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Ellagic acid in suppressing in vivo and in vitro oxidative stresses

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Abstract

Oxidative stress is a biological condition produced by a variety of factors, causing several chronic diseases. Oxidative stress was, therefore, treated with natural antioxidants, such as ellagic acid (EA). EA has a major role in protecting against different diseases associated with oxidative stress. This review critically discussed the antioxidant role of EA in biological systems. The in vitro and in vivo studies have confirmed the protective role of EA in suppressing oxidative stress. The review also discussed the mechanism of EA in suppressing of oxidative stress, which showed that EA activates specific endogenous antioxidant enzymes and suppresses specific genes responsible for inflammation, diseases, or disturbance of biochemical systems. The amount of EA used and duration, which plays a significant role in the treatment of oxidative stress has been discussed. In conclusion, EA is a strong natural antioxidant, which possesses the suppressing power of oxidative stress in biological systems.

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References

  1. Zafrilla P, Ferreres F, Tomas-Barberan FA (2001) Effect of processing and storage on the antioxidant ellagic acid derivatives and flavonoids of red raspberry (Rubus idaeus) jams. J Agric Food Chem 49(8):3651–3655

    Article  CAS  Google Scholar 

  2. Barch DH, Rundhaugen LM, Stoner GD, Pillay NS, Rosche WA (1996) Structure-function relationships of the dietary anticarcinogen ellagic acid. Carcinogenesis 17(2):265–269

    Article  CAS  Google Scholar 

  3. Priyadarsini KI, Khopde SM, Kumar SS, Mohan H (2002) Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem 50(7):2200–2206

    Article  CAS  Google Scholar 

  4. Daniel EM, Krupnick AS, Heur Y-H, Blinzler JA, Nims RW, Stoner GD (1989) Extraction, stability, and quantitation of ellagic acid in various fruits and nuts. J Food Compos Anal 2(4):338–349

    Article  CAS  Google Scholar 

  5. Raudone L, Bobinaite R, Janulis V, Viskelis P, Trumbeckaite S (2014) Effects of raspberry fruit extracts and ellagic acid on respiratory burst in murine macrophages. Food Funct 5(6):1167–1174. https://doi.org/10.1039/c3fo60593k

    Article  CAS  PubMed  Google Scholar 

  6. Zeb A (2015) A reversed phase HPLC-DAD method for the determination of phenolic compounds in plant leaves. Anal Methods 7(18):7753–7757. https://doi.org/10.1039/C5AY01402F

    Article  CAS  Google Scholar 

  7. Landete JM (2011) Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int 44(5):1150–1160. https://doi.org/10.1016/j.foodres.2011.04.027

    Article  CAS  Google Scholar 

  8. Bobinaitė R, Viškelis P, Venskutonis PR (2012) Variation of total phenolics, anthocyanins, ellagic acid and radical scavenging capacity in various raspberry (Rubus spp.) cultivars. Food Chem 132(3):1495–1501. https://doi.org/10.1016/j.foodchem.2011.11.137

    Article  CAS  PubMed  Google Scholar 

  9. Bobinaitė R, Viskelis P, Bobinas Č, Mieželienė A, Alenčikienė G, Venskutonis PR (2016) Raspberry marc extracts increase antioxidative potential, ellagic acid, ellagitannin and anthocyanin concentrations in fruit purees. LWT - Food Sci Technol 66:460–467. https://doi.org/10.1016/j.lwt.2015.10.069

    Article  CAS  Google Scholar 

  10. Williams DJ, Edwards D, Pun S, Chaliha M, Sultanbawa Y (2014) Profiling ellagic acid content: the importance of form and ascorbic acid levels. Food Res Int 66:100–106. https://doi.org/10.1016/j.foodres.2014.09.003

    Article  CAS  Google Scholar 

  11. Liu Z, Chen Z, Han F, Kang X, Gu H, Yang L (2016) Microwave-assisted method for simultaneous hydrolysis and extraction in obtaining ellagic acid, gallic acid and essential oil from Eucalyptus globulus leaves using Brönsted acidic ionic liquid [HO3S(CH2)4mim]HSO4. Ind Crop Prod 81:152–161. https://doi.org/10.1016/j.indcrop.2015.11.074

    Article  CAS  Google Scholar 

  12. Karakurt S, Semiz A, Celik G, Gencler-Ozkan AM, Sen A, Adali O (2016) Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum. Nutr Cancer 68(1):173–183. https://doi.org/10.1080/01635581.2016.1115092

    Article  CAS  PubMed  Google Scholar 

  13. Sarabhai S, Harjai K, Sharma P, Capalash N (2015) Ellagic acid derivatives from Terminalia chebula Retz. increase the susceptibility of Pseudomonas aeruginosa to stress by inhibiting polyphosphate kinase. J Appl Microbiol 118(4):817–825. https://doi.org/10.1111/jam.12733

    Article  CAS  PubMed  Google Scholar 

  14. González-Sarrías A, García-Villalba R, Núñez-Sánchez M, Tomé-Carneiro J, Zafrilla P, Mulero J, Tomás-Barberán FA, Espín JC (2015) Identifying the limits for ellagic acid bioavailability: a crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts. J Funct Foods A 19:225–235. https://doi.org/10.1016/j.jff.2015.09.019

