**1. Introduction**

Herbal medicine is commonly used to treat skin disorders, and the ethnobotanical remedies are developed in different regions, based on local plants. In particular, two different systems, Ayurvedic herbs, estabilished in India, and the traditional Chinese medicine, which uses the combination of different herbs, are known. In the occidental world, the use of herbal medicine is relative to purified extracts, often substituted for synthetic chemical drugs. In the last years, we assisted an intense return, in the occidental world, to herbal medicine, probably because we are living in the green revolution [1]. The use of vegetable raw materials in the preparation

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of products for local application on the skin dates back to ancient times. The term phytocosmetics, from Greek *kosmesis*, which means adorn, and *phytos*, which means plant, is used to indicate the predominant and preferential use of botanical derivatives in cosmetic products. The vegetable field is an inexhaustible source of raw materials that, transformed by various processes, find many applications, both as functional substances and as excipients of the products. Contrary to some 50 years ago, when the cosmetic use of medicinal herbs was largely based on the mere observation of the traditional use, today, numerous scientific studies on the properties of plant-based drugs, as well as advanced knowledge on technical-scientific ones that allow to extract the active principles contained in the plants, are available. The herbal phytonutrient offers an enormous amount and heterogeneity of substances, which, by means of various extracellular processes, give rise to extracts with various functional applications. The active constituents of plants are in fact represented by a complex mixture of substances of different chemical nature (tannins, pectins, saponins, flavonoids, essences, fixed oils, etc.) whose concentration in the extract is essentially linked to the particular extraction process. The most widely used vegetable extracts are glycolic extracts, hydroalcoholic extracts, distilled water, dried extracts, oily extracts, essential oils, and vegetable oils. Vegetable oils are obtained by cold squeezing of plant drugs whose active ingredients are characterized by oily texture. The oil is predominantly made up of polyunsaturated fatty acids rich in triglycerides and also contains antioxidant substances, liposoluble vitamins, and the so-called insaponifiable fraction, a complex mixture of substances of extreme interest both from the dermatological and cosmetic field. Olive oil, coconut oil, wheat germ oil, borage oil, and almond oil are the main types of vegetable oils used in cosmetics. Compared to other types of oily ingredients, the advantage of using vegetable oils in cosmetics and cosmeceuticals lies primarily in their particular lipid composition, which is very close to the structure and function of that of the physiologic sebum present in the interstices and the surface of the corneal layer of the epidermis. The very high affinity to the skin sebum gives them an excellent ability to restore the physiological skin barrier by means of a protective, filmogenic, and emollient action. In this chapter, we describe the advantageous effects of ozonated olive oil in the treatment of skin disorders; in fact, olive oil is considered one of the most excellent foods for diet, but it has antiinflammatory action, so it is used for skin disease. In the chapter, we report information about the safety and mechanism of action on microorganism and on wound healing.

olives to cure mental illness and wraps to heal ulcers. During the Middle Ages and during the Renaissance, olive oil was used to cure gynecological infections and was considered useful in

Powerful Properties of Ozonated Extra Virgin Olive Oil http://dx.doi.org/10.5772/intechopen.73211 231

