**1. Introduction**

374 Olive Oil – Constituents, Quality, Health Properties and Bioconversions

Scarmeas, N., Luchsinger, J. A., Schupf, N., Brickman, A. M., Cosentino, S., Tang, M. X., et al.

Scher, J., Pillinger, M. & Abramson, S. 2007. Nitric oxide synthases and osteoarthritis.

Servili, M., Esposto, S., Londolini, E., Selvaggini, R., Taticchi, A., Urbani, S., et al. 2007a.

Sroka, Z. & Cisowski, W. 2003. Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids. *Food and Chemical Toxicology,* 41, 753-758. Stark, A. H. & Madar, Z. 2002. Olive oil as a functional food: epidemiology and nutritional

Subbaramaiah, K., Norton, L., Gerald, W. & Dannenberg, A. J. 2002. Cyclooxygenase-2 is

Tortosa, A., Bes-Rastrollo, M., Sanchez-Villegas, A., Basterra-Gortari, F. J., Nunez-Cordoba,

with the incidence of metabolic syndrome. *Diabetes Care,* 30, 2957-2959. Tovar, M. J., Motilva, M. J. & Romero, M. P. 2001. Changes in the phenolic composition of

*Medical Association,* 302, 627-637.

*Current Rheumatology Reports,* 9, 9-15.

*Agricultural and Food Chemistry,* 55, 7028-7035.

approaches. *Nutrition Reviews,* 60, 170-176.

cohort study. *British Medical Journal,* 330, 991-998.

277, 18649 - 18657.

10, 5-12.

pages- 383-388.

1218-1223.

2009. Physical activity, diet, and risk of Alzheimer disease. *Journal of American* 

Irrigation effects on quality, phenolic composition, and selected volatiles of virgin olive oils Cv. Leccino. *Journal of Agricultural and Food Chemistry,* 55, 6609-6618. Servili, M., Taticchi, A., Esposto, S., Urbani, S., Selvaggini, R. & Montedoro, G. 2007b. Effect of

olive stoning on the volatile and phenolic composition of virgin olive oil. *Journal of* 

overexpressed in HER-2/neu-positive breast cancer. *Journal of Biological Chemistry,*

J. M. & Martinez-Gonzalez, M. A. 2007. Mediterranean diet inversely associated

virgin olive oil from young trees (Olea europaea L. cv. Arbequina) grown under linear irrigation strategies. *Journal of Agricultural and Food Chemistry,* 49, 5502-5508. Trichopoulou, A., Lagiou, P., Kuper, H. & Trichopoulos, D. 2000. Cancer and Mediterranean dietary traditions. *Cancer Epidemiology, Biomarkers and Prevention,* 9, 869-873. Trichopoulou, A., Orfanos, P., Norat, T., Bueno-De-Mesquita, B., Ocke, M. C., Peeters, P. H.,

et al. 2005. Modified Mediterranean diet and survival: EPIC-elderly prospective

chondrocytes: effects of antiinflammatory compounds. *Osteoarthritis and Cartilage,*

progression in an Alzheimer's mouse model. *Journal of Psychopharmacology*. Vol- 24,

Effect of enzyme treatment during mechanical extraction of olive oil on phenolic compounds and polysaccharides. *Journal of Agricultural and Food Chemistry,* 49,

Phenolic profiles of Portuguese olive fruits (Olea europaea L.): Influences of

Tung, J., Venta, P. & Caron, J. 2002. Inducible nitric oxide expression in equine articular

Van Dam, D., Coen, K. & De Deyn, P. 2008. Ibuprofen modifies cognitive disease

Vierhuis, E., Servili, M., Baldioli, M., Schols, H. A., Voragen, A. G. & Montedoro, G. F. 2001.

Vinha, A. F., Ferreres, F., Silva, B. M., Valentao, P., Goncalves, A., Pereira, J. A., et al. 2005.

Visioli, F., Bogani, P., Grande, S. & Galli, C. 2005. Mediterranean food and health: building human evidence. *Journal of Physiology and Pharmacology,* 56 Suppl 1, 37-49.

cultivar and geographical origin. *Food Chemistry,* 89, 561-568.

Polyphenols are a wide family of compounds found in fruits and vegetables, wine, tea, cocoa, and extra-virgin olive oil, which exhibit strong antioxidant activity by scavenging different families of Reactive Oxygen Species (ROS). One of the most effective members of the polyphenol family in terms of free radical scavenging is hydroxytyrosol, 2-(3,4 dihydroxyphenyl)ethanol (Fernández-Bolaños et al., 2008), a simple phenol found predominantly in olive tree (*Olea europaea*).