    Article  CAS  Google Scholar 

  15. Zahin M, Ahmad I, Gupta RC, Aqil F (2014) Punicalagin and ellagic acid demonstrate antimutagenic activity and inhibition of benzo[a]pyrene induced DNA adducts. Biomed Res Int 2014:467465. https://doi.org/10.1155/2014/467465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Selma MV, Romo-Vaquero M, Garcia-Villalba R, Gonzalez-Sarrias A, Tomas-Barberan FA, Espin JC (2016) The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism. Food Funct 7(4):1769–1774. https://doi.org/10.1039/c5fo01100k

    Article  CAS  PubMed  Google Scholar 

  17. Sun W, Yan C, Frost B, Wang X, Hou C, Zeng M, Gao H, Kang Y, Liu J (2016) Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Sci Rep 6:34246. https://doi.org/10.1038/srep34246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Arafat SY, Nayeem M, Jahan S, Karim Z, Reza HM, Hossain MH, Shohel M, Alam MA (2016) Ellagic acid rich Momordica charantia fruit pulp supplementation prevented oxidative stress, fibrosis and inflammation in liver of alloxan induced diabetic rats. Orient Pharm Exp Med 16(4):267–278. https://doi.org/10.1007/s13596-016-0242-x

    Article  CAS  Google Scholar 

  19. Vattem DA, Shetty K (2005) Biological functionality of ellagic acid: a review. J Food Biochem 29(3):234–266. https://doi.org/10.1111/j.1745-4514.2005.00031.x

    Article  CAS  Google Scholar 

  20. Ahmed T, Setzer WN, Nabavi SF, Orhan IE, Braidy N, Sobarzo-Sanchez E, Nabavi SM (2016) Insights into effects of ellagic acid on the nervous system: a mini review. Curr Pharm Des 22(10):1350–1360

    Article  CAS  Google Scholar 

  21. de Oliveira MR (2016) The effects of ellagic acid upon brain cells: a mechanistic view and future directions. Neurochem Res 41(6):1219–1228. https://doi.org/10.1007/s11064-016-1853-9

    Article  CAS  PubMed  Google Scholar 

  22. Bell C, Hawthorne S (2008) Ellagic acid, pomegranate and prostate cancer—a mini review. J Pharm Pharmacol 60(2):139–144. https://doi.org/10.1211/jpp.60.2.0001

    Article  CAS  PubMed  Google Scholar 

  23. Naiki-Ito A, Chewonarin T, Tang M, Pitchakarn P, Kuno T, Ogawa K, Asamoto M, Shirai T, Takahashi S (2015) Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis. Prostate 75(2):151–160. https://doi.org/10.1002/pros.22900

    Article  CAS  PubMed  Google Scholar 

  24. Espin JC, Larrosa M, Garcia-Conesa MT, Tomas-Barberan F (2013) Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evid Based Complement Alternat Med 2013:270418. https://doi.org/10.1155/2013/270418

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tomás-Barberan FA, Espín JC, García-Conesa MT (2009) Bioavailability and metabolism of ellagic acid and elagitannins. In: Quideau S (ed) Chemistry and biology of ellagitannins: an underestimated class of Bioactive plant polyphenols, vol 1. World Scientific Publishing Co. Pte. Ltd., Singapore, pp 273–297

    Chapter  Google Scholar 

  26. Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez MA, Selma MV, García-Conesa MT, Espín JC (2017) Urolithins, the rescue of “old” metabolites to understand a “new” concept: metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res 61(1):1500901. https://doi.org/10.1002/mnfr.201500901

    Article  CAS  Google Scholar 

  27. Sies H (1991) Oxidative stress: from basic research to clinical application. Am J Med 91(3C):31S–38S

    Google Scholar 

  28. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97:55–74. https://doi.org/10.1016/j.ejmech.2015.04.040

    Article  CAS  PubMed  Google Scholar 

  29. Zeb A (2015) Chemistry and liquid chromatography methods for the analyses of primary oxidation products of triacylglycerols. Free Radic Res 49(5):549–564. https://doi.org/10.3109/10715762.2015.1022540

    Article  CAS  PubMed  Google Scholar 

  30. Qasim M, Bukhari SA, Ghani MJ, Masoud MS, Huma T, Arshad M, Haque A, Ibrahim Z, Javed S, Rajoka MI (2016) Relationship of oxidative stress with elevated level of DNA damage and homocysteine in cardiovascular disease patients. Pak J Pharm Sci 29(6(Suppl)):2297–2302

    PubMed  Google Scholar 

  31. Kim H, Yun J, Kwon SM (2016) Therapeutic strategies for oxidative stress-related cardiovascular diseases: removal of excess reactive oxygen species in adult stem cells. Oxid Med Cell Longev 2016:2483163. https://doi.org/10.1155/2016/2483163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wu J, Xia S, Kalionis B, Wan W, Sun T (2014) The role of oxidative stress and inflammation in cardiovascular aging. Biomed Res Int 2014:615312. https://doi.org/10.1155/2014/615312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pillon Barcelos R, Freire Royes LF, Gonzalez-Gallego J, Bresciani G (2017) Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise. Free Radic Res 51(2):222–236. https://doi.org/10.1080/10715762.2017.1291942