Virgin olive oil has been and still is the subject of numerous studies that have attributed great properties to it, both in the field of health and in cosmetology. Various epidemiological studies have shown that the incidence of inflammatory, cardiovascular, and tumor illnesses is generally lower in Mediterranean European countries (such as Greece, Italy, and Spain) than in other western and northern countries [4]. This can be attributed to the high consumption of olive oil in the Mediterranean diet, which contributes to the daily requirement of vitamin E, essential fatty acids, and specific antioxidants, particularly represented by phenolic compounds and tocopherols. In addition, antioxidants have a primary role in resistance to oxidation and hence in the stability of olive oil and have been shown to exert numerous beneficial effects on the human body. The antioxidants' protective effect is mainly due to their ability to inhibit the action of oxygen free radicals, indicated by the acronym ROSs [5]. ROSs are highly reactive species represented by atoms or molecules with one or more electrons being dissipated, capable of generating the so-called oxidative stress. When the organism is subject to an increase in oxidative stress, an increase of F2-isoprostanes (IsoPs) in plasma levels and of urinary excretion is observed. IsoPs are a type of novel compound, structurally similar to prostaglandins, biosynthesized *in vivo* from the free radical–catalyzed peroxidation of arachidonate independent of the cyclooxygenases (COX) [6]. Oxidative stress seems to be the main reason for many chronic and degenerative diseases and skin aging. More specifically, ROSs induce (i) DNA mutations and protein alterations that are the basis of carcinogenesis [7]; (ii) oxidation of low density lipoproteins (LDL) involved in the formation of atherosclerotic plaques [8]; (iii) the onset of chronic intestinal inflammatory diseases, such as Crohn's disease [9]; (iv) probable onset of neurodegenerative diseases, such as Parkinson's disease [10]; and (v) cellular aging, by lipid peroxidation of the membranes, which become more permeable and less effective. All this evidence allows us to understand the importance of antioxidants, even from exogenous sources such as diet. The beneficial effects, and in particular the antitumor activity, of olive oil on human health are attributed to the high content of phenolic substances with high antioxidant power [11]. Phenolic compounds, in synergy with α-tocopherol and coenzyme Q, protect cells from oxidative damage by contrasting the toxic effects of ROS [12]. Through various epidemiological studies, the correlation between the consumption of virgin olive oil and the risk of onset of certain types of cancer has been demonstrated, such as breast [13], lung [14], colon [15], ovary [16], pancreas [17], and prostate cancer [18]. It has been shown that among the phenolic compounds, one of the most biologically active is hydroxytyrosol (3,4-DHPEA) that is able to inhibit the 5-lipoxygenase enzyme, by reducing the production of leukotriene B4 in the leukocytes, originating from the metabolism of the eicosanoids [19]. In addition, hydroxytyrosol is able to inhibit *in vitro* the oxidation of LDL [20] and *in vivo* [21] the aggregation of platelets [22]. Some experimental studies have also shown that the phenolic extract of virgin olive oil and two isolated compounds, the dialdehyde form of hydroxytyrosol (3,4-DHPEA-EDA) and thiol (p-HPEA-EDA), are able to inhibit uncontrolled cellular

the treatment of heart disease, fever, and hypertension.

*1.1.1. Beneficial effects of olive oil: health properties*

#### **1.1. Olive oil**

Olive oil consists of glycerides, such as oleic, arachidic, palmitic, linoleic, and stearic acids, and of phenolic compounds. It is very important in the culinary use, but it has important applications in cosmetic and pharmaceutical fields. The olive tree *Olea europaea* is a common feature of the Mediterranean landscape, with the olive fruit and olive oil being the basic elements in the nutrition of civilizations around the Mediterranean basin for millennia. The principal reason is due to the tree's climatic requirements, which are found in limited areas of the earth's surface [2]. This longevous tree integrates and identifies economically, socially, and culturally with the inhabitants of this land and determines its rural landscape [3]. Even olive leaves have been used in popular medicine. The therapeutic and health properties of olive oil have been known for millennia so much that Hippocrates advised the juice of fresh olives to cure mental illness and wraps to heal ulcers. During the Middle Ages and during the Renaissance, olive oil was used to cure gynecological infections and was considered useful in the treatment of heart disease, fever, and hypertension.

#### *1.1.1. Beneficial effects of olive oil: health properties*

of products for local application on the skin dates back to ancient times. The term phytocosmetics, from Greek *kosmesis*, which means adorn, and *phytos*, which means plant, is used to indicate the predominant and preferential use of botanical derivatives in cosmetic products. The vegetable field is an inexhaustible source of raw materials that, transformed by various processes, find many applications, both as functional substances and as excipients of the products. Contrary to some 50 years ago, when the cosmetic use of medicinal herbs was largely based on the mere observation of the traditional use, today, numerous scientific studies on the properties of plant-based drugs, as well as advanced knowledge on technical-scientific ones that allow to extract the active principles contained in the plants, are available. The herbal phytonutrient offers an enormous amount and heterogeneity of substances, which, by means of various extracellular processes, give rise to extracts with various functional applications. The active constituents of plants are in fact represented by a complex mixture of substances of different chemical nature (tannins, pectins, saponins, flavonoids, essences, fixed oils, etc.) whose concentration in the extract is essentially linked to the particular extraction process. The most widely used vegetable extracts are glycolic extracts, hydroalcoholic extracts, distilled water, dried extracts, oily extracts, essential oils, and vegetable oils. Vegetable oils are obtained by cold squeezing of plant drugs whose active ingredients are characterized by oily texture. The oil is predominantly made up of polyunsaturated fatty acids rich in triglycerides and also contains antioxidant substances, liposoluble vitamins, and the so-called insaponifiable fraction, a complex mixture of substances of extreme interest both from the dermatological and cosmetic field. Olive oil, coconut oil, wheat germ oil, borage oil, and almond oil are the main types of vegetable oils used in cosmetics. Compared to other types of oily ingredients, the advantage of using vegetable oils in cosmetics and cosmeceuticals lies primarily in their particular lipid composition, which is very close to the structure and function of that of the physiologic sebum present in the interstices and the surface of the corneal layer of the epidermis. The very high affinity to the skin sebum gives them an excellent ability to restore the physiological skin barrier by means of a protective, filmogenic, and emollient action. In this chapter, we describe the advantageous effects of ozonated olive oil in the treatment of skin disorders; in fact, olive oil is considered one of the most excellent foods for diet, but it has antiinflammatory action, so it is used for skin disease. In the chapter, we report information about

