Pomegranate (Punica granatum L.) is a fruit rich in bioactive compounds with various biological properties that help maintain good health. In particular, the polyphenolic compounds punicalagin, ellagic acid, urolithins and gallic acid are among the main molecules with antioxidant potential identified in this fruit; that is, these compounds have the ability to prevent cellular alterations caused by oxidative stress and/or induce the body’s own antioxidant response to protect cells. As a result, numerous scientific studies have emerged in the last decade, focused on recognizing the pharmacological properties of these molecules, to prevent the development and progression of diseases in which oxidative stress plays a fundamental role. The objectives of this review are: 1) to point out the importance of antioxidants obtained from the diet and in particular those obtained from pomegranate, 2) to highlight the beneficial effects of ellagitannins, ellagic acid, urolithins and gallic acid against various pathologies, and 3) recognize that despite their potential as therapeutic agents, further research in humans is required to promote their use in the clinic.
Resúmen
La granada (Punica granatum L.) es una fruta rica en compuestos bioactivos con diversas propiedades biológicas que ayudan a mantener un buen estado de salud. Particularmente, los compuestos polifenólicos punicalagina, el ácido elágico, las urolitinas y el ácido gálico se encuentran entre las principales moléculas con potencial antioxidante identificadas en esta fruta; es decir, estos compuestos tienen la capacidad de prevenir las alteraciones celulares ocasionadas por el estrés oxidante y/o inducir la respuesta antioxidante del propio organismo para proteger a las células. A raíz de ello, numerosos estudios científicos han surgido en la última década, enfocados en reconocer las propiedades farmacológicas de estas moléculas, para evitar el desarrollo y la progresión de enfermedades en las que el estrés oxidante juega un papel fundamental. Los objetivos de esta revisión son: 1) señalar la importancia de los antioxidantes obtenidos de la dieta y en particular los obtenidos de la granada, 2) resaltar los efectos benéficos de los elagitaninos, el ácido elágico, las urolitinas y el ácido gálico contra diversas patologías, y 3) reconocer que a pesar de su potencial como agentes terapéuticos, se requiere investigación adicional en humanos para promover su uso en la clínica.
Ene | Feb | Mar | Abr | May | Jun | Jul | Ago | Sept | Oct | Nov | Dic |
---|---|---|---|---|---|---|---|---|---|---|---|
- | - | - | - | - | - | - | - | 7 | 22 | 20 | 26 |
Ene | Feb | Mar | Abr | May | Jun | Jul | Ago | Sept | Oct | Nov | Dic |
---|---|---|---|---|---|---|---|---|---|---|---|
10 | 12 | 14 | 5 | 8 | 11 | 5 | 12 | 22 | 28 | 49 | 13 |
Ene | Feb | Mar | Abr | May | Jun | Jul | Ago | Sept | Oct | Nov | Dic |
---|---|---|---|---|---|---|---|---|---|---|---|
16 | 28 | 16 | 26 | 14 | - | - | - | - | - | - | - |
Abdel-Moneim, A., El-Twab, S. M. A., Yousef, A. I., Reheim, E. S. A., & Ashour, M. B. (2018). Modulation of hyperglycemia and dyslipidemia in experimental type 2 diabetes by gallic acid and p-coumaric acid: The role of adipocytokines and PPARgamma. Biomed Pharmacother, 105, 1091-1097. DOI:10.1016/j.biopha.2018.06.096
Ahad, A., Ahsan, H., Mujeeb, M., & Siddiqui, W. A. (2015). Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells. Chem Biol Interact, 240, 292-303. DOI: 10.1016/j.cbi.2015.08.026