    Article  CAS  PubMed  Google Scholar 

  34. Ivanov AV, Valuev-Elliston VT, Tyurina DA, Ivanova ON, Kochetkov SN, Bartosch B, Isaguliants MG (2017) Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget 8(3):3895–3932. https://doi.org/10.18632/oncotarget.13904

    Article  PubMed  Google Scholar 

  35. Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360(1):201–205. https://doi.org/10.1124/jpet.116.237503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Naziroglu M (2012) Molecular role of catalase on oxidative stress-induced Ca(2+) signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res 32(3):134–141. https://doi.org/10.3109/10799893.2012.672994

    Article  CAS  PubMed  Google Scholar 

  37. Kruk J, Aboul-Enein HY (2017) Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem 17(11):904–919. https://doi.org/10.2174/1389557517666170228115324

    Article  CAS  PubMed  Google Scholar 

  38. Forcados GE, James DB, Sallau AB, Muhammad A, Mabeta P (2017) Oxidative stress and carcinogenesis: potential of phytochemicals in breast cancer therapy. Nutr Cancer 69(3):365–374. https://doi.org/10.1080/01635581.2017.1267777

    Article  CAS  PubMed  Google Scholar 

  39. Marotta F, Kumari A, Catanzaro R, Solimene U, Jain S, Minelli E, Harada M (2012) A phytochemical approach to experimental metabolic syndrome-associated renal damage and oxidative stress. Rejuvenation Res 15(2):153–156. https://doi.org/10.1089/rej.2011.1266

    Article  PubMed  Google Scholar 

  40. Fujita Y, Komagoe K, Sasaki Y, Uehara I, Okuda T, Yoshida T (1987) Studies on inhibition-mechanism of autoxidation by tannins and flavonoids. 1. Inhibition-mechanism of tannins on Cu (II)-catalyzed autoxidation of ascorbic acid. Yakugaku Zasshi-J Pharmaceut Soc Japan 107(1):17–22

    Article  CAS  Google Scholar 

  41. Mazzone G, Toscano M, Russo N (2013) Density functional predictions of antioxidant activity and UV spectral features of nasutin A, isonasutin, ellagic acid, and one of its possible derivatives. J Agric Food Chem 61(40):9650–9657. https://doi.org/10.1021/jf403262k

    Article  CAS  PubMed  Google Scholar 

  42. Larrosa M, Garcia-Conesa MT, Espin JC, Tomas-Barberan FA (2010) Ellagitannins, ellagic acid and vascular health. Mol Asp Med 31(6):513–539. https://doi.org/10.1016/j.mam.2010.09.005

    Article  CAS  Google Scholar 

  43. Kilic I, Yesiloglu Y, Bayrak Y (2014) Spectroscopic studies on the antioxidant activity of ellagic acid. Spectrochim Acta A 130:447–452. https://doi.org/10.1016/j.saa.2014.04.052

    Article  CAS  Google Scholar 

  44. Pavlova EL, Zografov NN, Simeonova LS (2016) Comparative study on the antioxidant capacities of synthetic influenza inhibitors and ellagic acid in model systems. Biomed Pharmacother 83:755–762. https://doi.org/10.1016/j.biopha.2016.07.046

    Article  CAS  PubMed  Google Scholar 

  45. Barch DH, Rundhaugen LM (1994) Ellagic acid induces NAD(P)H:quinone reductase through activation of the antioxidant responsive element of the rat NAD(P)H:quinone reductase gene. Carcinogenesis 15(9):2065–2068

    Article  CAS  Google Scholar 

  46. Cozzi R, Ricordy R, Bartolini F, Ramadori L, Perticone P, De Salvia R (1995) Taurine and ellagic acid: two differently-acting natural antioxidants. Environ Mol Mutagen 26(3):248–254

    Article  CAS  Google Scholar 

  47. Meyer AS, Heinonen M, Frankel EN (1998) Antioxidant interactions of catechin, cyanidin, caffeic acid, quercetin, and ellagic acid on human LDL oxidation. Food Chem 61(1–2):71–75. https://doi.org/10.1016/S0308-8146(97)00100-3

    Article  CAS  Google Scholar 

  48. Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R (2001) Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res 21(6A):3903–3908

    CAS  PubMed  Google Scholar 

  49. Devipriya N, Sudheer AR, Menon VP (2007) Dose-response effect of ellagic acid on circulatory antioxidants and lipids during alcohol-induced toxicity in experimental rats. Fundam Clin Pharmacol 21(6):621–630. https://doi.org/10.1111/j.1472-8206.2007.00551.x

    Article  CAS  PubMed  Google Scholar 

  50. Murugan V, Mukherjee K, Maiti K, Mukherjee PK (2009) Enhanced oral bioavailability and antioxidant profile of ellagic acid by phospholipids. J Agric Food Chem 57(11):4559–4565. https://doi.org/10.1021/jf8037105

