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The Antioxidant and Bioactive Potential of Olive Mill Waste

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Karen Attard and Frederick Lia

Submitted: 08 November 2023 Reviewed: 24 November 2023 Published: 14 February 2024

DOI: 10.5772/intechopen.1004127

The Power of Antioxidants - Unleashing Nature's Defense Against Oxidative Stress IntechOpen
The Power of Antioxidants - Unleashing Nature's Defense Again... Edited by Ana Novo Barros

From the Edited Volume

The Power of Antioxidants - Unleashing Nature's Defense Against Oxidative Stress [Working Title]

Dr. Ana Novo Barros and Dr. Ana Cristina Santos Abraão

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Abstract

Olive mill waste (OMW) is a by-product of the olive oil production process that has attracted increasing attention due to its rich composition of bioactive compounds. This chapter explores the extensive and diverse antioxidant and bioactive potential of OMW. OMW is a complex mixture comprising organic compounds, including phenolic compounds, flavonoids, polysaccharides, and various other valuable molecules. These compounds have demonstrated a wide range of applications, including their use as fertilizers, antioxidants, antifungal and antibacterial agents, cytoprotective agents, and stabilizing agents in food preservation. The chapter delves into the types of phenolic compounds found in OMW, providing detailed insights into their structures and functions. Additionally, it discusses the factors affecting the composition of OMW, such as the extraction process and processing conditions. Additionally, the chapter explores the growing interest in the health benefits associated with the consumption of bioactive compounds derived from OMW. These compounds have been linked to potential therapeutic properties, including antioxidant, anti-inflammatory, and anticancer effects. The exploration of OMW’s bioactive potential opens avenues for research and innovation, offering sustainable solutions for both waste management and the development of health-promoting products.

Keywords

  • olive mill waste
  • antioxidants
  • bioactivity
  • olive pomace
  • polyphenols
  • olive mill wastewater

1. Introduction

Olive oil derived from the olive also known as Olea europaea L., is one of the oldest species of domestic trees and the second most important fruit crop cultivated worldwide [1]. The prominence of olive oil in the Mediterranean diet can be known for its nutritional abundance and beneficial health effect, establishing it as a fundamental element of this dietary pattern. In fact, approximately 3 million tons of olive oil are manufactured globally, with 2 million tons of this output originating from the European Union (EU), where the EU holds the distinction of being the leading producer, exporter, and consumer of olive oil worldwide [2]. Notably, the Mediterranean region, encompassing countries like Spain, Italy, Greece, and Portugal, accounts for nearly 99% of the EU’s olive oil production [3, 4, 5, 6].

The milling industry generates substantial waste, known as OMW. In fact, during the production of olive oil it is estimated that an average volume of olive mill wastewater (OMWW), ranging from 0.3 to 1.2 m3/tons of processed olives, and an average quantity of solid residue ranging from 500 to 735 kilograms per ton of processed olives has been reported always depending on the extraction methods used [7, 8, 9, 10]. In 3-phase mills, average freshwater consumptions range from 700 to 1000 L/per ton of olives processed and the generated OMWW is 1200 L/per ton, the highest of all processes. In comparison, the 2 phase mills utilize 100–120 L/per ton of freshwater consumed and 200 L/per ton of OMWW generated [7, 8, 9, 10]. OMWs are considered highly polluting and phytotoxic due to their acidity, high levels of biological oxygen demand (BOD), and chemical oxygen demand (COD) [11]. However, OMWs are also a source of valuable molecules including plant nutrients, flavonoids, polysaccharides, anthocyanins and phenolic compounds [12, 13, 14], with potential industrial applications such as antioxidants, antifungal and antibacterial drugs, cytoprotective agents, fertilizers, and as gelling and stabilizing agents in food preservation [12, 15].

OMWW is characterized as a dark-brown liquid with a pH ranging from 3 to 6 [16, 17]. It is essentially a stable mixture consisting of vegetative water, processed water, residues from olive oil, and fragments of olive pulp. The specific composition of OMWW varies depending on factors such as the extraction method, the olives being processed, and the conditions of processing. Generally, OMWW is primarily composed of water, constituting about 83 to 94% of its weight, along with organic compounds accounting for 4 to 18% of its weight. These organic compounds encompass a range of substances, including sugars, polysaccharides, tannins, organic acids, phenolic compounds, and lipids [17, 18]. However, due to its intricate and variable chemical composition, OMWW poses challenges for direct utilization as a raw material in industrial applications [17, 19].

Olive pomace stands as a prominent by-product generated during the olive oil production process. The chemical composition of olive pomace exhibits considerable variability, influenced by several factors. These factors include the inherent characteristics of the fruit, such as its variety and degree of ripeness, as well as the methods used for oil extraction and the subsequent solvent depletion [20]. This solid residue consists of olive skin, water (~ 25%), pulp, fruit fragments, and traces of oil (4.5–9%) [21]. The primary constituents of olive pomace encompass sugars, mainly polysaccharides, along with proteins, fatty acids such as oleic acid, and various C2-C7 fatty acids, polyalcohols, polyphenols, as well as additional pigments [22]. Additionally, it includes small amounts of organic nitrogen in the form of crude protein and a substantial proportion of dietary fiber [23]. On average, olive pomace consists of approximately 10% hemicellulose, 15% cellulose, and 27% lignin. These parameters categorize this material as a highly lignified and densely walled substrate with very limited digestibility [21].

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2. Classification of bioactive molecules

2.1 Phenolic compounds

Phenolic compounds are a class of secondary metabolites which are naturally occurring in plants, and they are typically distributed non-uniformly at both subcellular and cellular levels. These compounds exist in both soluble and insoluble forms, with the majority of insoluble phenolics being components of the cell walls, while soluble phenolics are typically contained within plant cell vacuoles [24]. Phenolic compounds contain at least one aromatic ring with one hydroxyl group in their structure. There are around 8000 individual plant phenolic compounds, with great structural variability and they can be classified into two main groups namely flavonoids and non-flavonoids [25]. Flavonoids are the most abundant phenolic compounds found in fruit and vegetables as they account for nearly two-thirds of dietary phenolic compounds [26, 27, 28].

With the increase of analytical techniques, the list of olive phenolic compounds is continuously updating. Moreover, in recent years, the potential health benefits associated with the consumption of innovative olive by-product-based preparations have encouraged research efforts to pinpoint the primary compounds known for their favorable physiological effects. In fact, investigations into the phenolic composition of by-products from olive oil production have been conducted, and numerous authors have employed chromatographic methods for their isolation and analysis. These methods include fractionation techniques like solid-phase extraction and LC retention-time identification [29], preparative high-performance liquid chromatography, capillary zone electrophoresis with UV diode array detection [30] and reversed-phase liquid chromatography coupled with mass spectrometry [31].

The major individual biophenols identified in the olive pomace and OMWW were particularly characterized in five classes, namely, simple phenols, phenolic acids, derivatives secoiridoids, flavonoids, and lignans [32]. OMW is known to contain a diverse array of phenolic compounds, each with its own unique set of properties and potential health benefits. Among these compounds, hydroxytyrosol and tyrosol are particularly noteworthy, representing some of the most abundant phenolics in OMW and renowned for their potent antioxidant, antimicrobial and antitumoral properties [33].

Over the last few years, the interest in natural antioxidants, particularly phenolic compounds, in relation to their therapeutic and health beneficial properties has significantly increased. The positive impact of various plant-derived polyphenols on human and mammalian health, including their anticancer properties, has been the subject of numerous studies. Numerous in vitro and in vivo studies have shown that the combination of natural polyphenols with chemotherapeutics can reduce the side effects of chemotherapy, increase the anticancer efficacy, and overcome the chemo or radio resistance of cancer cells [34]. Phenolic compounds extracted from olive oil waste have been shown to exert a possible chemoprotective and anticancer activities in different types of cancer cells [35]: prostate [36], breast cancer [37], colon [38], promyelocytic leukemia [39], melanoma [40], and other cancer cells.

2.2 Phenolic acids

Phenolic acids which were discovered by Friedlieb Ferdinand Runge in 1834 [41], are compounds identified by the presence of a benzene ring, a carboxylic group, and one or more hydroxyl and/or methoxyl groups within their molecular structure [42]. They are one of the main classes of plant phenolic compound and are widely distributed in various plant-based foods, with the highest concentrations often found in seeds, fruit skins, and vegetable leaves [43]. These compounds are typically present in bound forms like amides, esters, or glycosides, and are rarely found in their free form [44]. Notably, phenolic acids possess much higher in vitro antioxidant activity than widely recognized antioxidant vitamins [45, 46]. Additionally, phenolic acids are divided into two sub-groups namely hydroxybenzoic acids and hydroxycinnamic acids [47].

Hydroxycinnamic acids, originating from cinnamic acid, are frequently present in various foods in the form of simple esters with glucose and quinic acid [48]. Among the soluble bound hydroxycinnamic acids, chlorogenic acid is one of the most abundant, resulting from the combination of quinic and caffeic acids. The most common hydroxycinnamic acids found in OMW are typically p-coumaric, ferulic, caffeic, sinapic, vanillic acids and vanillin. [49, 50] Conversely, hydroxybenzoic acids share a common C6-C1 structure and derive from benzoic acid. They are typically found in soluble form, conjugated with organic acids or sugars [48]. Among the frequently found hydroxybenzoic acids in OMW are protocatechuic, syringic, vanillic, gallic and p-hydroxybenzoic acids (Figure 1) [49, 50, 51].

Figure 1.

Major classes of phenolic acids.

Phenolic acids are a key class of dietary polyphenols, renowned for their role as natural antioxidants. Their versatility is evident in their various functions, contributing to plant growth, development, and defense mechanisms. Beyond their primary functions, they also serve as an essential precursor for the production of other significant bioactive compounds, which find extensive applications in therapeutic, cosmetic, and food industries. Most notably, these dietary antioxidants play a crucial role in protecting against the progression and development of pathological conditions triggered by oxidative stress, offering a multifaceted range of benefits [43].

2.3 Phenylethanoids and secoiridoids

Montedoro and collaborators were the first to study the phenylethanoids and secoiridoid class in 1993. They are responsible for the structural characterization of ligstroside and oleuropein aglycones from virgin olive oils [52]. Phenylethanoids are a category of phenolic compounds synthesized by plants, characterized by a C6-C2 carbon skeleton [52]. Secoiridoids on the other hand, are a group of compounds which are usually glycosidically bounded and produce the secondary metabolism of terpenes [53]. These secoiridoids, prevalent in the Oleaceae family, which includes Olea europaea L., are characterized by the presence of elenolic acid in either glycosidic or aglyconic form. Ligstroside and oleuropein stand out as the primary secoiridoids in olive fruits [54]. Both phenylethanoids and secoiridoids are esters formed from 3-hydroxytyrosol or tyrosol (p-hydroxy-phenylethyl alcohol, HPEA) and a secoiridoid corresponding to the glycosidic derivative of a carboxylic acid known as elenolic acid (Figure 2) [55].

Figure 2.

Phenylethanoids and Secoiridoids found in OMW.

2.3.1 Hydroxytyrosol and tyrosol

Hydroxytyrosol and tyrosol are the main compounds found in the phenolic fraction of steam-exploded olive stones and were discovered firstly by Fernandez-Bolanos and collaborators in 1998 [56]. The concentration of tyrosol and hydroxytyrosol, like other phenolic compounds, depends upon various factors inherent to the fruit [57]. These factors encompass genetic elements such as the specific cultivar responsible for production, as well as external factors like agro-pedoclimatic conditions and the degree of fruit ripeness. [58]. Tyrosol, which is also known as 2-(4-hydroxyphenyl)-ethanol, belongs to the phenylethanoids category and exhibits notable cellular antioxidant properties [59]. In fact, it has demonstrated the ability to protect Caco-2 intestinal mucosa from the harmful cytotoxic and apoptotic effects induced by oxidized LDL [60]. Moreover, hydroxytyrosol, also known as 4-(2-hydroxyethyl)-1,2-benzendiol, stands out as an exceptionally potent antioxidant compound within the phenolic compounds derived from the olive tree. Due to its molecular composition, consistent intake of hydroxytyrosol offers numerous benefits, such as serving as an antioxidant, an anti-inflammatory, and a potential anticancer agent [61, 62, 63, 64, 65, 66].

2.3.2 Hydroxytyrosol acetate and hydroxytyrosol glycoside

In 1999, Brenes et al., found hydroxytyrosol derivative, hydroxytyrosol acetate in virgin olive oil [67]. Hydroxytyrosol acetate has been shown to effectively reduce oxidative stress, address mitochondrial dysfunction, and reduce neuronal toxicity [68]. One of the most prevalent forms of dementia among the elderly population is Alzheimer’s diseases, and yet there is currently no established effective treatment. However, a study conducted by Qin et al. reveals that hydroxytyrosol acetate shows a promise in improving cognitive dysfunction associated with Alzheimer’s diseases through a mechanism that depends on estrogen receptor β. In fact, it is evident that HT-ac exhibit a better bioactivity that hydroxytyrosol [69].

Additionally, hydroxytyrosol glucoside belongs to the class of o-glycosyl compounds, a class of organic compounds, where a sugar group is connected through one carbon to another group via O-glycosidic bond [70]. In recent studies, the glucosides of hydroxytyrosol have shown that it can improve the biological activity of the original aglycons on breast cancer cell lines [71].

2.3.3 Oleuropein and ligstroside

OMW consists of a wide range of phenolic compounds, with secoiridoids being the most abundant fraction [72]. De Nino et al. initially detected oleuropein and ligstroside in olive leaves back in 1997, by using an MS [73]. Both compounds are secoiridoid glycosides, showcasing the methyl ester of 3,4-dihydro-2H-pyran5-carboxylic acid, substituting at positions 2, 3, and 4 with hydroxy, carboxymethyl groups, and ethylidene, respectively, as seen in Figure 3 [75]. The anomeric hydroxy group at position 2 is converted into beta-D-glucoside, and the carboxylic acid moiety of the carboxymethyl substituent is converted into the corresponding 3,4-dihydroxyphenethyl ester [75]. Oleuropein and ligstroside, are a prominent constituent in OMW and has shown considerable potential in various health aspects, including cardio protection, anti-inflammatory properties, antioxidants, anti-cancer effects, anti-angiogenic activities, and neuroprotective functions. Therefore, they present a promising therapeutic avenue for addressing a range of human disorders [76, 77].

Figure 3.

A figure shown by Johnson et al. [74], shows the structures of oleuropein, ligstroside and other related hydrolysis products. Oleuropein and ligstroside red bonds are the methyl ester of 3,4-dihydro-2H-pyran5-carboxylic acid, substituting positions 2, 3, and 4 with hydroxy, carboxymethyl groups, and ethylidene.

The aglycone form of ligstroside and oleuropein are the most abundant in secoiridoids [78]. During the maturation process of olives, oleuropein and ligstroside accumulates [79]. As shown in Figure 3, any damages done to the fruit during the ripening process can result in the release of esters [80] which can hydrolyse ligstroside and oleuropein into a range of compounds [81]. Oleuropein aglycone and ligstroside aglycone are formed by hydrolysis. Furthermore, the aglycones can undergo a further ester hydrolysis in order to produce hydroxytyrosol or tyrosol, elenolic acid, and glucose, each of which these compounds can potentially reduce the Folin reagent [82].

2.3.4 Oleocanthal, oleoside and oleacin

Oleuroside, oleocanthal, oleacin and oleoside are all found in olive pomace [51]. Oleoside secoiridoids in the Oleaceae family are typically derived from glucosides of the oleoside variety [83]. These oleosides are characterized by an exocyclic 8,9-olefinic functionality, a combination of elenolic acid and a glucosidic residue [83]. It has been discovered that secoiridoid glycosides of the oleoside type consist of a wide range of pharmacological properties, encompassing antioxidative, antitumor, anti-inflammatory, anti-diabetic, anti-obesity, neuroprotective, and cardiovascular effects [84].

Moreover, oleacin and oleocanthal are among the major phenolic compounds identified in olive oil [85]. These substances represent dialdehydic forms of elenolic acid originating from oleuropein and ligstroside, respectively. Oleacin and oleocanthal have gained significant attention due to their established benefits for health and their impact on sensory properties [86]. In terms of health benefits, they have shown positive effects in the treatment of cardiovascular conditions, specific cancer types, chronic inflammatory ailments, Alzheimer’s disease, and Helicobacter pylori infection [87, 88, 89, 90]. From a sensory perspective, oleacin and oleocanthal are linked to the sharpness and bitterness found in extra virgin olive oil [91].

2.3.5 Nüzhenide and verbascoside

Nüzhenide, a compound discovered by Servili et al. [92], contains at least two glucose moieties in its chemical structure and has been exclusively detected in olive seed [92] and has been found in both olive pomace and OMWW [49]. This secoiridoid compound is known for its potent antioxidant activity [93]. In fact, it has been documented that nüzhenide exhibit anti-osteoporosis effect and numerous other pharmacological benefits, including antioxidant and neuroprotective properties [94, 95].