Hydroxytyrosol (HT) can be found in leaves and fruits of olive, extra virgin olive oil and it is specially abundant in olive oil mill wastewaters from where it can be recovered (Fernández-Bolaños et al., 2008; Sabatini, 2010). Hydroxytyrosol is a metabolite of oleuropein (Fig. 1), another major phenolic component of olive products; they both give to extra-virgin olive oil its bitter and pungent taste (Omar, 2010a). Hydroxytyrosol shows a broad spectrum of biological properties due to its strong antioxidant and radical-scavenging properties. More active than antioxidant vitamins and synthetic antioxidants, hydroxytyrosol exerts its antioxidant activity by transforming itself into a catechol quinone (Rietjens, 2007).

Fig. 1. Structures of hydroxytyrosol and oleuropein

### **2. Biological activity of hydroxytyrosol**

Historically, olive tree leaves were used for traditional therapy by ancient civilizations. Extracts from olive tree leaves were found to have a positive effect on hypertension by the

Biological Properties of Hydroxytyrosol and Its Derivatives 377

It has been reported that HT may exert a pro-apoptotic effect by modulating the expression of genes involved in tumor cell proliferation of promyelocytes (HL60 cells) (Fabiani et al., 2006, 2008, 2009, 2011). Moreover, it has been shown that HT inhibits proliferation of human MCF-7 breast cancer cells (Siriani et al., 2010; Bulotta et al. 2011; Bouallagui et al., 2011a), human HT29 colon carcinoma cells (Guichard et al., 2006), human M14 melanoma cells

Pre-treatment of HepG2 cells with hydroxytyrosol prevented cell damage, what could be due to the fact that hydroxytyrosol may prepare the antioxidant defense system of the cell to

Hydroxytyrosol may have critical effects on the formation and maintenance of bone, and could be used as an effective remedy in the treatment of osteoporosis symptoms, as it can stimulate the deposition of calcium and inhibit the formation of multinucleated osteoclasts in a dose-dependent manner. HT also suppressed the bone loss of spongy bone in femurs of

Antimicrobial activity of oleuropein, tyrosol and hydroxytyrosol has been studied *in vitro*

The *in vitro* antimycoplasmal activity of HT has been investigated, concluding that this compound might be considered as an antimicrobial agent for treating human infections caused by bacterial strains or casual agents of intestinal or respiratory tract (Furneri et al., 2004).

It has been shown that polyphenols from olive oil are powerful anti-*Helicobacter Pylori* compounds *in vitro* (Romero et al., 2007), a bacteria linked to a majority of peptic ulcers and

Inflammation and its consequences play a crucial role in the development of atherosclerosis and cardiovascular diseases. Polyphenols have been shown to decrease the production of

The effect of hydroxytyrosol on platelet function has been tested. Hydroxytyrosol was proven to inhibit the chemically induced aggregation, the accumulation of the proaggregant agent thromboxane in human serum, the production of the pro-inflammatory molecules leukotrienes and the activity of arachidonate lipoxygenase (Visioli et al., 2002).

Recently, it has been described that HT-20, an olive oil extract containing about 20% of hydroxytyrosol, inhibits inflammatory swelling and hyperalgesia, and suppresses

Hydroxytyrosol and oleuropein have been identified as a unique class of HIV-1 inhibitors that prevent HIV from entering into the host cell and binding the catalytic site of the HIV-1

inflammatory markers, such as leukotriene B4, in several systems (Biesalski, 2007).

proinflammatory cytokine in a rat inflammation model (Gong et al., 2009).

(D'Angelo et al., 2005) and human PC3 prostate cells (Quiles et al., 2002).

face oxidative stress conditions (Goya et al., 2007, 2010).

against bacteria, viruses and protozoa (Bisignano et al., 1999).

ovariectomized mice (Hagiwara et al., 2011).

**2.3 Osteoporosis** 

**2.4 Antimicrobial activity** 

to some types of gastric cancer.

**2.5 Antiinflammatory activity** 

**2.6 Antiviral activity** 

middle of last century (Scheller, 1955; Perrinjaquet-Moccetti et al. 2008; Susalit et al., 2011), and, since then, the benefits of minor olive components have been extensively investigated (Tripoli et al., 2005).