Ahad, A., Ganai, A. A., Mujeeb, M., & Siddiqui, W. A. (2014). Ellagic acid, an NF-kappaB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact, 219, 64-75. DOI:10.1016/j.cbi.2014.05.011
Ahmad, S., Alouffi, S., Khan, S., Khan, M., Akasha, R., Ashraf, J. M., . . . Khan, M. Y. (2022). Physicochemical Characterization of In Vitro LDL Glycation and Its Inhibition by Ellagic Acid (EA): An In Vivo Approach to Inhibit Diabetes in Experimental Animals. Biomed Res Int, 2022, 5583298. DOI: 10.1155/2022/5583298
Almowallad, S., Huwait, E., Al-Massabi, R., Saddeek, S., Gauthaman, K., & Prola, A. (2020). Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model. Pharmaceuticals (Basel), 13(11). DOI: 10.3390/ph13110372
Amin, M. M., & Arbid, M. S. (2017). Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats. Appl Physiol Nutr Metab, 42(2), 181-192. DOI: 10.1139/apnm-2016-0429
An, X., Zhang, Y., Cao, Y., Chen, J., Qin, H., & Yang, L. (2020). Punicalagin Protects Diabetic Nephropathy by Inhibiting Pyroptosis Based on TXNIP/NLRP3 Pathway. Nutrients, 12(5). DOI: 10.3390/nu12051516
Bardaweel, S. K., Gul, M., Alzweiri, M., Ishaqat, A., HA, A. L., & Bashatwah, R. M. (2018). Reactive Oxygen Species: the Dual Role in Physiological and Pathological Conditions of the Human Body. Eurasian J Med, 50(3), 193-201. DOI: 10.5152/eurasianjmed.2018.17397
Bate-Smith, E. C. (1962). The phenolic constituents of plants and their taxonomic significance. I. Dicotyledons. Journal of the Linnean Society of London, Botany, 58(371), 95-173. DOI: 10.1111/j.1095-8339.1962.tb00890.x
BenSaad, L. A., Kim, K. H., Quah, C. C., Kim, W. R., & 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. DOI: 10.1186/s12906-017-1555-0
Berdowska, I., Matusiewicz, M., & Fecka, I. (2021). Punicalagin in Cancer Prevention-Via Signaling Pathways Targeting. Nutrients, 13(8). DOI: 10.3390/nu13082733
Berkban, T., Boonprom, P., Bunbupha, S., Welbat, J. U., Kukongviriyapan, U., Kukongviriyapan, V., . Prachaney, P. (2015). Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats. Nutrients, 7(7), 5265-5280. DOI: 10.3390/nu7075222
Bialek, A., Jelinska, M., Bialek, M., Lepionka, T., Czerwonka, M., & Czauderna, M. (2020). The Effect of Diet Supplementation with Pomegranate and Bitter Melon on Lipidomic Profile of Serum and Cancerous Tissues of Rats with Mammary Tumours. Antioxidants (Basel), 9(3). DOI: 10.3390/antiox9030243
Borish, L. C., & Steinke, J. W. (2003). 2. Cytokines and chemokines. J Allergy Clin Immunol, 111(2 Suppl), S460-475. DOI: 10.1067/mai.2003.108
Busto, R., Serna, J., Perianes-Cachero, A., Quintana-Portillo, R., Garcia-Seisdedos, D., Canfran-Duque, A., . . Pastor, O. (2018). Ellagic acid protects from myelin-associated sphingolipid loss in experiment autoimmune encephalomyelitis. Biochim Biophys Acta Mol Cell Biol Lipids, 1863(9), 958-967. DOI:10.1016/j.bbalip.2018.05.009
Cerda, B., Tomas-Barberan, F. A., & Espin, J. C. (2005). Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability. J Agric Food Chem, 53(2), 227-235. DOI: 10.1021/jf049144d
Chao, P. C., Hsu, C. C., & Yin, M. C. (2009). Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice. Nutr Metab, 6, 33. DOI: 10.1186/1743-7075-6-33
Dhumal, S. S., Karale, A. R., Jadhav, S. B., & Kad, V. P. (2014). Recent advances and the developments in the pomegranate processing and utilization: a review. Journal of Agriculture and Crop Science, 1(1), 1-17.
Diaz, A., Munoz-Arenas, G., Caporal-Hernandez, K., Vazquez-Roque, R., Lopez-Lopez, G., Kozina, A., . . . Guevara, J. (2020). Gallic acid improves recognition memory and decreases oxidative-inflammatory damage in the rat hippocampus with metabolic syndrome. Synapse, 75(2), e22186. DOI: 10.1002/syn.22186
Ding, X., Jian, T., Wu, Y., Zuo, Y., Li, J., Lv, H., . . . Chen, J. (2019). Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway. Biomed Pharmacother, 110, 85-94. DOI: 10.1016/j.biopha.2018.11.018
Ding, Y., Zhang, B., Zhou, K., Chen, M., Wang, M., Jia, 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. DOI: 10.1016/j.ijcard.2014.06.045
Duan, J., Li, Y., Gao, H., Yang, D., He, X., Fang, Y., & Zhou, G. (2020). Phenolic compound ellagic acid inhibits mitochondrial respiration and tumor growth in lung cancer. Food Funct, 11(7), 6332-6339. DOI:10.1039/d0fo01177k
Espin, J. C., Larrosa, M., Garcia-Conesa, M. T., & 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. DOI: 10.1155/2013/270418
Falsaperla, M., Morgia, G., Tartarone, A., Ardito, R., & Romano, G. (2005). Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate. Eur Urol, 47(4), 449-454; discussion 454-445. DOI: 10.1016/j.eururo.2004.12.001
Fang, L., Wang, H., Zhang, J., & Fang, X. (2021). Punicalagin induces ROS-mediated apoptotic cell death through inhibiting STAT3 translocation in lung cancer A549 cells. J Biochem Mol Toxicol, 35(6), 1-10. DOI:10.1002/jbt.22771
Feng, X., Yang, Q., Wang, C., Tong, W., & Xu, W. (2020). Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF-kappaB-TH17/JAK2/STAT3 Signaling and Oxidative Stress. Biomed Res Int, 2020, 4918239. DOI: 10.1155/2020/4918239
Ferk, F., Kundi, M., Brath, H., Szekeres, T., Al-Serori, H., Misik, M., . . . Knasmueller, S. (2018). Gallic Acid Improves Health-Associated Biochemical Parameters and Prevents Oxidative Damage of DNA in Type 2 Diabetes Patients: Results of a Placebo-Controlled Pilot Study. Mol Nutr Food Res, 62(4). DOI:10.1002/mnfr.201700482
Fischer, U. A., Carle, R., & Kammerer, D. R. (2011). Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DADESI/MS(n). Food Chem, 127(2), 807-821. DOI: 10.1016/j.foodchem.2010.12.156
Fu, X., Gong, L. F., Wu, Y. F., Lin, Z., Jiang, B. J., Wu, L., & Yu, K. H. (2019). Urolithin A targets the PI3K/Akt/ NF-kappaB pathways and prevents IL-1beta-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies. Food Funct, 10(9), 6135-6146. DOI: 10.1039/c9fo01332f
Ganesan, T., Sinniah, A., Chik, Z., & Alshawsh, M. A. (2020). Punicalagin Regulates Apoptosis-Autophagy Switch via Modulation of Annexin A1 in Colorectal Cancer. Nutrients, 12(8). DOI: 10.3390/nu12082430
Garcia-Niño, W. R., & Zazueta, C. (2015). Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection. Pharmacol Res, 97, 84-103. DOI: 10.1016/j.phrs.2015.04.008
Ghadimi, M., Foroughi, F., Hashemipour, S., Rashidi Nooshabadi, M., Ahmadi, M. H., Ahadi Nezhad, B., & Khadem Haghighian, H. (2021). Randomized double-blind clinical trial examining the Ellagic acid effects on glycemic status, insulin resistance, antioxidant, and inflammatory factors in patients with type 2 diabetes. Phytother Res, 35(2), 1023-1032. DOI: 10.1002/ptr.6867
Gil, M. I., Tomas-Barberan, F. A., Hess-Pierce, B., Holcroft, D. M., & Kader, A. A. (2000). Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem, 48(10), 4581-4589. DOI: 10.1021/jf000404a
Griffith, J. W., Sokol, C. L., & Luster, A. D. (2014). Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol, 32, 659-702. DOI: 10.1146/annurevimmunol-032713-120145
Harakeh, S., Qari, M. H., Ramadan, W. S., Al Jaouni, S. K., Al Muhayawi, M. S., Al Amri, T., . . . Mousa, S. A. (2020). Novel Nano-formulations of Ellagic Acid are Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer’s Disease. Curr Drug Metab. DOI: 10.2174/1389200221666201216170851