the safety and mechanism of action on microorganism and on wound healing.

Olive oil consists of glycerides, such as oleic, arachidic, palmitic, linoleic, and stearic acids, and of phenolic compounds. It is very important in the culinary use, but it has important applications in cosmetic and pharmaceutical fields. The olive tree *Olea europaea* is a common feature of the Mediterranean landscape, with the olive fruit and olive oil being the basic elements in the nutrition of civilizations around the Mediterranean basin for millennia. The principal reason is due to the tree's climatic requirements, which are found in limited areas of the earth's surface [2]. This longevous tree integrates and identifies economically, socially, and culturally with the inhabitants of this land and determines its rural landscape [3]. Even olive leaves have been used in popular medicine. The therapeutic and health properties of olive oil have been known for millennia so much that Hippocrates advised the juice of fresh

**1.1. Olive oil**

230 Herbal Medicine

Virgin olive oil has been and still is the subject of numerous studies that have attributed great properties to it, both in the field of health and in cosmetology. Various epidemiological studies have shown that the incidence of inflammatory, cardiovascular, and tumor illnesses is generally lower in Mediterranean European countries (such as Greece, Italy, and Spain) than in other western and northern countries [4]. This can be attributed to the high consumption of olive oil in the Mediterranean diet, which contributes to the daily requirement of vitamin E, essential fatty acids, and specific antioxidants, particularly represented by phenolic compounds and tocopherols. In addition, antioxidants have a primary role in resistance to oxidation and hence in the stability of olive oil and have been shown to exert numerous beneficial effects on the human body. The antioxidants' protective effect is mainly due to their ability to inhibit the action of oxygen free radicals, indicated by the acronym ROSs [5]. ROSs are highly reactive species represented by atoms or molecules with one or more electrons being dissipated, capable of generating the so-called oxidative stress. When the organism is subject to an increase in oxidative stress, an increase of F2-isoprostanes (IsoPs) in plasma levels and of urinary excretion is observed. IsoPs are a type of novel compound, structurally similar to prostaglandins, biosynthesized *in vivo* from the free radical–catalyzed peroxidation of arachidonate independent of the cyclooxygenases (COX) [6]. Oxidative stress seems to be the main reason for many chronic and degenerative diseases and skin aging. More specifically, ROSs induce (i) DNA mutations and protein alterations that are the basis of carcinogenesis [7]; (ii) oxidation of low density lipoproteins (LDL) involved in the formation of atherosclerotic plaques [8]; (iii) the onset of chronic intestinal inflammatory diseases, such as Crohn's disease [9]; (iv) probable onset of neurodegenerative diseases, such as Parkinson's disease [10]; and (v) cellular aging, by lipid peroxidation of the membranes, which become more permeable and less effective. All this evidence allows us to understand the importance of antioxidants, even from exogenous sources such as diet. The beneficial effects, and in particular the antitumor activity, of olive oil on human health are attributed to the high content of phenolic substances with high antioxidant power [11]. Phenolic compounds, in synergy with α-tocopherol and coenzyme Q, protect cells from oxidative damage by contrasting the toxic effects of ROS [12]. Through various epidemiological studies, the correlation between the consumption of virgin olive oil and the risk of onset of certain types of cancer has been demonstrated, such as breast [13], lung [14], colon [15], ovary [16], pancreas [17], and prostate cancer [18]. It has been shown that among the phenolic compounds, one of the most biologically active is hydroxytyrosol (3,4-DHPEA) that is able to inhibit the 5-lipoxygenase enzyme, by reducing the production of leukotriene B4 in the leukocytes, originating from the metabolism of the eicosanoids [19]. In addition, hydroxytyrosol is able to inhibit *in vitro* the oxidation of LDL [20] and *in vivo* [21] the aggregation of platelets [22]. Some experimental studies have also shown that the