    Article  CAS  PubMed  Google Scholar 

  51. Ratnam DV, Chandraiah G, Meena AK, Ramarao P, Kumar MN (2009) The co-encapsulated antioxidant nanoparticles of ellagic acid and coenzyme Q10 ameliorates hyperlipidemia in high fat diet fed rats. J Nanosci Nanotechnol 9(11):6741–6746

    Article  CAS  Google Scholar 

  52. Kumar KN, Raja SB, Vidhya N, Devaraj SN (2012) Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats. J Agric Food Chem 60(14):3665–3672. https://doi.org/10.1021/jf204128z

    Article  CAS  PubMed  Google Scholar 

  53. Baluchnejadmojarad T, Rabiee N, Zabihnejad S, Roghani M (2017) Ellagic acid exerts protective effect in intrastriatal 6-hydroxydopamine rat model of Parkinson’s disease: possible involvement of ERbeta/Nrf2/HO-1 signaling. Brain Res 1662:23–30. https://doi.org/10.1016/j.brainres.2017.02.021

    Article  CAS  PubMed  Google Scholar 

  54. Ding Y, Zhang B, Zhou K, Chen M, Wang M, Jia Y, Song Y, Li Y, Wen A (2014) Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: role of Nrf2 activation. Int J Cardiol 175(3):508–514. https://doi.org/10.1016/j.ijcard.2014.06.045

    Article  PubMed  Google Scholar 

  55. Chatterjee A, Chatterjee S, Das S, Saha A, Chattopadhyay S, Bandyopadhyay SK (2012) Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation. Acta Biochim Biophys Sin (Shanghai) 44(7):565–576. https://doi.org/10.1093/abbs/gms034

    Article  CAS  Google Scholar 

  56. Anderson KC, Teuber SS (2010) Ellagic acid and polyphenolics present in walnut kernels inhibit in vitro human peripheral blood mononuclear cell proliferation and alter cytokine production. Ann N Y Acad Sci 1190:86–96. https://doi.org/10.1111/j.1749-6632.2009.05259.x

    Article  CAS  PubMed  Google Scholar 

  57. Ahad A, Ganai AA, Mujeeb M, Siddiqui WA (2014) Ellagic acid, an NF-kappaB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact 219(1):64–75. https://doi.org/10.1016/j.cbi.2014.05.011

    Article  CAS  PubMed  Google Scholar 

  58. Ho CC, Huang AC, Yu CS, Lien JC, Wu SH, Huang YP, Huang HY, Kuo JH, Liao WY, Yang JS, Chen PY, Chung JG (2014) Ellagic acid induces apoptosis in TSGH8301 human bladder cancer cells through the endoplasmic reticulum stress- and mitochondria-dependent signaling pathways. Environ Toxicol 29(11):1262–1274. https://doi.org/10.1002/tox.21857

    Article  CAS  PubMed  Google Scholar 

  59. Anitha P, Priyadarsini RV, Kavitha K, Thiyagarajan P, Nagini S (2013) Ellagic acid coordinately attenuates Wnt/beta-catenin and NF-kappaB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis. Eur J Nutr 52(1):75–84. https://doi.org/10.1007/s00394-011-0288-y

    Article  CAS  PubMed  Google Scholar 

  60. Akbar A (2017) In-vivo effects of ellagic acid against the toxicity of thermally oxidized lipids. University of Malakand, Lower Dir

    Google Scholar 

  61. Fedeli D, Berrettini M, Gabryelak T, Falcioni G (2004) The effect of some tannins on trout erythrocytes exposed to oxidative stress. Mutat Res Genet Toxicol Environ Mutagen 563(2):89–96. https://doi.org/10.1016/j.mrgentox.2004.06.008

    Article  CAS  Google Scholar 

  62. Han DH, Lee MJ, Kim JH (2006) Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res 26(5A):3601–3606

    CAS  PubMed  Google Scholar 

  63. Chen CH, Liu TZ, Chen CH, Wong CH, Chen CH, Lu FJ, Chen SC (2007) The efficacy of protective effects of tannic acid, gallic acid, ellagic acid, and propyl gallate against hydrogen peroxide-induced oxidative stress and DNA damages in IMR-90 cells. Mol Nutr Food Res 51(8):962–968. https://doi.org/10.1002/mnfr.200600230

    Article  CAS  PubMed  Google Scholar 

  64. Khanduja KL, Avti PK, Kumar S, Mittal N, Sohi KK, Pathak CM (2006) Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism. Biochim Biophys Acta 1760(2):283–289. https://doi.org/10.1016/j.bbagen.2005.12.017

    Article  CAS  PubMed  Google Scholar 

  65. Bhosle SM, Huilgol NG, Mishra KP (2005) Enhancement of radiation-induced oxidative stress and cytotoxicity in tumor cells by ellagic acid. Clin Chim Acta 359(1–2):89–100. https://doi.org/10.1016/j.cccn.2005.03.037