As for verbascoside, it is a naturally occurring phenylethanoid glycoside that can be found in various medicinal plants. This compound is one of the main hydroxycinnamic found in olives [96]. Notably, the concentration of verbascoside in olive fruit increases as the fruit undergoes maturation. Furthermore, verbascoside exhibits comprehensive pharmacological effects, such as antioxidant and antineoplastic action, and it offers a diverse array of therapeutic benefits for addressing depression [97]. Additionally, it contributes to neuroprotection in the context of Alzheimer’s disease [96].

2.4 Flavonoids

Flavonoids, which were discovered in 1988 by Dr. Albert Szent-Gyorgyi [98], are the largest group of plant phenols which are present in glycosides. This group is represented by different several subclasses such as flavonols (quercitrin, rutin), flavones (apigenin, luteolin and their glucosides) and anthocyanins (cyanidin-3-O-glucosides) as seen in Figure 4 [99]. These compounds are characterized by their large, planar molecular structure, with structural variations arising from modifications involving methoxylation, hydroxylation, glycosylation, and phenylation [99]. Although flavonoids share a common low molecular weight and possess a C6-C3-C6 structure, this designation encompasses a wide range of compounds with various structural variations [100].

Figure 4.

Simple flavonoids present in OMW.

2.4.1 Flavonol

Flavonols, as a subclass, are defined by the presence of a double bond between position 2 and 3 and an oxygen atom at position 4 of the C ring [101]. While they share similarities with flavones, they differ in the presence of hydroxyl group at position 3, making the flavanol skeleton, a 3-hydroxyflavone [101]. Flavonols are mainly represented by glycosides of quercetin, kaempferol, myricetin and isorhamnetin [102]. In fact, quercetin and rutin are the two main compounds identified in OMW [49]. The flavonols found in our dietary intake have the potential to inhibit the initiation, promotion, and progression of cancer by regulating key enzymes and receptors within signal transduction pathways associated with processes like proliferation, inflammation, angiogenesis, apoptosis, metastasis, differentiation and the reversal of multidrug resistance [103].

2.4.2 Flavone

Flavones are characterized by a structure composed of a fused A and C ring, along with a phenyl B ring attached at position 2 of the C ring [104]. A prominent compound in the flavone group is chrysin, which shares the typical flavone structure with hydroxyl groups at positions 5 and 7 of the A ring [105]. Notably, the main flavones identified in OMW are apigenin, apigenin-7-glucoside, luteolin, and luteolin-7-glucoside [49]. Flavones are increasingly recognized as effective anticancer agents due to their inherent antioxidant properties and their capacity to regulate epigenetic targets, particularly histone deacetylases [106].

2.4.3 Anthocyanins

Anthocyanins, a subgroup of flavonoids naturally found in plants, are the pigments responsible for the red, blue, and purple colors [107]. They consist of a basic chemical structure of flavylium cation which links with a hydroxyl and methoxy group, and one or more sugars [102]. The pathway through which anthocyanins enter the bloodstream differs from that of other phenolic compounds. When anthocyanins are consumed, they undergo digestion within the gastrointestinal tract. Subsequently, they are absorbed into the bloodstream and undergo metabolic processes [108]. Most anthocyanins reach the large intestine, where they undergo various transformations influenced by changing physiological conditions [109]. Additionally, anthocyanins may undergo further modifications through interactions with various enzymes in the small intestine before entering the bloodstream [110]. In contrast, the absorption of other phenolic compounds occurs in the small intestine through passive diffusion or transporters [74]. Only 5–10% of these compounds are absorbed in the colon [111]. From the colon, the resulting metabolites are subsequently transported to the liver where phenolic compounds undergo biotransformation in two phases with different enzymatic steps [112]. Once both phases are complete, the metabolites are distributed in the bloodstream with the assistance of plasma proteins such as albumin [113].

The main anthocyanins found in the olive fruit and OMWW are cyanidin, cyanidin-3-glycoside, cyanidin-3-rutinoside, cyanidin-3-caffeyglycoside, cyanidin-3-caffeylrutinoside, delphinidin 3-rhamosylglycoside-7-xyloside [4, 114, 115]. These compounds serve diverse industrial purposes, functioning as components in fertilizers, antioxidants, antifungal and antibacterial medications, cytoprotective agents, and as gelling and stabilizing agents in food preservation [15]. Anthocyanins offer demonstrated health benefits, such as anti-inflammatory and antioxidant properties [116], which help reduce oxidative stress and, consequently, contribute to the prevention of cancer and cardiovascular diseases [117].

2.5 Lignans

Lignans are another group of phenolic compounds which are derived from phenylalanine and consist of two phenylpropane units linked together with β, β-bonds as shown in Figure 5. The most abundant lignans found in OMW are (+) – pinoresinol and (+)-1- acetoxypinoresinol. These were found by Brenes et al. and Owen et al. [118, 119].

Figure 5.

Lignans present in OMW.

2.5.1 (+) – Pinoresinol and (+)-1- acetoxypinoresinol

Pinoresinol exhibits a chemical structure similar to estrogen, categorizing it as a phytoestrogen [120]. Estrogen plays a fundamental role in mammary gland growth and development and has been associated with breast cancer initiation and progression, mainly due to its enhanced binding and activation of estrogen receptor α (Erα) [121]. A study conducted by López-Biedma et al. in 2016, suggests that pinoresinol possesses chemical antioxidant properties, implying its potential therapeutic utility in mitigating breast cancer development. This effect is achieved through the reduction of intracellular oxidative stress and DNA damage in human mammary epithelial cells. Additionally, pinoresinol elevates ROS levels in breast cancer cells upon exposure to H2O2 treatment. Consequently, pinoresinol exerts anti-tumor effects at low concentrations, facilitating cytotoxic, antiproliferative, and pro-oxidant actions in breast cancer cells, irrespective of their estrogen receptor status [120]. Regarding acetoxyinoresinol, it exhibits biological activities, such as its ability to inhibit FASN in human SKBR3 and MCF7 breast cancer cells. Moreover, it reduces HER2 expression and activation in HER2-dependent on the breast cancer cells [122].

2.6 Tocopherols

Tocopherols, a major form of vitamin E, are a group of fat-soluble phenolic compounds. Each tocopherol consists of a chromanol ring and a 16-carbon phytyl chain [123]. Depending on the number and position of methyl groups on the chromanol ring, tocopherols are designated as α, β, δ and γ [123]. α-Tocopherols are trimethylated at the fifth, seventh, and eighth positions of the chromanol ring, β-Tocopherol is dimethylated at the fifth and eighth positions, γ-Tocopherol is dimethylated at the seventh and eighth positions, and δ-Tocopherol is methylated at the 8th position [124]. In a study conducted by Russo et al. in 2020, it was discovered that all four tocopherols were present in both OMW and OMWW [51] Typically, the levels of tocopherols in oil can vary due to various factors, including the year of harvest, climatic conditions, storage duration, extraction methods, soil characteristics, and the spacing between olive trees [125].

Due to their potent antioxidant properties, there is a suggested potential for tocopherols to reduce the risk of cancer [126]. Multiple studies have indicated an association between lower vitamin E nutritional status and an elevated risk of cancer [127, 128]. Among tocopherols, α-Tocopherol is recognized as the most biological active form of tocopherols that makes up the family of vitamin E molecule [129]. Consequently, α-tocopherol has been the most commonly utilized form in studies focusing on cancer prevention. Nevertheless, findings from in vitro and in vivo research conducted by Das Gupta and Suh in 2016 propose that γ-tocopherol and δ-tocopherol might exhibit stronger anticancer properties compared to α-tocopherol (Figure 6) [130].

Figure 6.

Tocopherol structures with the number and position of the methyl groups on the aromatic ring.

2.7 Xanthophylls and carotenoids

Olive pomace is a useful source of carotenoids [131]. Carotenoids are tetraterpene pigments that exhibit yellow, orange, red and purple colors. They are the most widely distributed pigments in the natural world and can be found in photosynthetic bacteria, certain archaea and fungi, algae, plants, and animals [132]. Typically, carotenoids are composed of eight isoprene units, forming a 40-carbon structure [132]. Their fundamental structures usually consist of a polyene chain featuring nine conjugated double bonds, with end groups at both ends of the polyene chain, as illustrated in Figure 7 [133, 134].

Figure 7.

Basic structure of carotenoids.

Carotenoids can be classified into two main categories: carotenes and xanthophylls. In nature, there are about 50 different carotenes, including α-carotene, β-carotene, β, ψ-carotene (γ-carotene), neoxanthin, mutatoxanthin, and lycopene. These carotenes are primarily hydrocarbons [133], and some of them can be found in olive oil [135]. Notably, various compounds have been identified, with β-carotene playing a significant role in protecting plants against photooxidative processes [136]. Carotenes are biologically important to prevent oxidative damage to lipid membranes, and some of them are also precursors of vitamin A. Their intake through nutrition, promotes the reduction of diseases of the skin and eyes as well as the reduction of cardiovascular problems such as oxidation of low-density cholesterol [134].

On the other hand, xanthophylls, such as β-cryptoxanthin, lutein, luteoxanthin, zeaxanthin, antheroxanthin, fucoxanthin, violaxanthin, and peridinin, incorporate oxygen atoms in the form of hydroxy, carbonyl, aldehyde, carboxylic, epoxide, and furanoxide groups within their molecular structures. Some of these xanthophylls can also be found in olive oil [135]. Additionally, certain xanthophylls exist as fatty acid esters, glycosides, sulfates, and as constituents of protein complexes, resulting in a wide range of structural diversity. As of 2018, approximately 800 distinct xanthophylls had been documented in nature (Figure 8) [133].

Figure 8.

Basic carotenoids and xanthophylls found in olive oil and OMW.

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3. Traditional extraction methods

The initial and crucial step in OMW is the extraction process, as it is essential to isolate the specific chemical components from the plant materials to enable further separation and characterization. This process encompasses several key steps, including filtering, freeze-drying and grinding to achieve a homogenous sample. Proper actions must be implemented to ensure that the potential active constituents are not lost, distorted, or degraded during the extraction process from the plant samples [137]. In fact, the addition of sulfites, such as sulfur dioxide, can serve as a potent inhibitor of phenoloxidases, an enzyme responsible for the degradation of phenolic compounds. This can be an effective way to prevent the oxidation of bioactive compounds [138]. Furthermore, the incorporation of natural antioxidants like ascorbic acid (vitamin C) or tocopherol (vitamin E) can protect bioactive compounds from oxidative degradation [139]. Maintaining the pH at an optimal level is also important, since it will prevent the breakdown of bioactive compounds, given that many enzymes are sensitive to pH variations [140]. Additionally, storing OMW at lower temperatures is advisable, as it can retard enzymatic and chemical reactions, thereby contributing to the preservation of bioactive compounds [141].

The selection of a solvent system primarily relies on the specific characteristics of the targeted bioactive compound. Different solvent systems are available to extract the bioactive compound from natural product [142]. Obied et al. found that a water/methanol mixture was the most effective [143], while Allouche et al. identified ethyl acetate as the best solvent for recovering phenolic monomers [144]. Chanioti et al. further expanded on this by introducing natural deep eutectic solvents, with choline chloride and citric acid showing the highest extraction efficiency [145]. Lafka et al. also highlighted the potential of ethanol for extracting phenols, particularly hydroxytyrosol. These studies collectively suggest that a combination of water/methanol, ethyl acetate, and natural deep eutectic solvents may be the most effective solvents for extracting phenolic compounds from olive mill waste [146]. On the other hand, more lipophilic compounds are extracted using dichloromethane or a mixture of dichloromethane and methanol in a 1:1 ratio [142]. This was seen in a study conducted by Cequie-Sanchez et al. where dichloromethane was used as a solvent for lipid extraction [147]. In certain situations, hexane may be utilized for the removal of chlorophyll [142]. Giving that the target compounds may be non-polar to polar and thermally labile, the suitability of the methods of extraction must be considered. Various techniques, including sonification, soxhlet extraction, heating under reflux and others, are commonly employed for the plant sample extraction. Additionally, plant extracts can be prepared by macerating or percolating fresh green plants or dried powdered plant material in water and/or organic solvent systems. [148].

3.1 Advanced extraction processes

Traditional extraction techniques like, digestion [149], percolation [150], maceration [151] and the preparation of decoctions and infusions [152] are being replaced by advanced extraction methods to enhance the efficiency and specificity of extracting bioactive compounds [153]. These advanced approaches employ diverse techniques including microwaves, ultrasound, supercritical fluids, and more [153]. These innovative extraction methods yield final extracts that are notably enriched in desired compounds while minimizing the formation of unwanted byproducts. Furthermore, they are often characterized by their simplicity, speed, eco-friendliness, and full automation, making them an alternative to traditional extraction procedures to meet the rising market demand [154].

3.1.1 Microwave assisted extraction

Microwave-assisted extraction (MAE) has been successfully applied to olive mill waste, particularly in the extraction of valuable compounds such as triterpenoic acids [155], hydroxytyrosol, mannitol, and proteinaceous material [156]. This method has also been used to accelerate the extraction of biophenols from olive leaves, achieving complete extraction in just 8 minutes [157]. Furthermore, the performance of a microwave assisted Soxhlet extractor for olive seeds has been evaluated, with significant reduction in extraction time and labor intensity [158]. These studies collectively demonstrate the potential of MAE in the valorization of olive mill waste, offering a more efficient and sustainable approach to the extraction of valuable compounds.

3.1.2 Pulsed electric field extraction

Pulsed electric field (PEF) processing is an efficient non-thermal food processing technique using short, high voltage pulses. These electrical pulses create pores in the cells of plants, animals, and microorganisms, leading to cell disintegration and the deactivation of microbes [154]. PEF offers several advantages, such as enhancing the extraction of juices, sugars, colorants, and other active compounds, as well as significantly prolonging the shelf life of food products. It accelerates diffusion processes, like the removal of water from plant or animal tissues and the absorption of marinades, spices, and other additives, thus saving valuable time in production [154].

When applied to olive oil production, PEF brings various benefits. It increases oil yield by breaking down the cell walls of olives, making oil extraction easier. This also enhances the quality of the olive oil by increasing nutrient levels, such as polyphenols. Moreover, it improves stability by reducing the amount of free fatty acids that can lead to oil spoilage over time. [159, 160]. The application of pulse electric field (PEF) extraction on olive mill waste has been explored in several studies. Pappas et al. optimized the use of PEF for the recovery of high-value compounds from fresh olive leaves, achieving a significant increase in polyphenol extractability [161]. Yassine et al. also found success in treating olive mill wastewater using electrocoagulation, a process that involves the application of an electric current [162]. In the context of olive oil extraction, Tamborrino et al. and Romanielloa et al. both demonstrated the potential of PEF technology to improve extractability and enhance oil quality. These studies collectively suggest that PEF extraction can be a promising method for valorising olive mill waste [163, 164].

3.1.3 Ultrasonic assisted extraction

The use of ultrasonic assisted extraction (UAE) technology is recommended for the recovery of valuable organic compounds. This method produces sonic waves to create intense shear forces that enhance the extraction process by facilitating mass transfer [165]. This enhancement is achieved through cavitation and streaming, along with an internal convection motion of solutes within the solvent, occurring within the pores of the materials [166]. UAE stands out as an environmentally friendly non-thermal technology. It offers various benefits, including shortened extraction times, reduced energy consumption, and lower solvent usage [167].

Conventional extraction techniques are frequently used when extracting compounds from OMW, with the choice of technique depending on the specific characteristics of the material and the targeted compounds [168]. One commonly used approach is solvent extraction, which involves the use of Generally Recognized as Safe (GRAS) solvents. However, this method has the drawback of extended extraction durations (typically around 48 hours) and the application of high temperatures exceeding 80°C, which can potentially result in the denaturation or degradation of the compounds [169]. To overcome this limitation, ultrasound-assisted extraction (UAE) is an alternative [167]. UAE relies on the cavitation effect, which facilitates the damage of the plant cell walls, making it easier to release bioactive compounds into the solvent [170, 171].

Research has shown that ultrasonic treatment can significantly improve the biogas and methane production from OMW [172, 173]. This is achieved by increasing the solubilization of organic matter in the waste, leading to a higher production of biogas and methane. Additionally, the combination of high-power ultrasound and electro-Fenton processes has been found to be effective in reducing contaminants in OMW, making it more suitable for byproduct utilization [174]. Furthermore, ultrafiltration has been identified as an efficient pretreatment method for OMW, particularly in enhancing the extraction of phenolic compounds and improving the effectiveness of secondary treatment [175]. These findings collectively suggest that ultrasonic treatment, in combination with other methods, can significantly enhance the treatment and utilization of OMW.

3.1.4 Super critical fluid extraction

Supercritical fluid extraction (SFE) is an eco-friendly extraction method that offers a twofold solution: it can purify OMWW and simultaneously isolate high-quality oil from this wastewater [176]. SFE ranks among the most commonly utilized techniques for extracting active compounds. Typically, carbon dioxide (CO2) is commonly used as a supercritical fluid, with extraction conditions maintained above the critical temperature of 31°C and critical pressure of 74 bars. Small adjustments in temperature and pressure above these critical points have a substantial impact on the extraction properties, enhancing the supercritical fluid’s capacity to penetrate and dissolve targeted molecules, particularly lipophilic substances [177]. Dali et al., states that freeze-drying process can also be optimized in order to improve the economic process [175].

Supercritical fluid extraction has proven successful in treating olive mill waste, yielding antioxidant-rich extracts [178]. This method has also been used in the gasification of olive oil mill waste, producing hydrogen-rich gas and removing organic carbon and chemical oxygen demand [179]. Furthermore, supercritical water oxidation has been employed for the treatment of olive oil mill wastewater, achieving high efficiency and total mineralization [180].

This green extraction process allows to preserve the quality of the extracted product. Carbon dioxide is an exceptionally eco-friendly option, as it is non-toxic, non-explosive, and readily available in high purity at a low expense. It can be easily recycled within the process and does not leave any solvent residues in the end-product [181]. Numerous studies and reports have indicated that SFE represents a viable alternative to traditional methods, such as solvent extraction, for extracting high-value natural compounds [182]. In fact, Dali et al., states that supercritical extraction is more advantages compared to the conventional solvent extraction because it is ecofriendly and safer to use [175].

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4. Olive mill waste treatment

Several approaches have been reported in the literature for addressing the treatment and disposal of OMWW, including anaerobic digestion, aerobic fermentation, and composting. However, these methods generally result in the loss or degradation of various functional compounds [183, 184, 185]. Therefore, methods such as the biological and physicochemical treatment of OMW, can also be utilized.

Anaerobic digestion is a promising method for treating olive mill waste, as it can generate energy and reduce the environmental impact of these wastes [186, 187]. However, the process can be inhibited by certain compounds, such as phenols and organic acids, which are present in high concentrations in olive mill waste [188]. To enhance the efficiency of anaerobic digestion, pretreatment methods to remove or modify these inhibitors are necessary. Additionally, the resulting digestate from anaerobic digestion can be further processed through composting to produce a high-quality soil amendment or fertilizer [189].

Aerobic fermentation of OMW has been explored in several studies. Boari et al. and Erguder et al., both found that anaerobic treatment of olive mill waste is feasible, with high removal efficiencies and methane gas production [190, 191]. Tziotzios et al. further demonstrated the potential of aerobic biological treatment, achieving significant removal of phenolic compounds and COD [192]. Benitez et al. proposed an improvement to anaerobic biodegradation through ozonation pretreatment, which led to a significant increase in methane yield. These studies collectively suggest that both anaerobic and aerobic fermentation processes can be effective in treating olive mill waste [193].

4.1 Biological and physiochemical treatment of OMW

The biological treatment of OMW aims to reduce organic matter and inorganic nutrients, necessitating the selection and application of microorganisms. It’s worth noting that the presence of phenolic substances in OMW can inhibit microorganisms [9]. Biological methods can encompass aerobic or anaerobic digestion treatments. However, this process is time-consuming and not commonly used as a valorisation technique, primarily involving the conversion of complex organic matter into simpler molecules like biogas [194, 195]. Moreover, physicochemical treatments for OMW include processes such as dilution, evaporation, sedimentation, filtration, centrifugation, and adsorption [196]. These processes are employed to reduce the organic load and toxicity of OMW to acceptable levels. Dilution is a common pretreatment to reduce the toxicity of OMW. Evaporation and sedimentation, in particular, can concentrate OMW by 70–75%. Further treatment is necessary for both the concentrated residue and the supernatant, in the case of sedimentation. [196].

Numerous biotechnological applications have been developed for the utilization of OMW. One such method is lagooning, which employs a natural purification process to reduce the load rejection in organic matter and polyphenol content existing in the OMW, thus producing treated water meeting the required physicochemical quality standards [197]. Composting is another technique utilized for OMW, primarily aimed at enhancing the physical, chemical, and biological properties of soil. This process centers on the decomposition of organic matter into stable compounds rich in humic substances, making it suitable for use as a fertilizer. Despite environmental restrictions on the lagooning process, OMW can still find application as a fertilizer due to its high organic load and the concentration of soluble nutrients, making it valuable for agriculture [198]. Another way for OMW utilization is as animal feed. However, the high sodium and phenolic compound content in OMW can lead to digestive issues in ruminants [199]. To address this concern, research has focused on reducing phenols through specific processes, such as the Dalmolive process, which decreases phenol content to acceptable levels. Additionally, OMW can be harnessed for biogas production. The anaerobic digestion process relies on the biochemical conversion of organic matter, resulting in the generation of carbon dioxide and methane [200].

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5. Potential nutraceuticals of OMW

Polyphenolic compounds, well-known for their beneficial effects on human health, due to their antioxidant, cardioprotective, anticancer, anti-inflammatory, and antimicrobial properties [201, 202] are nowadays widely recognized as valuable molecules in pharmaceutical and nutraceutical fields [203]. Pharmaceuticals offer immediate relief and treatment for specific medical conditions, whereas nutraceuticals focus on preventive care and overall well-being [204].

Olive polyphenols, including hydroxytyrosol, tyrosol, oleuropein, and verbascoside, have been extensively studied for their pharmacological properties. These compounds have been found to possess antioxidant, anti-inflammatory, cardiovascular, immunomodulatory, gastrointestinal, respiratory, autonomic, central nervous system, antimicrobial, anticancer, and chemopreventive properties [205]. The health benefits of these polyphenols, particularly in the context of the Mediterranean diet, have been well-documented, with a focus on their molecular mechanisms of action [206]. Their potential in the prevention and treatment of chronic diseases, including cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer, has been highlighted [207]. Furthermore, the specific anticancer effects of hydroxytyrosol, including its chemopreventive, cytotoxic, and apoptotic effects, have been explored [208].

In general, whilst polyphenols show a potential as therapeutic agents, they also have limitations that hinder their clinical applications. These include poor stability, bioavailability, and membrane permeability [209]. Despite their potential, their use should be carefully considered due to potential toxic effects [210]. Furthermore, the protective effects of polyphenols in chronic diseases are still not fully understood, and better in vivo and in vitro studies are needed [211]. The low oral bioavailability of polyphenols is a major challenge, and their bioactivity should be re-evaluated based on their metabolites [212]. Various studies have explored the use of nanodelivery systems and encapsulation technologies to enhance the bioavailability of polyphenols [213, 214, 215]. These technologies aim to improve the solubility, stability, and controlled release of polyphenols, thereby increasing their absorption and potential health benefits. Additionally, the design of specific synergistic interactions between polyphenols has been proposed to improve their oral bioavailability [216].

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6. Conclusion

In conclusion, this chapter emphasizes the remarkable antioxidant and bioactive potential concealed within OMW. The rich polyphenolic content, notably hydroxytyrosol and oleocanthal, highlights the valuable compounds present in these residues. As discussed, their diverse health benefits, ranging from antioxidant and anti-inflammatory properties to their potential applications in combating various health conditions, highlighting the importance of realizing the undiscovered capabilities within OMW. This includes avenues such as clinical studies, technological advancements, and sustainable applications of these bioactive compounds, fostering a broader understanding of their capabilities. Additionally, proposing practical real-world applications for these compounds could engage industries seeking novel solutions. Moreover, by exploring innovative and eco-friendly methods for extraction and utilization, we pave the way for a more sustainable and health-conscious approach to managing this waste stream. The chapter’s findings offer a compelling case for the continued investigation and harnessing of OMW as a valuable resource, both in terms of health and sustainability.

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Funding

This research was funded by the Malta Council for Science & Technology and the Scientific Technological Research Council of Turkey (Tubitak) through the MCST-Tubitak 2021 Joint Call for R&I Projects under grant agreement No MCST-TUBITAK-2021-2104 for OPobicell project.

References

  1. 1. Tsagaraki E, Lazarides HN, Petrotos K. Chapter 8 - Olive mill wastewater treatment. In: Utilization of by-Products and Treatment of Waste in the Food Industry. Iceland: Springer; 2006. DOI: 10.1007/978-0-387-35766-9_8
  2. 2. Europea, Cleaner Controlled and Cost-Efficient Olive Oil Production [Internet]. 2005. Available from: https://cordis.europa.eu/article/id/80625-cleaning-olive-oil-mill-waste-products
  3. 3. European Commission. Olive Oil [Internet]. 2020. Available from: https://agriculture.ec.europa.eu/farming/crop-productions-and-plant-based-products/olive-oil_en
  4. 4. Alkhalidi A, Halaweh G, Khawaja MK. Recommendations for olive mills waste treatment in hot and dry climate. Journal of the Saudi Society of Agricultural Sciences. 2023;22(6):361-373. DOI: 10.1016/j.jssas.2023.03.002
  5. 5. Azzam MOJ, Al-Malah KI, Abu-Lail NI. Dynamic post-treatment response of olive mill effluent wastewater using activated carbon. Journal of Environmental Science and Health. Part A, Toxic/Hazardous Substances & Environmental Engineering. 2004;39:269-280. DOI: 10.1081/ESE-120027383
  6. 6. Galanakis CM. Chapter 2 - Olive Mill Waste Recent Advances for Sustainable Management. In: Olive mill waste, Recent Advances for Suitable Management 1st Edition. Greece: Elsevier; 2017
  7. 7. Khdair A, Abu-Rumman G. Sustainable environmental management and valorization options for olive mill byproducts in the Middle East and North Africa (MENA) region. PRO. 2020;8:671. DOI: 10.3390/pr8060671
  8. 8. Khdair IA, Abu-Rumman G. Pollution estimation from olive wastewater in Jordan. Heliyon. 2019;5:e02386. DOI: 10.1016/j.heliyon.2019.e02386
  9. 9. Caputo AC, Scacchia F, Pelagagge PM. Disposal of by-products in olive oil industry: Waste-to-energy solutions. Applied Thermal Engineering. 2003;23:197-214. DOI: 10.1016/S1359-4311(02)00173-4
  10. 10. Obied HK, Allen MS, Bedgood DR, Prenzler PD, Robards K, Stockmann R. Bioactivity and analysis of biophenols recovered from olive mill waste. Journal of Agricultural and Food Chemistry. 2005;53:823-837. DOI: 10.1021/jf048569x
  11. 11. Souilem S, El-Abbassi A, Kiai H, Hafidi A, Sayadi S, Galanakis CM. Olive oil production sector: Environmental effects and sustainability challenges. In: OMW. The Netherlands: Elsevier: Amsterdam; 2017. pp. 1-28. DOI: 10.1016/B978-0-12-805314-0.00001-7
  12. 12. Dermeche S, Nadour M, Larroche C, Moulti-Mati F, Michaud P. OMWs: Biochemical characterizations and valorization strategies. Process Biochemistry. 2013;48:1532-1552. DOI: 10.1016/j.procbio.2013.07.010
  13. 13. Nadour M, Laroche C, Pierre G, Delattre C, Moulti-Mati F, Michaud P. Structural characterization and biological activities of polysaccharides from OMW water. Applied Biochemistry and Biotechnology. 2015;177:431-445. DOI: 10.1007/s12010-015-1753-5
  14. 14. Aggoun M, Arhab R, Cornu A, Portelli J, Barkat M, Graulet B. OMW water microconstituents composition according to olive variety and extraction process. Food Chemistry. 2016;209:72-80. DOI: 10.1016/j.foodchem.2016.04.034
  15. 15. Ochando-Pulido JM, Pimentel- Moral S, Verardo V, Martinez-Ferez A. A focus on advanced physico-chemical processes for OMW water treatment. Separation and Purification Technology. 2017;179:161-174. DOI: 10.1016/j.seppur.2017.02.004
  16. 16. Angelidaki I, Ahring BK, Deng H, Schmidt JE. Anaerobic digestion of olive mill effluents together with swine manure in UASB reactors. Water Science and Technology. 2002;45:213-218. DOI: 10.2166/wst.2002.0334
  17. 17. Tundis R, Conidi C, Loizzo MR, Sicari V, Cassano A. OMW water polyphenol-enriched fractions by integrated membrane process: A promising source of antioxidant. Hypolipidemic and Hypoglycaemic Compounds. Antioxidants. 2020;9:602. DOI: 10.3390/antiox9070602
  18. 18. Ammary BY. Treatment of olive mill wastewater using an anaerobic sequencing batch reactor. Desalination. 2005;177:157-165. DOI: 10.1016/j.desal.2004.12.006
  19. 19. Lafi WK, Shannak B, Al-Shannag M, Al-Anber Z, Al-Hasan M. Treatment of olive mill wastewater by combined advanced oxidation and biodegradation. Separation and Purification Technology. 2009;70:141-146. DOI: 10.1016/j.seppur.2009.09.008
  20. 20. Ferhat R, Laroui S, Zitouni B, Lekbir A, Abdeddaim M, Smaili N, et al. Experimental study of solid waste olive’s mill: Extraction modes optimization and physicochemical characterization. Journal of Natural Product and Plant Resources. 2014;4:16-23
  21. 21. Tada ZMS, Faid IAKIM, Hassani S, Salmaoui S. Caractérisation physico-chimique et microbiologique des grignons d’ olive de 26 huileries traditionnelles de la région de Beni Mellal (Maroc) physicochemical and microbiological characterization of the olive residue of 26 traditional oil mills in Beni. Desalination. 2010;5:4-9
  22. 22. Mateos R, Sarria B, Bravo L. Nutritional and other health properties of olive pomace oil. Critical Reviews in Food Science and Nutrition. 2020;60(20):3506-3521. DOI: 10.1080/10408398.2019.1698005
  23. 23. Varelis P. Food chemistry and analysis. In: Reference Module in Food Science. Amsterdam: Elsevier; 2016. DOI: 10.1016/B978-0-08-100596-5.03341-2
  24. 24. Pridham JB. Oligosaccharides and associated glycosidases in aspen tissues. Biochemistry Journal. 1960;76:13-20. DOI: 10.1042/bj0760013
  25. 25. Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313-7352. DOI: 10.3390/molecules15107313
  26. 26. Burak M, Imen Y. Flavonoids and their antioxidant properties. Turkiye Klin Tip Bil Derg. 1999;19:296-304
  27. 27. Castaneda A, Pacheco-Hernandez L, Paez E, Rodriguez JA, Galan-Vidal GA. Chemical studies of anthocyanins: A review. Food Chemistry. 2009;113:859-871. DOI: 10.1016/j.foodchem.2008.09.001. DOI: 10.1016/j.foodchem.2008.09.001
  28. 28. Lee YK, Yuk DY, Lee JW, Lee SY, Ha TY, Oh KW, et al. Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of β-amyloid generation and memory deficiency. Brain Research. 2009;1250:164-174. DOI: 10.1016/j.brainres.2008.10.012
  29. 29. Bouaziz M, Sayadi S. Isolation and evaluation of antioxidants from leaves of a Tunisian cultivar olive tree. The European Journal of Lipid Science and Technology. 2005;107:497-504. DOI: 10.1002/ejlt.200501166
  30. 30. Pérez-Bonilla M, Salido S, Van Beek TA, Linares-Palomino PJ, Altarejos J, Nogueras M, et al. Isolation and identification of radical scavengers in olive tree (Olea europaea) wood. Journal of Chromatography A. 2006;1112:311-318. DOI: 10.1002/ejlt.200501166
  31. 31. Ammar S, Contreras MDM, Gargouri B, Segura-Carretero A, Bouaziz M. Biosurfactant production by the crude oil degrading Stenotrophomonas sp. B-2: Chemical characterization, biological activities and environmental applications. Environmental Science and Pollution Research. 2007;24:3769-3779. DOI: 10.1007/s11356-016-8064-4
  32. 32. Leouifoundi I, Harnafi H, Zyad A. OMW extracts: Polyphenols content, antioxidant, and antimicrobial activities. Advances in Pharmacological and Pharmaceutical Sciences; 2015;2015:714138. DOI: 10.1155/2015/714138
  33. 33. Posadino AM, Cossu A, Giordo R, Piscopo A, Abdel-Rahman A, Piga A, et al. Antioxidant properties of OMW water polyphenolic extracts on human endothelial and vascular smooth muscle cells. Foods. 2021;10(4):800. DOI: 10.3390/foods10040800
  34. 34. Nurgali RT, Jagoe R, Abalo R. Editorial: Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? Frontiers in Pharmacology. 2018;9:245. DOI: 10.3389/fphar.2018.00245
  35. 35. Menendez A, Vazquez- Martin R, Colomer J, Brunet A, Carrasco-Pancorbo R, GarciaVillalba A, et al. Olive oil’s bitter principle reverses acquired autoresistance to trastuzumab (HerceptinTM) in HER2-overexpressing breast cancer cells. BMC Cancer. 2007;7. DOI: 10.1186/1471-2407-7-80
  36. 36. Zubair A, Bhardwaj A, Ahmad SK, Srivastava MA, Khan GK, Patel S, et al. Hydroxytyrosol induces apoptosis and cell cycle arrest and suppresses multiple oncogenic signaling pathways in prostate cancer cells. Nutrition in Cancer Care. 2017;69:932-942. DOI: 10.1080/01635581.2017.1339818
  37. 37. Calahorra E, Martínez-Lara C, De Dios C, Siles E. Hypoxia modulates the antioxidant effect of hydroxytyrosol in MCF-7 breast cancer cells. PLoS One. 2018;13(9):e0203892. DOI: 10.1371/journal.pone.0203892
  38. 38. Hashim Y, Worthington J, Allsopp P, Ternan NG, Brown EM, McCann MJ, et al. Virgin olive oil phenolics extract inhibit invasion of HT115 human and mammalian colon cancer cells in vitro and in vivo. Food & Function Journal. 2014;5:1513-1519. DOI: 10.1039/C4FO00090K
  39. 39. Fabiani R, Rosignoli P, Bartolomeo AD, Fuccelli R, Servili M, Montedoro GF, et al. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human and mammalian blood mononuclear cells and HL60 cells. The Journal of Nutrition. 2008;138:1411-1416. DOI: 10.1093/jn/138.8.1411
  40. 40. Song DY, Lim JI, Jung HJ, Cho SY, Park GT, Kwon YH, et al. Dietary oleuropein inhibits tumor angiogenesis and lymphangiogenesis in the B16F10 melanoma allograft model: A mechanism for the suppression of high-fat diet-induced solid tumor growth and lymph node metastasis. Oncotarget. 2017;8:32027-32042. DOI: 10.18632/oncotarget.16757
  41. 41. Runge FF. Ueber einige Produkte der Steinkohlendestillation. Annalen der Physik und Chemie. 1834;31:65-78. DOI: 10.1002/andp.18341070502
  42. 42. Yang CS, Landau JM, Huang MT, Newmark HL. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annual Review of Nutrition. 2001;21:381-406. DOI: 10.1146/annurev.nutr.21.1.381
  43. 43. Kumar N, Goel N. Phenolic acids: Natural versatile molecules with promising therapeutic applications. Biotechnol Rep (Amst). 2019;20:24:e00370. DOI: 10.1016/j.btre.2019.e00370
  44. 44. Pereira DM, Valentão P, Pereira JA, Andrade PB. Phenolics: From chemistry to biology. Molecules. 2009;14(6):2202-2211. DOI: 10.3390/molecules14062202
  45. 45. Tsao R, Deng Z. Separation procedures for naturally occurring antioxidant hytochemicals. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2004;812:85-99. DOI: 10.1016/j.jchromb.2004.09.028
  46. 46. Shetty K, Wahlqvist ML. A model for the role of the proline-linked pentose-phosphate pathway in phenolic phytochemical bio-synthesis and mechanism of action for human health and environmental applications. Asia Pacific Journal of Clinical Nutrition. 2004;13(1):1-24
  47. 47. Clifford MN. Chlorogenic acids and other cinnamates - nature, occurrence, and dietary burden. Journal of the Science of Food and Agriculture. 1999;79:362-372
  48. 48. Strack D. Phenolic metabolism. In: Dey PM, Harborne JB, editors. Plant Biochemistry. London: Academic Press; 1997. p. 387
  49. 49. Leouifoudi I, Harnafi H, Zyad A. OMW extracts: Polyphenols content, antioxidant, and antimicrobial activities. Advanced Pharmacology Science. 2015;2015:714138. DOI: 10.1155/2015/714138
  50. 50. Cuffaro D, Bertolini A, Berini S, Ricci C, Cascone MG, Danti S, et al. OMW water as source of polyphenols with nutraceutical properties. Nutrients. 2023;15(17):3746. DOI: 10.3390/nu15173746
  51. 51. Russo M, Bonaccorsi IL, Cacciola F, Dugo L, De Gara L, Dugo P, et al. Distribution of bioactives in entire mill chain from the drupe to the oil and wastes. Natural Products. 2020;35(21):4182-4187. DOI: 10.1080/14786419.2020.1752208
  52. 52. Montedoro GF, Servili M, Baldioli M, Miniati E. Simple and hydrolizable phenolic compounds in virgin olive oil. 1. Their extraction, and quantitative and semiquantitative evaluation by HPLC. Journal of Agricultural and Food Chemistry. 1992;40:1571-1576. DOI: 10.1021/jf00021a019
  53. 53. Siler B, Misic D. Biologically active compounds from the genus Centaurium S.L. (Gentianaceae): Current knowledge and future prospects in medicine. Studies in Natural Products Chemistry. 2016:363-397. DOI: 10.1016/B978-0-444-63601-0.00011-9
  54. 54. Marković AK, Torić J, Barbarić M, Brala CJ. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules. 2019;24:2001-2039. DOI: 10.3390/molecules24102001
  55. 55. Preedy VR, Watson RR. Olive Oil in Health and Disease Prevention. 2nd edition. Burlington: Academic Press; 2010
  56. 56. Fernandez-Bolanos J, Flizon B, Brenes M, Guillen R, Heredia A. Hydroxytyrosol and tyrosol as the main compounds found in the phenolic fraction of steam-exploded olive stones. Journal of American Oil Chemists Society. 1998;75:1643-1649. DOI: 10.1007/s11746-998-0106-8
  57. 57. Ghanbari R, Anwar F, Alkharfy KM, Gilani A-H, Saari N. Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.)—A review. International Journal of Molecular Sciences. 2012;13(3):3291-3340. DOI: 10.3390/ijms13033291
  58. 58. González-Rodríguez J, Pérez-Juan P, Luque de Castro MD. Superheated liquids for extraction of solid residues from winemaking processes. Analytical and Bioanalytical Chemistry. 2003;7−8:1190-1195. DOI: 10.1007/s00216-003-2194-5
  59. 59. Karković Marković A, Torić J, Barbarić M, Jakobušić BC. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules. 2019;24(10). DOI: 10.3390/molecules24102001
  60. 60. Giovannini C, Starface E, Modesti D, Coni D, Cantafora A, De Vincenzi M, et al. Tyrosol, the major olive oil biophenol, protects against oxidized-LDL-induced injury in Caco-2 cells. The Journal of Nutrition. 1999;129(7):1269-1277. DOI: 10.1093/jn/129.7.1269
  61. 61. Martinez L, Ros G, Nieto G. Hydroxytyrosol: Health benefits and use as functional ingredient in meat. Medicine. 2018;5(1):13. DOI: 10.3390/medicines5010013
  62. 62. De la Puerta R, Rutierrez VR, Haolt RS. Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochemical Pharmacology. 1999;57:445-449. DOI: 10.1016/s0006-2952(98)00320-7
  63. 63. Di Benedetto R, Varì R, Scazzocchio B, Filesi C, Santangelo C, Giovannini C, et al. Tyrosol, the major extra virgin olive oil compound, restored intracellular antioxidant defences in spite of its weak antioxidative effectiveness. Nutrition, Metabolism and Cardiovascular Diseases. 2006;17:535-545. DOI: 10.1016/j.numecd.2006.03.005
  64. 64. Esterbauer H, Gebiki J, Puhl H, Jurgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radical Biology and Medicine. 1992;13:341-390. DOI: 10.1016/0891-5849(92)90181-f
  65. 65. Berliner JA, Schwartz DS, Territo MC, Andalibi A, Almada L, Lusis AJ, et al. Induction of chemotactic cytokines by minimally oxidized LDL. In: The Chemokines Lindley. Advances in Experimental Medicine and Biology. US: Springer; 1993. pp. 13-18. DOI: 10.1007/978-1-4615-2952-1_2
  66. 66. Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. The FASEB Journal. 1994;8:1279-1284. DOI: 10.1096/fasebj.8.15.8001740
  67. 67. Brenes M, Garcıa A, Garcıa P, Rios JJ, Garrido A. Phenolic compounds in Spanish olive oils. Journal of Agricultural and Food Chemistry. 1999;47:3535-3540. DOI: 10.1021/jf990009o
  68. 68. Granados-Principal S, El-Azem N, Pamplona R, Ramirez-Tortosa C, Pulido-Moran M, Vera-Ramirez L, et al. Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer. Biochemical Pharmacology. 2014;90(1):25-33. DOI: 10.1016/j.bcp.2014.04.001