phenolic extract of virgin olive oil and two isolated compounds, the dialdehyde form of hydroxytyrosol (3,4-DHPEA-EDA) and thiol (p-HPEA-EDA), are able to inhibit uncontrolled cellular proliferation by blocking the cell cycle at G0/G1 and to induce apoptosis in some lines of cancer cells, as demonstrated for HL60 cells of promyelocytic human leukemia [23, 24]. However, compounds with greater biological activity are those containing the ortho-diphenol residues; it has been shown that 3,4-DHPEA and 3,4-DHPEA-EDA are more effective than p-HPEA and p-HPEA-EDA in protecting DNA from damage caused by oxidation [25]. In an *in vitro* study, by examining different virgin olive oil extracts, a chemoprotective effect was demonstrated on HL60 cell lines in relation to their composition but not to the total content of phenolic substances [26]. ROS production is also closely related to inflammatory processes in which the cyclooxygenase enzymes (COX-1 and COX-2), belonging to the oxidoreductase class, catalyze the conversion of arachidonic acid into prostaglandins. The p-HPEA-EDA, also called oleocanthal, has the ability to inhibit the activity of such enzymes and has a pharmacological effect similar to that of ibuprofen, which belongs to the class of nonsteroidal anti-inflammatory drugs [27]. It has also been shown that the consumption of olive oil may improve blood pressure regulation and cholesterol content in the blood; these events, together with the inhibition of platelet aggregation and the reduction of LDL oxidation, are important to prevent the onset of atherosclerotic plaques and, in general, cardiovascular pathologies [28, 29]. Olive oil also contains many monounsaturated fatty acids, including oleic acid, which is a key component of cellular membranes and can progressively replace polyunsaturated fatty acids. Membranes rich in monounsaturated fatty acids are more fluid and less subject to lipid peroxidation [30]. Some studies have also shown that regular intake of this food may result in a reduction in the risk of developing diabetes [31]. The therapeutic properties of olive oil include a laxative effect and stimulation of biliary function [32]. Finally, some studies on animal models have shown that the intake of olive oil can help to counteract the damage caused by epidermal ultraviolet radiation [33].

topical formulations used in the treatment of inflammatory and mycotic skin diseases [40]. The unsaponifiable fraction is rich in numerous active ingredients with sebum-regulating and moisturizing properties, as well as emollients; it can be a component of cosmetic products (in the form of creams, balms, gels, etc.) for the treatment of delicate, dry, and cracked skin. In fact, the unsaponifiable fraction is very useful in the case of particularly vulnerable skin, such as that of infants and children, or in the case of xerotic skin, such as that of the elderly. Skin hydration is above all important in the neonatal period and especially in premature infants: some clinical trials have been conducted to highlight the beneficial effects of emollient topical treatment [41, 42]. Furthermore, the unsaponifiable fraction exerts a good photoprotective effect on ultraviolet exposed skin: various studies have shown that the application of olive oil may reduce the incidence of skin epithelial tumors on UV-B–exposed mice compared to a control group [43, 44]. The unsaponifiable fraction can also be an additive in makeup products with the purpose of making them easier to apply, softer, and smoother. Butter contains high quantities of squalene (which is the most important constituent of sebum), waxes, and esters that guarantee high penetration of the skin. Butter is ideal for massages or as a vehicle for other active ingredients used in skin care. It acts also as an emollient and moisturizing agent, promoting skin elasticity and preventing the onset of wrinkles. Finally, it can be used as an additive in photoprotective products or in skin hygiene products due to its ability to

Powerful Properties of Ozonated Extra Virgin Olive Oil http://dx.doi.org/10.5772/intechopen.73211 233

An interesting and powerful way to use extra virgin olive oil is with ozone. The process of ozonization allows the properties of ozone gas to be combined with those of olive oil; the result is a peerless compound. Since ancient times, ozone has also been used in a large num-

Ozone is an oxygen derivative and is known primarily for its ecological role in the Earth's balance, absorbing most of the ultraviolet radiation from the sun and preventing it from reaching humans in a harmful way. It is an unstable gas that cannot be stored; in fact, it dissolves in very short time. Ozone is totally neutral to the human body, and in fact, it does not (i) modify pH, (ii) irritate skin or mucous membranes, (iii) damage hair or clothing, (iv) interact with drugs, and (v) cause allergic reactions. This molecule has been subjected to countless studies, and in particular, its strong oxidation capacity has been tested in order to underline its disinfectant and sanitizing properties principally applied as a disinfectant of drinking and waste water [45–47]. To this purpose, the dedicated design and construction of equipment for the production of gaseous ozone for air and water purification are increasing. But research into the properties of ozone has yielded promising results in biological applications, thus confirming the ozone activity in stimulating natural cell defenses and increasing their energy availability. Indeed, since ancient times, ozone has also been used in a large number of medical indications [48, 49]. Scientific studies have shown that ozone, while being highly unstable, can be trapped inside vegetable oils. These are composed of triglycerides in which saturated and unsaturated fatty acids are present, which have the ability to retain ozone, thus allowing

neutralize aggressive detergent action.

ber of medical indications [45–49].

**2. Ozone**

#### *1.1.2. Dermatological and cosmetic properties*

In recent years, in a number of fields, including cosmetics, there has been a renewed interest in materials of natural origin, particularly those of vegetable origin. Since ancient times, olive oil has been known not only for its high nutritional power but also for its cosmetic and therapeutic properties [34]. In 1971, Thiers was still pointing to its potential use in the cosmetic sector. To date, olive oil is certainly the most appreciated natural ingredient, alongside jojoba and avocado oils. The topical application of olive oil may be advised for its soothing action and its beneficial effects on eczema, surface wounds, and burns [35, 36]. In particular, the presence of phytosterols and triterpenoid compounds offers revitalizing and soothing properties for the skin. Vitamins E and A have an intense antioxidant action and have the ability to prevent irritation and aging of the skin, to help maintain its softness, smoothness, stability, and elasticity. As a result, in the cosmetic field, olive oil can be used to prevent signs of aging as a soothing emollient for dry skin and to strengthen hair [37]. Indeed, it is very often a component of lotions, lip balms, shampoos, bath oils, and massage oils. From a dermatologic point of view, olive oil has also proven to have antimicrobial activity, *in vitro*, against some positive and negative Gram and various types of fungi, including *Candida* spp. [38]. Some components of olive oil, especially certain aliphatic aldehydes, inhibit elastase activity; this enzyme is involved in the virulence process [39]. Olive oil is an important component of some topical formulations used in the treatment of inflammatory and mycotic skin diseases [40]. The unsaponifiable fraction is rich in numerous active ingredients with sebum-regulating and moisturizing properties, as well as emollients; it can be a component of cosmetic products (in the form of creams, balms, gels, etc.) for the treatment of delicate, dry, and cracked skin. In fact, the unsaponifiable fraction is very useful in the case of particularly vulnerable skin, such as that of infants and children, or in the case of xerotic skin, such as that of the elderly. Skin hydration is above all important in the neonatal period and especially in premature infants: some clinical trials have been conducted to highlight the beneficial effects of emollient topical treatment [41, 42]. Furthermore, the unsaponifiable fraction exerts a good photoprotective effect on ultraviolet exposed skin: various studies have shown that the application of olive oil may reduce the incidence of skin epithelial tumors on UV-B–exposed mice compared to a control group [43, 44]. The unsaponifiable fraction can also be an additive in makeup products with the purpose of making them easier to apply, softer, and smoother. Butter contains high quantities of squalene (which is the most important constituent of sebum), waxes, and esters that guarantee high penetration of the skin. Butter is ideal for massages or as a vehicle for other active ingredients used in skin care. It acts also as an emollient and moisturizing agent, promoting skin elasticity and preventing the onset of wrinkles. Finally, it can be used as an additive in photoprotective products or in skin hygiene products due to its ability to neutralize aggressive detergent action.

An interesting and powerful way to use extra virgin olive oil is with ozone. The process of ozonization allows the properties of ozone gas to be combined with those of olive oil; the result is a peerless compound. Since ancient times, ozone has also been used in a large number of medical indications [45–49].