    Article  CAS  PubMed  Google Scholar 

  66. Singh K, Khanna AK, Visen PK, Chander R (1999) Protective effect of ellagic acid on t-butyl hydroperoxide induced lipid peroxidation in isolated rat hepatocytes. Indian J Exp Biol 37(9):939–940

    CAS  PubMed  Google Scholar 

  67. Pavlica S, Gebhardt R (2005) Protective effects of ellagic and chlorogenic acids against oxidative stress in PC12 cells. Free Radic Res 39(12):1377–1390. https://doi.org/10.1080/09670260500197660

    Article  CAS  PubMed  Google Scholar 

  68. Umesalma S, Nagendraprabhu P, Sudhandiran G (2015) Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells. Mol Cell Biochem 399(1–2):303–313. https://doi.org/10.1007/s11010-014-2257-2

    Article  CAS  PubMed  Google Scholar 

  69. Rong S, Hu X, Zhao S, Zhao Y, Xiao X, Bao W, Liu L (2017) Procyanidins extracted from the litchi pericarp ameliorate atherosclerosis in ApoE knockout mice: their effects on nitric oxide bioavailability and oxidative stress. Food Funct 8(11):4210–4216. https://doi.org/10.1039/C7FO00747G

    Article  CAS  PubMed  Google Scholar 

  70. Chang WC, Yu YM, Chiang SY, Tseng CY (2008) Ellagic acid suppresses oxidised low-density lipoprotein-induced aortic smooth muscle cell proliferation: studies on the activation of extracellular signal-regulated kinase 1/2 and proliferating cell nuclear antigen expression. Br J Nutr 99(4):709–714. https://doi.org/10.1017/S0007114507831734

    Article  CAS  PubMed  Google Scholar 

  71. Sudheer AR, Muthukumaran S, Devipriya N, Menon VP (2007) Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes against nicotine-induced cellular and DNA damage in vitro: with the comparison of N-acetylcysteine. Toxicology 230(1):11–21. https://doi.org/10.1016/j.tox.2006.10.010

    Article  CAS  PubMed  Google Scholar 

  72. Hwang JM, Cho JS, Kim TH, Lee YI (2010) Ellagic acid protects hepatocytes from damage by inhibiting mitochondrial production of reactive oxygen species. Biomed Pharmacother 64(4):264–270. https://doi.org/10.1016/j.biopha.2009.06.013

    Article  CAS  PubMed  Google Scholar 

  73. Ou HC, Lee WJ, Lee SD, Huang CY, Chiu TH, Tsai KL, Hsu WC, Sheu WH (2010) Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxicol Appl Pharmacol 248(2):134–143. https://doi.org/10.1016/j.taap.2010.07.025

    Article  CAS  PubMed  Google Scholar 

  74. Qiu Z, Zhou B, Jin L, Yu H, Liu L, Liu Y, Qin C, Xie S, Zhu F (2013) In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells. Food Chem Toxicol 59:428–437. https://doi.org/10.1016/j.fct.2013.06.025

    Article  CAS  PubMed  Google Scholar 

  75. Lee WJ, Ou HC, Hsu WC, Chou MM, Tseng JJ, Hsu SL, Tsai KL, Sheu WH (2010) Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and inflammation in human endothelial cells. J Vasc Surg 52(5):1290–1300. https://doi.org/10.1016/j.jvs.2010.04.085

    Article  PubMed  Google Scholar 

  76. BenSaad LA, Kim KH, Quah CC, Kim WR, Shahimi M (2017) Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC Complement Altern Med 17(1):47. https://doi.org/10.1186/s12906-017-1555-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hseu YC, Chou CW, Senthil Kumar KJ, Fu KT, Wang HM, Hsu LS, Kuo YH, Wu CR, Chen SC, Yang HL (2012) Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes. Food Chem Toxicol 50(5):1245–1255. https://doi.org/10.1016/j.fct.2012.02.020

    Article  CAS  PubMed  Google Scholar 

  78. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616. https://doi.org/10.1016/j.freeradbiomed.2010.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim YS, Zerin T, Song HY (2013) Antioxidant action of ellagic acid ameliorates paraquat-induced A549 cytotoxicity. Biol Pharm Bull 36(4):609–615

    Article  CAS  Google Scholar 

  80. Bhosle SM, Ahire VR, Henry MS, Thakur VS, Huilgol NG, Mishra KP (2010) Augmentation of radiation-induced apoptosis by ellagic acid. Cancer Invest 28(3):323–330. https://doi.org/10.3109/07357900902849616

    Article  CAS  PubMed  Google Scholar 

  81. Hayes JE, Stepanyan V, Allen P, O’Grady MN, O’Brien NM, Kerry JP (2009) The effect of lutein, sesamol, ellagic acid and olive leaf extract on lipid oxidation and oxymyoglobin oxidation in bovine and porcine muscle model systems. Meat Sci 83(2):201–208. https://doi.org/10.1016/j.meatsci.2009.04.019

    Article  CAS  PubMed  Google Scholar 

  82. Hayes JE, Stepanyan V, Allen P, O’Grady MN, Kerry JP (2010) Effect of lutein, sesamol, ellagic acid and olive leaf extract on the quality and shelf-life stability of packaged raw minced beef patties. Meat Sci 84(4):613–620. https://doi.org/10.1016/j.meatsci.2009.10.020

    Article  CAS  PubMed  Google Scholar 

  83. Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH (2010) Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 19(8):e182–e190. https://doi.org/10.1111/j.1600-0625.2009.01044.x

    Article  Google Scholar 

  84. Martinez-Useros J, Li W, Cabeza-Morales M, Garcia-Foncillas J (2017) Oxidative stress: a new target for pancreatic cancer prognosis and treatment. J Clin Med. https://doi.org/10.3390/jcm6030029

    Article  PubMed  PubMed Central  Google Scholar 

  85. Ma-On C, Sanpavat A, Whongsiri P, Suwannasin S, Hirankarn N, Tangkijvanich P, Boonla C (2017) Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression. Med Oncol 34(4):57. https://doi.org/10.1007/s12032-017-0914-5

    Article  CAS  PubMed  Google Scholar 

  86. Mertens-Talcott SU, Bomser JA, Romero C, Talcott ST, Percival SS (2005) Ellagic acid potentiates the effect of quercetin on p21waf1/cip1, p53, and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitro. J Nutr 135(3):609–614

    Article  CAS  Google Scholar 

  87. Yang C-S, Tzou B-C, Liu Y-P, Tsai M-J, Shyue S-K, Tzeng S-F (2008) Inhibition of cadmium-induced oxidative injury in rat primary astrocytes by the addition of antioxidants and the reduction of intracellular calcium. J Cell Biochem 103(3):825–834. https://doi.org/10.1002/jcb.21452

    Article  CAS  PubMed  Google Scholar 

  88. Hassoun EA, Walter AC, Alsharif NZ, Stohs SJ (1997) Modulation of TCDD-induced fetotoxicity and oxidative stress in embryonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid. Toxicology 124(1):27–37

    Article  CAS  Google Scholar 

  89. Hassoun EA, Vodhanel J, Abushaban A (2004) The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure. J Biochem Mol Toxicol 18(4):196–203. https://doi.org/10.1002/jbt.20030

    Article  CAS  PubMed  Google Scholar 

  90. Vijayapadma V, Kalai Selvi P, Sravani S (2014) Protective effect of ellagic acid against TCDD-induced renal oxidative stress: modulation of CYP1A1 activity and antioxidant defense mechanisms. Mol Biol Rep 41(7):4223–4232. https://doi.org/10.1007/s11033-014-3292-5

    Article  CAS  Google Scholar 

  91. Ceribasi AO, Sakin F, Turk G, Sonmez M, Atessahin A (2012) Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages. Exp Toxicol Pathol 64(7–8):717–724. https://doi.org/10.1016/j.etp.2011.01.006

    Article  CAS  PubMed  Google Scholar 

  92. Atessahin A, Ceribasi AO, Yuce A, Bulmus O, Cikim G (2006) Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol 100(2):121–126. https://doi.org/10.1111/j.1742-7843.2006.00015.x

    Article  CAS  Google Scholar 

  93. Rehman MU, Tahir M, Ali F, Qamar W, Lateef A, Khan R, Quaiyoom A, Oday OH, Sultana S (2012) Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of ellagic acid. Mol Cell Biochem 365(1–2):119–127. https://doi.org/10.1007/s11010-012-1250-x

    Article  CAS  PubMed  Google Scholar 

  94. Sonaje K, Italia JL, Sharma G, Bhardwaj V, Tikoo K, Kumar MN (2007) Development of biodegradable nanoparticles for oral delivery of ellagic acid and evaluation of their antioxidant efficacy against cyclosporine A-induced nephrotoxicity in rats. Pharm Res 24(5):899–908. https://doi.org/10.1007/s11095-006-9207-y

    Article  CAS  PubMed  Google Scholar 

  95. Turk G, Ceribasi AO, Sahna E, Atessahin A (2011) Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin. Phytomedicine 18(5):356–361. https://doi.org/10.1016/j.phymed.2010.07.008

    Article  CAS  PubMed  Google Scholar 

  96. Yuce A, Atessahin A, Ceribasi AO, Aksakal M (2007) Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 101(5):345–349. https://doi.org/10.1111/j.1742-7843.2007.00129.x

    Article  CAS  PubMed  Google Scholar 

  97. Chao PC, Hsu CC, Yin MC (2009) Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice. Nutr Metab 6:33. https://doi.org/10.1186/1743-7075-6-33

    Article  CAS  Google Scholar 

  98. Turk G, Sonmez M, Ceribasi AO, Yuce A, Atessahin A (2010) Attenuation of cyclosporine A-induced testicular and spermatozoal damages associated with oxidative stress by ellagic acid. Int Immunopharmacol 10(2):177–182. https://doi.org/10.1016/j.intimp.2009.10.013

    Article  CAS  PubMed  Google Scholar 

  99. Pari L, Sivasankari R (2008) Effect of ellagic acid on cyclosporine A-induced oxidative damage in the liver of rats. Fundam Clin Pharmacol 22(4):395–401. https://doi.org/10.1111/j.1472-8206.2008.00609.x

    Article  CAS  PubMed  Google Scholar 

  100. Girish C, Pradhan SC (2012) Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice. J Pharmacol Pharmacother 3(2):149–155. https://doi.org/10.4103/0976-500X.95515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Uzar E, Alp H, Cevik MU, Firat U, Evliyaoglu O, Tufek A, Altun Y (2012) Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci 33(3):567–574. https://doi.org/10.1007/s10072-011-0775-1

    Article  PubMed  Google Scholar 

  102. Aiyer HS, Srinivasan C, Gupta RC (2008) Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats. Nutr Cancer 60(2):227–234. https://doi.org/10.1080/01635580701624712

    Article  PubMed  Google Scholar 

  103. Lin MC, Yin MC (2013) Preventive effects of ellagic acid against doxorubicin-induced cardio-toxicity in mice. Cardiovasc Toxicol 13(3):185–193. https://doi.org/10.1007/s12012-013-9197-z

    Article  CAS  PubMed  Google Scholar 

  104. Ayhanci A, Cengiz M, Mehtap Kutlu H, Vejselova D (2016) Protective effects of ellagic acid in D-galactosamine-induced kidney damage in rats. Cytotechnology 68(5):1763–1770. https://doi.org/10.1007/s10616-015-9928-z

    Article  CAS  PubMed  Google Scholar 

  105. Sakthivel M, Elanchezhian R, Ramesh E, Isai M, Jesudasan CN, Thomas PA, Geraldine P (2008) Prevention of selenite-induced cataractogenesis in Wistar rats by the polyphenol, ellagic acid. Exp Eye Res 86(2):251–259. https://doi.org/10.1016/j.exer.2007.10.016

    Article  CAS  PubMed  Google Scholar 

  106. Ahmed S, Rahman A, Saleem M, Athar M, Sultana S (1999) Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. Hum Exp Toxicol 18(11):691–698. https://doi.org/10.1191/096032799678839563

    Article  CAS  PubMed  Google Scholar 

  107. Ogawa Y, Kanatsu K, Iino T, Kato S, Jeong YI, Shibata N, Takada K, Takeuchi K (2002) Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats. Life Sci 71(7):827–839

    Article  CAS  Google Scholar 

  108. Kiasalari Z, Heydarifard R, Khalili M, Afshin-Majd S, Baluchnejadmojarad T, Zahedi E, Sanaierad A, Roghani M (2017) Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: an exploration of underlying mechanisms. Psychopharmacology 234(12):1841–1852. https://doi.org/10.1007/s00213-017-4589-6

    Article  CAS  PubMed  Google Scholar 

  109. Iino T, Nakahara K, Miki W, Kiso Y, Ogawa Y, Kato S, Takeuchi K (2001) Less damaging effect of whisky in rat stomachs in comparison with pure ethanol. Role of ellagic acid, the nonalcoholic component. Digestion 64(4):214–221. https://doi.org/10.1159/000048864

    Article  CAS  PubMed  Google Scholar 

  110. El-Shitany NA, El-Bastawissy EA, El-desoky K (2014) Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of interleukin-10 via an antioxidant mechanism. Int Immunopharmacol 19(2):290–299. https://doi.org/10.1016/j.intimp.2014.02.004

    Article  CAS  PubMed  Google Scholar 

  111. Umesalma S, Sudhandiran G (2010) Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 107(2):650–655. https://doi.org/10.1111/j.1742-7843.2010.00565.x

    Article  CAS  PubMed  Google Scholar 

  112. Mishra S, Vinayak M (2014) Ellagic acid induces novel and atypical PKC isoforms and promotes caspase-3 dependent apoptosis by blocking energy metabolism. Nutr Cancer 66(4):675–681. https://doi.org/10.1080/01635581.2013.878735

    Article  CAS  PubMed  Google Scholar 

  113. Kannan MM, Quine SD, Sangeetha T (2012) Protective efficacy of ellagic acid on glycoproteins, hematological parameters, biochemical changes, and electrolytes in myocardial infarcted rats. J Biochem Mol Toxicol 26(7):270–275. https://doi.org/10.1002/jbt.21418

    Article  CAS  PubMed  Google Scholar 

  114. Mishra S, Vinayak M (2015) Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice. BMC Complement Altern Med 15:281. https://doi.org/10.1186/s12906-015-0810-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Mishra S, Vinayak M (2011) Anti-carcinogenic action of ellagic acid mediated via modulation of oxidative stress regulated genes in Dalton lymphoma bearing mice. Leuk Lymphoma 52(11):2155–2161. https://doi.org/10.3109/10428194.2011.591014

    Article  CAS  PubMed  Google Scholar 

  116. Zeb A, Ullah S (2015) Sea buckthorn seed oil protects against the oxidative stress produced by thermally oxidized lipids. Food Chem 186(1):6–12. https://doi.org/10.1016/j.foodchem.2015.03.053

    Article  CAS  PubMed  Google Scholar 

  117. Yu YM, Chang WC, Wu CH, Chiang SY (2005) Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J Nutr Biochem 16(11):675–681. https://doi.org/10.1016/j.jnutbio.2005.03.013

    Article  CAS  PubMed  Google Scholar 

  118. Suzuki N, Masamune A, Kikuta K, Watanabe T, Satoh K, Shimosegawa T (2009) Ellagic acid inhibits pancreatic fibrosis in male Wistar Bonn/Kobori rats. Dig Dis Sci 54(4):802–810. https://doi.org/10.1007/s10620-008-0423-7

    Article  CAS  PubMed  Google Scholar 

  119. Makino-Wakagi Y, Yoshimura Y, Uzawa Y, Zaima N, Moriyama T, Kawamura Y (2012) Ellagic acid in pomegranate suppresses resistin secretion by a novel regulatory mechanism involving the degradation of intracellular resistin protein in adipocytes. Biochem Biophys Res Commun 417(2):880–885. https://doi.org/10.1016/j.bbrc.2011.12.067

    Article  CAS  PubMed  Google Scholar 

  120. Mishra S, Vinayak M (2013) Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway. Mol Biol Rep 40(2):1417–1428. https://doi.org/10.1007/s11033-012-2185-8

    Article  CAS  PubMed  Google Scholar 

  121. Majid S, Khanduja KL, Gandhi RK, Kapur S, Sharma RR (1991) Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice. Biochem Pharmacol 42(7):1441–1445

    Article  CAS  Google Scholar 

  122. Zeb A, Muhammad B, Ullah F (2017) Characterization of sesame (Sesamum indicum L.) seed oil from Pakistan for phenolic composition, quality characteristics and potential beneficial properties. J Food Meas Charact 11(3):1362–1369. https://doi.org/10.1007/s11694-017-9514-5

    Article  Google Scholar 

  123. Aranaz P, Romo-Hualde A, Zabala M, Navarro-Herrera D, Ruiz de Galarreta M, Gil AG, Martinez JA, Milagro FI, Gonzalez-Navarro CJ (2017) Freeze-dried strawberry and blueberry attenuates diet-induced obesity and insulin resistance in rats by inhibiting adipogenesis and lipogenesis. Food Funct 8(11):3999–4013. https://doi.org/10.1039/C7FO00996H

    Article  CAS  PubMed  Google Scholar 

  124. Zhang HM, Zhao L, Li H, Xu H, Chen WW, Tao L (2014) Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol Med 11(2):92–100. https://doi.org/10.7497/j.issn.2095-3941.2014.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Garcia-Nino WR, Zazueta C (2015) Ellagic acid: pharmacological activities and molecular mechanisms involved in liver protection. Pharmacol Res 97:84–103. https://doi.org/10.1016/j.phrs.2015.04.008

    Article  CAS  PubMed  Google Scholar 

  126. Stoner GD, Sardo C, Apseloff G, Mullet D, Wargo W, Pound V, Singh A, Sanders J, Aziz R, Casto B, Sun X (2005) Pharmacokinetics of anthocyanins and ellagic acid in healthy volunteers fed freeze-dried black raspberries daily for 7 days. J Clin Pharmacol 45(10):1153–1164. https://doi.org/10.1177/0091270005279636

    Article  CAS  PubMed  Google Scholar 

  127. Morillas-Ruiz J, Zafrilla P, Almar M, Cuevas MJ, López FJ, Abellán P, Villegas JA, González-Gallego J (2005) The effects of an antioxidant-supplemented beverage on exercise-induced oxidative stress: results from a placebo-controlled double-blind study in cyclists. Eur J Appl Physiol 95(5):543–549. https://doi.org/10.1007/s00421-005-0017-4

    Article  CAS  PubMed  Google Scholar 

  128. Morillas-Ruiz JM, Villegas García JA, López FJ, Vidal-Guevara ML, Zafrilla P (2006) Effects of polyphenolic antioxidants on exercise-induced oxidative stress. Clin Nutr 25(3):444–453. https://doi.org/10.1016/j.clnu.2005.11.007

    Article  CAS  PubMed  Google Scholar 

  129. Hayeshi R, Mutingwende I, Mavengere W, Masiyanise V, Mukanganyama S (2007) The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food Chem Toxicol 45(2):286–295. https://doi.org/10.1016/j.fct.2006.07.027

    Article  CAS  PubMed  Google Scholar 

  130. Chen B, Tuuli MG, Longtine MS, Shin JS, Lawrence R, Inder T, Michael Nelson D (2012) Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts. Am J Physiol Endocrinol Metab 302(9):E1142–E1152. https://doi.org/10.1152/ajpendo.00003.2012

    Article  CAS  Google Scholar 

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The author is grateful for financial assistance from the Higher Education Commission (HEC) Pakistan under NRPU Project No. 2344.

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  1. Laboratory of Biochemistry, Department of Biotechnology, University of Malakand, Chakdara, Lower Dir, Khyber Pakhtunkhwa, Pakistan

    Alam Zeb

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Zeb, A. Ellagic acid in suppressing in vivo and in vitro oxidative stresses. Mol Cell Biochem 448, 27–41 (2018). https://doi.org/10.1007/s11010-018-3310-3

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