He, L., He, T., Farrar, S., Ji, L., Liu, T., & Ma, X. (2017). Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol Biochem, 44(2), 532-553. DOI: 10.1159/000485089
Herb, M., Gluschko, A., & Schramm, M. (2021). Reactive Oxygen Species: Not Omnipresent but Important in Many Locations. Front Cell Dev Biol, 9, 716406. DOI: 10.3389/fcell.2021.716406
Hong, Z., Tang, P., Liu, B., Ran, C., Yuan, C., Zhang, Y., . . . Wu, H. (2021). Ferroptosis-related Genes for Overall Survival Prediction in Patients with Colorectal Cancer can be Inhibited by Gallic acid. Int J Biol Sci, 17(4),942-956. DOI: 10.7150/ijbs.57164
Huang, M., Wu, K., Zeng, S., Liu, W., Cui, T., Chen, Z., . . . Ouyang, H. (2021). Punicalagin Inhibited Inflammation and Migration of Fibroblast-Like Synoviocytes Through NF-kappaB Pathway in the Experimental Study of Rheumatoid Arthritis. J Inflamm Res, 14, 1901-1913. DOI: 10.2147/JIR.S302929
Huang, T., Zhang, X., & Wang, H. (2020). Punicalagin inhibited proliferation, invasion and angiogenesis of osteosarcoma through suppression of NFkappaB signaling. Mol Med Rep, 22(3), 2386 2394.DOI:10.3892/mmr.2020.11304
Islam, M. T. (2017). Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res, 39(1), 73-82. DOI: 10.1080/01616412.2016.1251711
Jin, L., Piao, Z. H., Sun, S., Liu, B., Kim, G. R., Seok, Y. M., . . . Jeong, M. H. (2017). Gallic Acid Reduces Blood Pressure and Attenuates Oxidative Stress and Cardiac Hypertrophy in Spontaneously Hypertensive Rats. Sci Rep, 7(1), 15607. DOI: 10.1038/s41598-017-15925-1
Jin, L., Sun, S., Ryu, Y., Piao, Z. H., Liu, B., Choi, S. Y., . . . Jeong, M. H. (2018). Gallic acid improves cardiac dysfunction and fibrosis in pressure overload-induced heart failure. Sci Rep, 8(1), 9302. DOI: 10.1038/ s41598-018-27599-4
Jones, D. P., & Sies, H. (2015). The Redox Code. Antioxid Redox Signal, 23(9), 734-746. DOI:10.1089/ars.2015.6247
Jordao, J. B. R., Porto, H. K. P., Lopes, F. M., Batista, A. C., & Rocha, M. L. (2017). Protective Effects of Ellagic Acid on Cardiovascular Injuries Caused by Hypertension in Rats. Planta Med, 83(10), 830-836. DOI:10.1055/s-0043-103281
Kaneto, H., Matsuoka, T. A., Katakami, N., Kawamori, D., Miyatsuka, T., Yoshiuchi, K., . . . Matsuhisa, M (2007). Oxidative stress and the JNK pathway are involved in the development of type 1 and type 2 diabetes. Curr Mol Med, 7(7), 674-686. DOI: 10.2174/156652407782564408
Kaur, R., Parveen, S., Mehan, S., & Kalra, S. (2015). Neuroprotective effect of ellagic acid against chronically scopolamine induced Alzheimer’s type memory and cognitive dysfunctions: Possible behavioural and biochemical evidences.
Kim, Y. E., Hwang, C. J., Lee, H. P., Kim, C. S., Son, D. J., Ham, Y. W., . . . Hong, J. T. (2017). Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology, 117, 21-32. DOI: 10.1016/j. neuropharm.2017.01.025
Klaunig, J. E. (2018). Oxidative Stress and Cancer. Curr Pharm Des, 24(40), 4771-4778. DOI: 10.2174/1381612825666190215121712
Kowalczyk, P., Sulejczak, D., Kleczkowska, P., Bukowska-Osko, I., Kucia, M., Popiel, M., . . . Kaczynska, K. (2021). Mitochondrial Oxidative Stress-A Causative Factor and Therapeutic Target in Many Diseases. Int J Mol Sci, 22(24). DOI: 10.3390/ijms222413384
Kujawska, M., Jourdes, M., Kurpik, M., Szulc, M., Szaefer, H., Chmielarz, P., . . . Jodynis-Liebert, J. (2019). Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins- Derived Metabolite-Urolithin A-In the Brain. Int J Mol Sci, 21(1). DOI: 10.3390/ijms21010202
Kumar, H., Kim, I. S., More, S. V., Kim, B. W., & Choi, D. K. (2014). Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep, 31(1), 109-139. DOI:10.1039/c3np70065h
Kumar, M., & Bansal, N. (2018). Ellagic acid prevents dementia through modulation of PI3-kinaseendothelial nitric oxide synthase signalling in streptozotocin-treated rats. Naunyn Schmiedebergs Arch Pharmacol, 391(9), 987-1001. DOI: 10.1007/s00210-018-1524-2
Larrosa, M., Gonzalez-Sarrias, A., Yanez-Gascon, M. J., Selma, M. V., Azorin-Ortuno, M., Toti, S., . . . Espin, J. C. (2010). Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J Nutr Biochem, 21(8), 717-725. DOI: 10.1016/j.jnutbio.2009.04.012
Li, M., Kai, Y., Qiang, H., & Dongying, J. (2006). Biodegradation of gallotannins and ellagitannins. J Basic Microbiol, 46(1), 68-84. DOI: 10.1002/jobm.200510600
Lin, Z., Lin, C., Fu, C., Lu, H., Jin, H., Chen, Q., & Pan, J. (2020). The protective effect of Ellagic acid (EA) in osteoarthritis: An in vitro and in vivo study. Biomed Pharmacother, 125, 109845. DOI:10.1016/j.biopha.2020.109845
Liu, J., Jiang, J., Qiu, J., Wang, L., Zhuo, J., Wang, B., . . . Lou, H. (2022). Urolithin A protects dopaminergic neurons in experimental models of Parkinson’s disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1alpha signaling pathway. Food Funct, 13(1), 375-385. DOI: 10.1039/d1fo02534a
Lorenzo, J. M., Munekata, P. E., Putnik, P., Kovačević, D. B., Muchenje, V., & Barba, F. J. (2019). Chapter 6- Sources, Chemistry, and Biological Potential of Ellagitannins and Ellagic Acid Derivatives. In Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry (Vol. 60, pp. 189-221). Elsevier. DOI: 10.1016/B978-0-444-64181-6.00006-1
Lorenzon Dos Santos, J., Quadros, A. S., Weschenfelder, C., Garofallo, S. B., & Marcadenti, A. (2020). Oxidative Stress Biomarkers, Nut-Related Antioxidants, and Cardiovascular Disease. Nutrients, 12(3). DOI:10.3390/nu12030682
Magangana, T. P., Makunga, N. P., Fawole, O. A., & Opara, U. L. (2020). Processing Factors Affecting the Phytochemical and Nutritional Properties of Pomegranate (Punica granatum L.) Peel Waste: A Review. Molecules, 25(20). DOI: 10.3390/molecules25204690
Malik, A., Afaq, S., Shahid, M., Akhtar, K., & Assiri, A. (2011). Influence of ellagic acid on prostate cancer cell proliferation: a caspase-dependent pathway. Asian Pac J Trop Med, 4(7), 550-555. DOI: 10.1016/S19957645(11)60144-2
Mansouri, Z., Dianat, M., Radan, M., & Badavi, M. (2020). Ellagic Acid Ameliorates Lung Inflammation and Heart Oxidative Stress in Elastase-Induced Emphysema Model in Rat. Inflammation, 43(3), 1143-1156. DOI:10.1007/s10753-020-01201-4
Marin, M., Maria Giner, R., Rios, J. L., & Recio, M. C. (2013). Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis. J Ethnopharmacol, 150(3), 925-934. DOI: 10.1016/j.jep.2013.09.030
Maritim, A. C., Sanders, R. A., & Watkins, J. B., 3rd. (2003). Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol, 17(1), 24-38. DOI: 10.1002/jbt.10058
Mironczuk-Chodakowska, I., Witkowska, A. M., & Zujko, M. E. (2018). Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci, 63(1), 68-78. DOI: 10.1016/j.advms.2017.05.005
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.DOI: 10.3109/10428194.2011.591014
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. DOI: 10.1186/s12906-0150810-5
Moga, M. A., Dimienescu, O. G., Balan, A., Dima, L., Toma, S. I., Bigiu, N. F., & Blidaru, A. (2021). Pharmacological and Therapeutic Properties of Punica granatum Phytochemicals: Possible Roles in Breast Cancer. Molecules, 26(4). DOI: 10.3390/molecules26041054
Ongoz Dede, F., Bozkurt Dogan, S., Balli, U., Durmuslar, M. C., Avci, B., Gulle, K., & Akpolat Ferah, M. (2021). The effect of ellagic acid on the repair process of periodontal defects related to experimental periodontitis in rats. J Appl Oral Sci, 29, e20210160. DOI: 10.1590/1678-7757-2021-0160
Panchal, S. K., Ward, L., & Brown, L. (2013). Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Eur J Nutr, 52(2), 559-568. DOI: 10.1007/s00394-012-0358-9
Patel, S. S., & Goyal, R. K. (2011). Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats. Pharmacognosy Res, 3(4), 239-245. DOI: 10.4103/0974-8490.89743
Pfundstein, B., El Desouky, S. K., Hull, W. E., Haubner, R., Erben, G., & Owen, R. W. (2010). Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities. Phytochemistry, 71(10), 1132-1148. DOI: 10.1016/j.phytochem.2010.03.018
Pisoschi, A. M., & Pop, A. (2015). The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem, 97, 55-74. DOI: 10.1016/j.ejmech.2015.04.040
Piwowarski, J. P., Kiss, A. K., Granica, S., & Moeslinger, T. (2015). Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages. Mol Nutr Food Res, 59(11), 2168-2177. DOI: 10.1002/mnfr.201500264
Polce, S. A., Burke, C., Franca, L. M., Kramer, B., de Andrade Paes, A. M., & Carrillo-Sepulveda, M. A. (2018). Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats. Nutrients, 10(5). DOI: 10.3390/nu10050531
Powers, S. K., DeRuisseau, K. C., Quindry, J., & Hamilton, K. L. (2004). Dietary antioxidants and exercise. J Sports Sci, 22(1), 81-94. DOI: 10.1080/0264041031000140563
Qiu, J., Chen, Y., Zhuo, J., Zhang, L., Liu, J., Wang, B., . . . Lou, H. (2022). Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson’s disease model. Neuropharmacology, 207, 108963. DOI:10.1016/j.neuropharm.2022.108963
Qiu, Z., Zhou, B., Jin, L., Yu, H., Liu, L., Liu, Y., . . . 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. DOI: 10.1016/j.fct.2013.06.025
Quiros-Fernandez, R., Lopez-Plaza, B., Bermejo, L. M., Palma-Milla, S., & Gomez-Candela, C. (2019). Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial. Nutrients, 11(3). DOI: 10.3390/nu11030640
Ramadan, W. S., & Alkarim, S. (2021). Ellagic Acid Modulates the Amyloid Precursor Protein Gene via Superoxide Dismutase Regulation in the Entorhinal Cortex in an Experimental Alzheimer’s Model. Cells, 10(12). DOI: 10.3390/cells10123511
Reuter, S., Gupta, S. C., Chaturvedi, M. M., & Aggarwal, B. B. (2010). Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med, 49(11), 1603-1616. DOI:10.1016/j.freeradbiomed.2010.09.006
Rosillo, M. A., Sanchez-Hidalgo, M., Cardeno, A., Aparicio-Soto, M., Sanchez-Fidalgo, S., Villegas, I., & de la Lastra, C. A. (2012). Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol Res, 66(3), 235-242. DOI: 10.1016/j.phrs.2012.05.006
Rosillo, M. A., Sanchez-Hidalgo, M., Cardeno, A., & de la Lastra, C. A. (2011). Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn’s disease. Biochem Pharmacol, 82(7), 737- 745. DOI: 10.1016/j.bcp.2011.06.043
Sadiq, I. Z. (2021). Free radicals and oxidative stress: signaling mechanisms, redox basis for human diseases, and cell cycle regulation. Curr Mol Med. DOI: 10.2174/1566524022666211222161637
Sarkaki, A., Farbood, Y., Dolatshahi, M., Mansouri, S. M., & Khodadadi, A. (2016). Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson’s Disease. Acta Med Iran, 54(8), 494-502. https://www.ncbi.nlm.nih.gov/pubmed/27701719
Savi, M., Bocchi, L., Mena, P., Dall’Asta, M., Crozier, A., Brighenti, F., . . . Del Rio, D. (2017). In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats. Cardiovasc Diabetol, 16(1), 80. DOI: 10.1186/s12933-017-0561-3
Seeram, N. P., Lee, R., Hardy, M., & Heber, D. (2005). Rapid large scale purification of ellagitannins from pomegranate husk, a by-product of the commercial juice industry. Separation and Purification Technology, 41, 49-55. DOI: 10.1016/j.seppur.2004.04.003
Senoner, T., & Dichtl, W. (2019). Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target? Nutrients, 11(9). DOI: 10.3390/nu11092090
Sepúlveda, L., Aguilera-Carbó, A., Ascacio-Valdés, J. A., Rodríguez-Herrera, R., Martínez-Hernández, J. L., & Aguilar, C. N. (2012). Optimization of ellagic acid accumulation by Aspergillus niger GH1 in solid state culture using pomegranate shell powder as a support. Process Biochemistry, 47(12), 2199-2203.
