callaway, CW, et al. (2007) IUGR alters IGF1 receptor gene expression, DNA methylation and histones acetylation in the brain. Early Hum Dev 83, S47.
24. He, J, Dong, L, Xu, W, et al. (2015) Dietary tributyrin supplementation attenuates insulin resistance and abnormal lipid metabolism in suckling piglets with intrauterine growth retardation. PLOS ONE 10, e0136848.
25. Schmittgen, TD & Livak, KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3, 11011108.
26. Onis, MD, Blössner, M, Borghi, E, et al. (2004) Estimates of global prevalence of childhood underweight in 1990 and 2015. JAMA 291, 26002606.
27. Aiken, CE & Ozanne, SE (2013) Transgenerational developmental programming. Hum Reprod Update 20, 6375.
28. Tarryadkins, JL, Fernandeztwinn, DS, Hargreaves, IP, et al. (2015) Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth. Am J Clin Nutr 103, 579588.
29. Sahin, K, Orhan, C, Tuzcu, Z, et al. (2012) Curcumin ameloriates heat stress via inhibition of oxidative stress and modulation of Nrf2/HO-1 pathway in quail. Food Chem Toxicol 50, 40354041.
30. Zhang, JF, Hu, ZP, Lu, CH, et al. (2015) Dietary curcumin supplementation protects against heat-stress-impaired growth performance of broilers possibly through a mitochondrial pathway. J. Anim. Sci 93, 16561665.
31. He, JH, Xie, H & Wu, S (2016) Dietary supplementation of curcumin alleviates NF-κB-dependent skeletal muscle wasting in rat. Endocr Metab Immune Disord Drug Targets 16, 140147.
32. Starke, RM, Daniel, MS & Dumont, RMAS (2014) Tumor necrosis factor-α modulates cerebral aneurysm formation and rupture. Alcohol Clin Exp Res 5, 269277.
33. Deventer, SJHv (2000) Cytokine and cytokine receptor polymorphisms in infectious disease. Intensive Care Med 26, S98S102.
34. Liu, L, Shang, Y, Li, M, et al. (2015) Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway. Clin Exp Pharmacol Physiol 42, 520529.
35. Soetikno, V, Sari, FR, Veeraveedu, PT, et al. (2011) Curcumin ameliorates macrophage infiltration by inhibiting NF-κB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy. Nutr Metab 8, 35.
36. Kuo, PC, Li, K, Alfrey, EJ, et al. (1995) Magnetic resonance imaging and hepatic hemodynamics: correlation with metabolic function in liver transplantation candidates. Surgery 117, 373379.
37. Nyblom, H, Berggren, U, Balldin, J, et al. (2004) High ast/alt ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol 39, 336339.
38. Tang, Y, Chao, G, Xing, M, et al. (2012) Quercetin prevents ethanol-induced dyslipidemia and mitochondrial oxidative damage. Food Chem Toxicol 50, 11941200.
39. Liu, C, Lin, G, Wang, X, et al. (2013) Intrauterine growth restriction alters the hepatic proteome in fetal pigs. J Nutr Biochem 24, 954959.
40. Zhao, HL, Song, CH & Chai, OH (2012) Negative effects of curcumin on liver injury induced by alcohol. Phytother Res 26, 18571863.
41. Hiscott, J, Kwon, H & Genin, P (2001) Hostile takeovers: viral appropriation of the NF-kB pathway. J Clin Invest 107, 143151.
42. Echeverri, R, Nancy, P & Mockus, S (2008) Factor nuclear κB (NF-κB): signalosoma y su importancia en enfermedades inflamatorias y cancer (Nuclear factor κB (NF-κB): signalosome and its importance in inflammatory diseases and cancer). Rev Fac Med 56, 133146.
43. Chen, F, Castranova, V, Shi, X, et al. (1999) New insights into the role of nuclear factor-κB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45, 717.
44. Zhong, X, Li, W, Huang, X, et al. (2012) Effects of glutamine supplementation on the immune status in weaning piglets with intrauterine growth retardation. Arch Anim Nutr 66, 347356.
45. Yang, X, He, G, Hao, Y, et al. (2010) The role of the JAK2-STAT3 pathway in pro-inflammatory responses of EMF-stimulated N9 microglial cells. J Neuroinflammation 7, 54.
46. Surh, YJ, Chun, KS, Cha, HH, et al. (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480-481, 243268.
47. Kim, HY, Park, EJ, Joe, EH, et al. (2003) Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J Immunol 171, 60726079.
48. Reyes-Gordillo, K, Segovia, J, Shibayama, M, et al. (2007) Curcumin protects against acute liver damage in the rat by inhibiting NF-κB, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta 1770, 989996.
49. Centini, G, Kenanidis, A, Rosignoli, L, et al. (2004) Intrauterine oxidative stress and doppler flussimetry in fetuses with IUGR. Ultrasound Obstet Gynecol 24, 314.
50. Chaudhuri, AR, de Waal, EM, Pierce, A, et al. (2006) Detection of protein carbonyls in aging liver tissue: a fluorescence-based proteomic approach. Mech Ageing Dev 127, 849861.
51. Fang, YZ, Yang, S & Wu, G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18, 872879.
52. Mahmoud, KZ & Edens, FW (2003) Influence of selenium sources on age-related and mild heat stress-related changes of blood and liver glutathione redox cycle in broiler chickens (Gallus domesticus). Comp Biochem Physiol B Biochem Mol Biol 136, 921934.
53. Jones, DP (2002) Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 348, 93112.
54. Zhang, H, Chen, Y, Li, Y, et al. (2014) Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle. Br J Nutr 112, 876885.
55. Hracsko, Z, Orvos, H, Novak, Z, et al. (2013) Evaluation of oxidative stress markers in neonates with intra-uterine growth retardation. Redox Rep 13, 1116.
56. Wen, PL, Xue, TM, Yu, W, et al. (2015) Zn(II)-curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage. Environ Toxicol Pharmacol 39, 515524.
57. Suryanarayana, P, Satyanarayana, A, Balakrishna, N, et al. (2007) Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-induced diabetic rat. Med Sci Monit 13, BR286BR292.
58. Altıntoprak, N, Kar, M, Acar, M, et al. (2016) Antioxidant activities of curcumin in allergic rhinitis. Eur Arch Otorhinolaryngol 273, 37653773.
59. Gao, S, Duan, X, Wang, X, et al. (2013) Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 59, 739747.
60. Kensler, TW, Wakabayashi, N & Biswal, S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol 47, 89116.
61. Li, W & Kong, AN (2009) Molecular mechanisms of Nrf2-mediated antioxidant response. Mol Carcinog 48, 91104.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed