Physiological Function of Hydroxytyrosol and Its Application Prospect in Animal Production

  • DENG Shengting ,
  • WANG Yujie ,
  • LIU Shuangli ,
  • CHEN Qinghua
Expand
  • College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China

Received date: 2019-11-16

  Online published: 2020-05-15

Abstract

Hydroxytyrosol is a phenolic substance mainly existing in olives and their processed products. It has strong antioxidant, cancer prevention, antibacterial, anti-inflammatory, lipids lowering and other physiological functions. Moreover, it has high bio-absorption and utilization rate. This review summarizes the origin, synthesis, digestion, absorption and metabolism of hydroxytyrosol, as well as its main physiological functions and mechanism, and its application prospect in animal production, so as to provide theoretical basis and guidance for the development and application of hydroxytyrosol in animal production.

Cite this article

DENG Shengting , WANG Yujie , LIU Shuangli , CHEN Qinghua . Physiological Function of Hydroxytyrosol and Its Application Prospect in Animal Production[J]. Chinese Journal of Animal Nutrition, 2020 , 32(5) : 2027 -2036 . DOI: 10.3969/j.issn.1006-267x.2020.05.010

References

[1] BRITTON J,DAVIS R,O'CONNOR K E.Chemical,physical and biotechnological approaches to the production of the potent antioxidant hydroxytyrosol[J].Applied Microbiology and Biotechnology,2019,103(15):5957-5974.  
[2] ROBLES-ALMAZAN M,PULIDO-MORAN M,MORENO-FERNANDEZ J,et al.Hydroxytyrosol:bioavailability,toxicity,and clinical applications[J].Food Research International,2018,105:654-667.
[3] OWEN R W,MIER W,GIACOSA A,et al.Phenolic compounds and squalene in olive oils:the concentration and antioxidant potential of total phenols,simple phenols,secoiridoids,lignansand squalene[J].Food and Chemical Toxicology,2000,38(8):647-659.  
[4] CHAROENPRASERT S,MITCHELL A.Factors influencing phenolic compounds in table olives (Olea europaea)[J].Journal of Agricultural and Food Chemistry,2012,60(29):7081-7095.  
[5] BRENES M,GARCÍA A,GARCÍA P,et al.Phenolic compounds in Spanish olive oils[J].Journal of Agricultural and Food Chemistry,1999,47(9):3535-3540.  
[6] MOTILVA M J,MACIÀ A,ROMERO M P,et al.Human bioavailability and metabolism of phenolic compounds from red wine enriched with free or nano-encapsulated phenolic extract[J].Journal of Functional Foods,2016,25:80-93.
[7] RODRÍGUEZ-MORATÓ J,XICOTA L,FITÓ M,et al.Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases[J].Molecules,2015,20(3):4655-4680.  
[8] PEREIRA-CARO G,SARRIÁ B,MADRONA A,et al.Digestive stability of hydroxytyrosol,hydroxytyrosyl acetate and alkyl hydroxytyrosyl ethers[J].International Journal of Food Sciences and Nutrition,2012,63(6):703-707.  
[9] MANNA C,GALLETTI P,MAISTO G,et al.Transport mechanism and metabolism of olive oil hydroxytyrosol in Caco-2 cells[J].FEBS Letters,2000,470(3):341-344.  
[10] VISSERS M N,ZOCK P L,ROODENBURG A J C,et al.Olive oil phenols are absorbed in humans[J].The Journal of Nutrition,2002,132(3):409-417.  
[11] GRANADOS-PRINCIPAL S,QUILES J L,RAMIREZ-TORTOSA C L,et al.Hydroxytyrosol:from laboratory investigations to future clinical trials[J].Nutrition Reviews,2010,68(4):191-206.  
[12] TUCK K L,FREEMAN M P,HAYBALL P J,et al.The in vivo fate of hydroxytyrosol and tyrosol,antioxidant phenolic constituents of olive oil,after intravenous and oral dosing of labeled compounds to rats[J].The Journal of Nutrition,2001,131(7):1993-1996.  
[13] GONZALEZ-SANTIAGO M,FONOLLÁ J,LOPEZ-HUERTAS E.Human absorption of a supplement containing purified hydroxytyrosol,a natural antioxidant from olive oil,and evidence for its transient association with low-density lipoproteins[J].Pharmacological Research,2010,61(4):364-370.  
[14] DE BOCK M,THORSTENSEN E B,DERRAIK J G B,et al.Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract[J].Molecular Nutrition & Food Research,2013,57(11):2079-2085.  
[15] DOMÍNGUEZ-PERLES R,AUÑÓN D,FERRERES F,et al.Gender differences in plasma and urine metabolites from Sprague-Dawley rats after oral administration of normal and high doses of hydroxytyrosol,hydroxytyrosol acetate,and DOPAC[J].European Journal of Nutrition,2017,56(1):215-224.  
[16] SUÁREZ M,VALLS R M,ROMERO M P,et al.Bioavailability of phenols from a phenol-enriched olive oil[J].British Journal of Nutrition,2011,106(11):1691-1701.  
[17] FERNÁNDEZ-ÁVILA C,MONTES R,CASTELLOTE A I,et al.Fast determination of virgin olive oil phenolic metabolites in human high-density lipoproteins[J].Biomedical Chromatography,2015,29(7):1035-1041.  
[18] D'ANGELO S,MANNA C,MIGLIARDI V,et al.Pharmacokinetics and metabolism of hydroxytyrosol,a natural antioxidant from olive oil[J].Drug Metabolism and Disposition,2001,29(11):1492-1498.
[19] WU Y T,LIN L C,TSAI T H.Measurement of free hydroxytyrosol in microdialysates from blood and brain of anesthetized rats by liquid chromatography with fluorescence detection[J].Journal of Chromatography A,2009,1216(16):3501-3507.  
[20] RUBIO L,MACIÀ A,VALLS R M,et al.A new hydroxytyrosol metabolite identified in human plasma:hydroxytyrosol acetate sulphate[J].Food Chemistry,2012,134(2):1132-1136.  
[21] SERRA A,RUBIO L,BORRÀS X,et al.Distribution of olive oil phenolic compounds in rat tissues after administration of a phenolic extract from olive cake[J].Molecular Nutrition & Food Research,2012,56(3):486-496.  
[22] DE LA TORRE R,COVAS M I,PUJADAS M A,et al.Is dopamine behind the health benefits of red wine?[J].European Journal of Nutrition,2006,45(5):307-310.  
[23] SCHAFFER S,MÜELLER W E,ECKERT G P.Cytoprotective effects of olive mill wastewater extract and its main constituent hydroxytyrosol in PC12 cells[J].Pharmacological Research,2010,62(4):322-327.  
[24] COVAS M I,DE LA TORRE R,FITÓ M.Virgin olive oil:a key food for cardiovascular risk protection[J].British Journal of Nutrition,2015,113(Suppl.2):S19-S28.
[25] MARTINEZ L,ROS G,NIETO G.Hydroxytyrosol:health benefits and use as functional ingredient in meat[J].Medicines,2018,5(1):13.
[26] DE LA CRUZ J P,RUIZ-MORENO M I,GUERRERO A,et al.Role of the catechol group in the antioxidant and neuroprotective effects of virgin olive oil components in rat brain[J].The Journal of Nutritional Biochemistry,2015,26(5):549-555.  
[27] VISIOLI F,POLI A,GALL C.Antioxidant and other biological activities of phenols from olives and olive oil[J].Medicinal Research Reviews,2002,22(1):65-75.  
[28] DEIANA M,INCANI A,ROSA A,et al.Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H2O2 induced oxidative damage[J].Chemico-Biological Interactions,2011,193(3):232-239.  
[29] PAIVA-MARTINS F,SILVA A,ALMEIDA V,et al.Protective activity of hydroxytyrosol metabolites on erythrocyte oxidative-induced hemolysis[J].Journal of Agricultural and Food Chemistry,2013,61(27):6636-6642.  
[30] RODRIGUEZ-RAMIRO I,MARTÍN M Á,RAMOS S,et al.Olive oil hydroxytyrosol reduces toxicity evoked by acrylamide in human Caco-2 cells by preventing oxidative stress[J].Toxicology,2011,288(1/2/3):43-48.
[31] ILAVARASI K,KIRUTHIGA P V,PANDIAN S K,et al.Hydroxytyrosol,the phenolic compound of olive oil protects human PBMC against oxidative stress and DNA damage mediated by 2,3,7,8-TCDD[J].Chemosphere,2011,84(7):888-893.  
[32] ZHU L,LIU Z B,FENG Z H,et al.Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase Ⅱ detoxifying enzyme systems in retinal pigment epithelial cells[J].Journal of Nutritional Biochemistry,2010,21(11):1089-1098.  
[33] MARTÍN M A,RAMOS S,GRANADO-SERRANO A B,et al.Hydroxytyrosol induces antioxidant/detoxificant enzymes and Nrf2 translocation via extracellular regulated kinases and phosphatidylinositol-3-kinase/protein kinase B pathways in HepG2 cells[J].Molecular Nutrition & Food Research,2010,54(7):956-966.  
[34] SAXENA N K,SHARMA D,DING X K,et al.Concomitant activation of the JAK/STAT,PI3K/AKT,and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells[J].Cancer Research,2007,67(6):2497-2507.  
[35] ZHAO B L,MA Y,XU Z L,et al.Hydroxytyrosol,a natural molecule from olive oil,suppresses the growth of human hepatocellular carcinoma cells via inactivating AKT and nuclear factor-kappa B pathways[J].Cancer Letters,2014,347(1):79-87.  
[36] NOTARNICOLA M,PISANTI S,TUTINO V,et al.Effects of olive oil polyphenols on fatty acid synthase gene expression and activity in human colorectal cancer cells[J].Genes and Nutrition,2011,6(1):63-69.  
[37] FABIANI R,ROSIGNOLI P,DE BARTOLOMEO A,et al.Inhibition of cell cycle progression by hydroxytyrosol is associated with upregulation of cyclin-dependent protein kinase inhibitors p21WAF1/Cip1 and p27Kip1 and with induction of differentiation in HL60 cells[J].The Journal of Nutrition,2008,138(1):42-48.  
[38] SIRIANNI R,CHIMENTO A,DE LUCA A,et al.Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation[J].Molecular Nutrition & Food Research,2010,54(6):833-840.
[39] LUO C,LI Y,WANG H,et al.Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells[J].Current Cancer Drug Targets,2013,13(6):625-639.  
[40] BISIGNANO G,TOMAINO A,LO CASCIO R,et al.On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol[J].The Journal of Pharmacy and Pharmacology,1999,51(8):971-974.  
[41] DE LEONARDIS A,ARETINI A,ALFANO G,et al.Isolation of a hydroxytyrosol-rich extract from olive leaves (Olea Europaea L.) and evaluation of its antioxidant properties and bioactivity[J].European Food Research and Technology,2008,226(4):653-659.  
[42] AISSA I,KHARRAT N,ALOUI F,et al.Valorization of antioxidants extracted from olive mill wastewater[J].Biotechnology and Applied Biochemistry,2017,64(4):579-589.  
[43] MEDINA-MARTÍNEZ M S,TRUCHADO P,CASTRO-IBÁÑEZ I,et al.Antimicrobial activity of hydroxytyrosol:a current controversy[J].Bioscience,Biotechnology,and Biochemistry,2016,80(4):801-810.  
[44] DIALLINAS G,RAFAILIDOU N,KALPAKTSI I,et al.Hydroxytyrosol (HT) analogs act as potent antifungals by direct disruption of the fungal cell membrane[J].Frontiers in Microbiology,2018,9:2624.
[45] YAO F,YANG G D,XIAN Y S,et al.The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway[J].Food & Function,2019,10(9):5789-5803.  
[46] YONEZAWA Y,KIHARA T,IBI K,et al.Olive-derived hydroxytyrosol shows anti-inflammatory effect without gastric damage in rats[J].Biological and Pharmaceutical Bulletin,2019,42(7):1120-1127.  
[47] SCODITTI E,MASSARO M,CARLUCCIO M A,et al.Additive regulation of adiponectin expression by the mediterranean diet olive oil components oleic acid and hydroxytyrosol in human adipocytes[J].PLoS One,2015,10(6):e0128218.
[48] LIU Z Q,WANG N N,MA Y N,et al.Hydroxytyrosol improves obesity and insulin resistance by modulating gut microbiota in high-fat diet-induced obese mice[J].Frontiers in Microbiology,2019,10:390.
[49] GINER E,ANDÚJAR I,RECIO M C,et al.Oleuropein ameliorates acute colitis in mice[J].Journal of Agricultural and Food Chemistry,2011,59(24):12882-12892.  
[50] SERRELI G,MELIS M P,CORONA G,et al.Modulation of LPS-induced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites:insight into the mechanism of action[J].Food and Chemical Toxicology,2019,125:520-527.
[51] DRIRA R,SAKAMOTO K.Modulation of adipogenesis,lipolysis and glucose consumption in 3T3-L1 adipocytes and C2C12 myotubes by hydroxytyrosol acetate:a comparative study[J].Biochemical and Biophysical Research Communications,2013,440(4):576-581.  
[52] DRIRA R,SAKAMOTO K.Hydroxytyrosol stimulates lipolysis via A-kinase and extracellular signal-regulated kinase activation in 3T3-L1 adipocytes[J].European Journal of Nutrition,2014,53(3):743-750.  
[53] STEFANON B,COLITTI M.Original research:hydroxytyrosol,an ingredient of olive oil,reduces triglyceride accumulation and promotes lipolysis in human primary visceral adipocytes during differentiation[J].Experimental Biology and Medicine,2016,241(16):1796-1802.  
[54] SCODITTI E,CARPI S,MASSARO M,et al.Hydroxytyrosol modulates adipocyte gene and miRNA expression under inflammatory condition[J].Nutrients,2019,11(10):2493.
[55] GARCIA-CONTRERAS C,VAZQUEZ-GOMEZ M,PARDO Z,et al.Polyphenols and IUGR pregnancies:effects of maternal hydroxytyrosol supplementation on hepatic fat accretion and energy and fatty acids profile of fetal tissues[J].Nutrients,2019,11(7):1534.
[56] ECHEVERRÍA F,VALENZUELA R,BUSTAMANTE A,et al.Attenuation of high-fat diet-induced rat liver oxidative stress and steatosis by combined hydroxytyrosol- (HT-) eicosapentaenoic acid supplementation mainly relies on HT[J].Oxidative Medicine and Cellular Longevity,2018,2018:5109503.
[57] LUCAS R,COMELLES F,ALCÁNTARA D,et al.Surface-active properties of lipophilic antioxidants tyrosol and hydroxytyrosol fatty acid esters:a potential explanation for the nonlinear hypothesis of the antioxidant activity in oil-in-water emulsions[J].Journal of Agricultural and Food Chemistry,2010,58(13):8021-8026.  
[58] WANG N N,LIU Y,MA Y N,et al.Hydroxytyrosol ameliorates insulin resistance by modulating endoplasmic reticulum stress and prevents hepatic steatosis in diet-induced obesity mice[J].The Journal of Nutritional Biochemistry,2018,57:180-188.
[59] GAVAHIAN M,KHANEGHAH A M,LORENZO J M,et al.Health benefits of olive oil and its components:impacts on gut microbiota antioxidant activities,and prevention of noncommunicable diseases[J].Trends in Food Science & Technology,2019,88:220-227.
[60] DEIANA M,SERRA G,CORONA G.Modulation of intestinal epithelium homeostasis by extra virgin olive oil phenolic compounds[J].Food & Function,2018,9(8):4085-4099.  
[61] PAN S H,LIU L X,PAN H Y,et al.Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice[J].Molecular Nutrition & Food Research,2013,57(7):1218-1227.  
[62] BHOGAL R H,CURBISHLEY S M,WESTON C J,et al.Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation[J].Liver Transplantation,2010,16(11):1303-1313.  
[63] ECHEVERRIA F,VALENZUELA R,BUSTAMANTE A,et al.High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism:attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration[J].Food & Function,2019,10(9):6170-6183.  
[64] SOTO-ALARCÓN S A,ORTIZ M,ORELLANA P,et al.Docosahexaenoic acid and hydroxytyrosol co-administration fully prevents liver steatosis and related parameters in mice subjected to high-fat diet:a molecular approach[J].Biofactors,2019,45(6):930-943.  
[65] PRIORE P,SICULELLA L,GNONI G V.Extra virgin olive oil phenols down-regulate lipid synthesis in primary-cultured rat-hepatocytes[J].Journal of Nutritional Biochemistry,2014,25(7):683-691.  
[66] RUBIO-SENENT F,DE ROOS B,DUTHIE G,et al.Inhibitory and synergistic effects of natural olive phenols on human platelet aggregation and lipid peroxidation of microsomes from vitamin E-deficient rats[J].European Journal of Nutrition,2015,54(8):1287-1295.  
[67] RODRÍGUEZ-GUTIÉRREZ G,RUBIO-SENENT F,GÓMEZ-CARRETERO A,et al.Selenium and sulphur derivatives of hydroxytyrosol:inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats[J].European Journal of Nutrition,2019,58(5):1847-1851.  
[68] CAI W J,CHEN Y,SHI L X,et al.AKT-GSK3β signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage contributing to osteoblast apoptosis:preventative effects of hydroxytyrosol[J].Oxidative Medicine and Cellular Longevity,2019,2019:4101738.
[69] MAHMOUDI A,GHORBEL H,FEKI I,et al.Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism[J].Biomedicine & Pharmacotherapy,2018,103:1115-1126.
[70] ANTER J,QUESADA-GÓMEZ J M,DORADO G,et al.Effect of hydroxytyrosol on human mesenchymal stromal/stem cell differentiation into adipocytes and osteoblasts[J].Archives of Medical Research,2016,47(3):162-171.  
Outlines

/