Sepúlveda, L., Ascacio, A., Rodríguez-Herrera, R., Aguilera-Carbó, A., & Aguilar, C. N. (2011). Ellagic acid: biological properties and biotechnological development for production processes. Afr. J. Biotechnol, 10, 4518–4523. DOI: 10.5897/AJB10.2201
Sharma, P., Kumar, M., & Bansal, N. (2021). Ellagic acid prevents 3-nitropropionic acid induced symptoms of Huntington’s disease. Naunyn Schmiedebergs Arch Pharmacol, 394(9), 1917-1928. DOI: 10.1007/s00210021-02106-1
Shepherd, A. G., Manson, M. M., Ball, H. W., & McLellan, L. I. (2000). Regulation of rat glutamate-cysteine ligase (gamma-glutamylcysteine synthetase) subunits by chemopreventive agents and in aflatoxin B(1)- induced preneoplasia. Carcinogenesis, 21(10), 1827-1834. DOI: 10.1093/carcin/21.10.1827
Siddiqui, S., Kamal, A., Khan, F., Jamali, K. S., & Saify, Z. S. (2019). Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration. Mol Biol Rep, 46(1), 997-1011. DOI: 10.1007/s11033-018-4557-1
Sies, H. (2015). Oxidative stress: a concept in redox biology and medicine. Redox Biol, 4, 180-183. DOI: 10.1016/j.redox.2015.01.002
Singh, K., Jaggi, A. S., & Singh, N. (2009). Exploring the ameliorative potential of Punica granatum in dextran sulfate sodium induced ulcerative colitis in mice. Phytother Res, 23(11), 1565-1574. DOI: 10.1002/ptr.2822
Sinha, N., & Dabla, P. K. (2015). Oxidative stress and antioxidants in hypertension-a current review. Curr Hypertens Rev, 11(2), 132-142. DOI: 10.2174/1573402111666150529130922
Sohrabi, F., Dianat, M., Badavi, M., Radan, M., & Mard, S. A. (2021). Gallic acid suppresses inflammation and oxidative stress through modulating Nrf2-HO-1-NF-kappaB signaling pathways in elastase-induced} emphysema in rats. Environ Sci Pollut Res Int, 28(40), 56822-56834. DOI: 10.1007/s11356-021-14513-1
Stover, E., & Mercure, E. W. (2007). The pomegranate: a new look at the fruit of paradise. HortScience horts, 42(5), 1088-1092. DOI: 10.21273/HORTSCI.42.5.1088
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. DOI: 10.1007/s10620-008-0423-7
Sylla, T., Pouysegu, L., Da Costa, G., Deffieux, D., Monti, J. P., & Quideau, S. (2015). Gallotannins and Tannic Acid: First Chemical Syntheses and In Vitro Inhibitory Activity on Alzheimer’s Amyloid beta-Peptide Aggregation. Angew Chem Int Ed Engl, 54(28), 8217-8221. DOI: 10.1002/anie.201411606
Tang, B., Chen, G. X., Liang, M. Y., Yao, J. P., & Wu, Z. K. (2015). Ellagic acid prevents monocrotaline-induced pulmonary artery hypertension via inhibiting NLRP3 inflammasome activation in rats. Int J Cardiol, 180, 134-141. DOI: 10.1016/j.ijcard.2014.11.161
Uzar, E., Alp, H., Cevik, M. U., 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. DOI: 10.1007/s10072-011-0775-1
Wahlqvist, M. L. (2013). Antioxidant relevance to human health. Asia Pac J Clin Nutr, 22(2), 171-176. DOI: 10.6133/apjcn.2013.22.2.21
Wang, L., Li, W., Lin, M., Garcia, M., Mulholland, D., Lilly, M., & Martins-Green, M. (2014). Luteolin, ellagic acid and punicic acid are natural products that inhibit prostate cancer metastasis. Carcinogenesis, 35(10), 2321-2330. DOI: 10.1093/carcin/bgu145
Wang, Y., Huang, M., Yang, X., Yang, Z., Li, L., & Mei, J. (2018). Supplementing punicalagin reduces oxidative stress markers and restores angiogenic balance in a rat model of pregnancy-induced hypertension. Korean J Physiol Pharmacol, 22(4), 409-417. DOI: 10.4196/kjpp.2018.22.4.409
Wang, Y., Qiu, Z., Zhou, B., Liu, C., Ruan, J., Yan, Q., . . . Zhu, F. (2015). In vitro antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells. Toxicol In Vitro, 29(5), 1107-1115. DOI: 10.1016/j.tiv.2015.04.008
Wei, D. Z., Lin, C., Huang, Y. Q., Wu, L. P., & Huang, M. Y. (2017). Ellagic acid promotes ventricular remodeling after acute myocardial infarction by up-regulating miR-140-3p. Biomed Pharmacother, 95, 983-989. DOI:10.1016/j.biopha.2017.07.106
Wei, Y. Z., Zhu, G. F., Zheng, C. Q., Li, J. J., Sheng, S., Li, D. D., . . . Zhang, F. (2020). Ellagic acid protects dopamine neurons from rotenone-induced neurotoxicity via activation of Nrf2 signalling. J Cell Mol Med, 24(16), 9446-9456. DOI: 10.1111/jcmm.15616
Wu, S., & Tian, L. (2017). Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum). Molecules, 22(10). DOI: 10.3390/molecules22101606
Yan, L., Yin, P., Ma, C., & Liu, Y. (2014). Method development and validation for pharmacokinetic and tissue distributions of ellagic acid using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Molecules, 19(11), 18923-18935. DOI: 10.3390/molecules191118923
Yan, X., Zhang, Q. Y., Zhang, Y. L., Han, X., Guo, S. B., & Li, H. H. (2020). Gallic Acid Attenuates Angiotensin IIInduced Hypertension and Vascular Dysfunction by Inhibiting the Degradation of Endothelial Nitric Oxide Synthase. Front Pharmacol, 11, 1121. DOI: 10.3389/fphar.2020.01121
Yu, L. M., Dong, X., Xue, X. D., Zhang, J., Li, Z., Wu, H. J., . . . Wang, H. S. (2019). Protection of the myocardium against ischemia/reperfusion injury by punicalagin through an SIRT1-NRF-2-HO-1-dependent mechanism. Chem Biol Interact, 306, 152-162. DOI: 10.1016/j.cbi.2019.05.003
Yu, Y. M., Chang, W. C., Wu, C. H., & Chiang, S. Y. (2005). Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J Nutr Biochem, 16(11), 675-681. DOI: 10.1016/j.jnutbio.2005.03.013
Zhang, L., Chinnathambi, A., Alharbi, S. A., Veeraraghavan, V. P., Mohan, S. K., & Zhang, G. (2020). Punicalagin promotes the apoptosis in human cervical cancer (ME-180) cells through mitochondrial pathway and by inhibiting the NF-kB signaling pathway. Saudi J Biol Sci, 27(4), 1100-1106. DOI:10.1016/j.sjbs.2020.02.015
Zhang, Y., Cao, Y., Chen, J., Qin, H., & Yang, L. (2019). A New Possible Mechanism by Which Punicalagin Protects against Liver Injury Induced by Type 2 Diabetes Mellitus: Upregulation of Autophagy via the Akt/ FoxO3a Signaling Pathway. J Agric Food Chem, 67(50), 13948-13959. DOI: 10.1021/acs.jafc.9b05910
Zhu, L., Gu, P., & Shen, H. (2019). Gallic acid improved inflammation via NF-kappaB pathway in TNBSinduced ulcerative colitis. Int Immunopharmacol, 67, 129-137. DOI: 10.1016/j.intimp.2018.11.049
Zou, X., Yan, C., Shi, Y., Cao, K., Xu, J., Wang, X., . . . Feng, Z. (2014). Mitochondrial dysfunction in obesityassociated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin. Antioxid Redox Signal, 21(11), 1557-1570. DOI: 10.1089/ars.2013.5538