  69. 69. Qin C, Hu S, Zhang S, Zhao D, Wang Y, Li H, et al. Hydroxytyrosol acetate improves the cognitive function of APP/PS1 transgenic mice in ERβ-dependent manner. Molecular Nutrition and Food Research. 2021;65(3). DOI: 10.1002/mnfr.202000797
  70. 70. Foods. Showing Compound Hydroxytyrosol 1-O-Glucoside (FDB020893). Canadian Institutes of Health Research, Canada Foundation for Innovation, and The Metabolomics Innovation Centre (TMIC), Canada. Available from: https://foodb.ca/compounds/FDB020893
  71. 71. Méndez-Líter JA, Tundidor I, Nieto- Domínguez M, Fernández de Toro B, González Santana A, Isabel de Eugenio L, et al. Transglycosylation products generated by talaromyces amestolkiae GH3 β-glucosidases: Effect of hydroxytyrosol, vanillin and its glucosides on breast cancer cells. Microbial Cell Factories. 2019;18:97. DOI: 10.1186/s12934-019-1147-4
  72. 72. Baccouri O, Guerfel M, Baccouri B, Cerretani L, Bendini A, Lercker G. Chemical composition and oxidative stability of Tunisian monovarietal virgin olive oils with regard to fruit ripening. Food Chemistry. 2008;109:743-754. DOI: 10.1016/j.foodchem.2008.01.034
  73. 73. De Nino A, Lombardo N, Perri E, Procopio A, Raffaelli A, Sindona G. Direct identification of phenolic glucosides from olive leaf extracts by atmospheric pressure ionization tandem mass spectrometry. Journal of Mass Spectrometry. 1997;32:533-541. DOI: 10.1002/(SICI)1096-9888(199705)32:5<533::AID-JMS506>3.0.CO;2-9
  74. 74. Johnson RL, Mitchell AE. Reducing phenolics related to bitterness in table olives. In: Quality of Phenolic Compounds: Occurrence, Health Benefits, and Applications in Food Industry. Hindawi; 2018. DOI: 10.1155/2018/3193185
  75. 75. EMBL-EBI. ChEBI-oleuropein [Internet]. 2017. Available from: https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7747
  76. 76. Sun W, Frost B, Liu J. Oleuropein, unexpected benefits! Oncotarget. 2017;8(11):17409. DOI: 10.18632/oncotarget.15538
  77. 77. De Andres MC, Meiss MS, Sanchez-Hidalgo M, Gonzalez-Benjumea A, Fernandez-Bolanos JG, Alarcon-de-la-Lastra C, et al. Osteoarthritis treatment with a novel nutraceutical acetylated ligstroside aglycone, a chemically modified extra-virgin olive oil polyphenol. Journal of Tissue Engineering. 2020;11:2041731420922701. DOI: 10.1177/2041731420922701
  78. 78. Oliveras-López MJ, Innocenti M, Giaccherini C, Ieri F, Romani A, Mulinacci N. Study of the phenolic composition of Spanish and italian monocultivar extra virgin olive oils: Distribution of lignans, secoiridoidic, simple phenols and flavonoids. Talanta. 2007;73:726-732. DOI: 10.1016/j.talanta.2007.04.045
  79. 79. Mumm R, Hilker M. Direct and indirect chemical defence of pine against folivorous insects. Trends Plant Science. 2006;11(7):351-358. DOI: 10.1016/j.tplants.2006.05.007
  80. 80. Marsilio V, Seghetti L, Iannucci E, Russi F, Lanza B, Felicioni M. Use of a lactic acid bacteria starter culture during green olive (Olea europaea L cv 230 Ascolana tenera) processing. Journal of the Science of Food and Agriculture. 2005;85(7):1084-1090. DOI: 10.1002/jsfa.2066
  81. 81. Jemai H, Bouaziz M, Sayadi S. Phenolic composition, sugar contents and antioxidant activity of Tunisian sweet olive cultivar with regard to fruit ripening. Journal of Agricultural and Food Chemistry. 2009;57:2961-2968. DOI: 10.1021/jf8034176
  82. 82. Gutierrez-Rosales F, Romero MP, Casanovas M, Motilva MJ, Mínguez Mosquera MI. Metabolites involved in oleuropein accumulation and degradation in fruits of Olea europaea L.: Hojiblanca and Arbequina varieties. Journal of Agricultural and Food Chemistry. 2010;58(24):12924-12933. DOI: 10.1021/jf103083u
  83. 83. Omar SH. Oleuropein in olive and its pharmacological effects. Scientia Pharmaceutica. 2010;78(2):133-154. DOI: 10.3797/scipharm.0912-18
  84. 84. Bulotta S, Oliverio M, Russo D, Procopio A. Biological activity of Oleuropein and its derivatives. Natural Products. 2013:3605-3638. DOI: 10.1007/978-3-642-22144-6_156
  85. 85. Obied HK, Prenzler PD, Ryan D, Servili M, Taticchi A, Esposto S, et al. Biosynthesis and biotransformations of phenol-conjugated oleosidic secoiridoids from Olea europaea L. Natural Product Reports. 2008;25(6):1167-1179. DOI: 10.1039/b719736e
  86. 86. Andrews P, Busch JLHC, De Joode T, Groenewegen A, Alexandre H. Sensory properties of virgin olive oil polyphenols: Identification of deacetoxy-ligstroside aglycon as a key contributor to pungency. Journal of Agricultural and Food Chemistry. 2003;51(5):1415-1420. DOI: 10.1021/jf026042j
  87. 87. Romero C, Medina E, Vargas J, Brenes M, De Castro A. In vitro activity of olive oil polyphenols against helicobacter pylori. Journal of Agricultural and Food Chemistry. 2007;55(3):680-686. DOI: 10.1021/jf0630217
  88. 88. Menendez JA, Vazquez- Martin A, Garcia-Villalba R, Carrasco-Pancorbo A, Oliveras-Ferraros C, Fernandez-Gutierrez A, et al. tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial extra-virgin olive oil (EVOO). BMC Cancer. 2008;8:377. DOI: 10.1186/1471-2407-8-377
  89. 89. Lacono A, Gomez R, Sperry J, Conde J, Bianco G, Meli R, et al. Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line. Arthritis and Rheumatism. 2010;62(6):1675-1682. DOI: 10.1002/art.27437
  90. 90. Michel T, Termentzi A, Gikas E, Halabalaki M, Smith AB, Skaltsounis AL. Oleacin and oleocanthal: Two olive oil bioactives in multiple chemical forms. Planta Medica. 2012;78(11):PJ43. DOI: 10.1055/s-0032-1321203
  91. 91. Mateos R, Cert A, Perez Camino MC, Garcia JM. Evaluation of virgin olive oil bitterness by quantification of Secoiridoid derivatives. Journal of the American Oil Chemists’ Society;81(1):71-75. DOI: 10.1007/s11746-004-0859-x
  92. 92. Servili M, Baldioli M, Selvaggini R, Macchioni A, Montedoro G. Phenolic compounds of olive fruit: One- and two-dimensional nuclear magnetic resonance characterization of Nu1 zhenide and its distribution in the constitutive parts of fruit. Journal of Agricultural and Food Chemistry. 1999;47:12-18
  93. 93. Tóth G, Barabás C, Tóth A, Kéry Á, Béni S, Boldizsár I, et al. Characterization of antioxidant phenolics in Syringa vulgaris L. flowers and fruits by HPLC-DAD-ESI-MS. Biomedical Chromatography. 2016;30:923-932. DOI: 10.1002/bmc.3630
  94. 94. Chen Q , Yang L, Zhang G, Wang F. Bioactivity-guided isolation of antiosteoporotic compounds from Ligustrum lucidum. Phytotherapy Research. 2013;27:973-979. DOI: 10.1002/ptr.4820
  95. 95. Silva S, Gomes L, Leitao F, Coelho A, Boas LV. Phenolic compounds and antioxidant activity of Olea europaea L. fruits and leaves. Food Science and Technology International. 2006;12:385-395. DOI: 10.1177/1082013206070166
  96. 96. Chen S, Liu H, Wang S, Jiang H, Gao L, Wang L, et al. The neuroprotection of verbascoside in Alzheimer's disease mediated through mitigation of neuroinflammation via blocking NF-κB-p65 signaling. Nutrients. 2022;14(7):1417. DOI: 10.3390/nu14071417
  97. 97. Zhao Y, Wang S, Pan J, Ma K. Verbascoside: A neuroprotective phenylethanoid glycosides with anti-depressive properties. Phytomedicine. 2023;120:155027. DOI: 10.1016/j.phymed.2023.155027
  98. 98. Sheabar FZ, Neeman I. Separation and concentration of natural antioxidants from the rape of olives. Journal of the American Oil Chemists' Society. 1988;65(6):990-993. DOI: 10.1007/BF02544526
  99. 99. Gorica N. Olive Fruit Phenols in Olive Oil Processing: The Fate and Antioxidant Potential. Nova Gorica: University of Nova Gorica; 2014
  100. 100. Benito M, Manuel Lasa J, Gracia P, Oria R, Abenoza M, Cristina Sánchez-Gimeno A. Evolution of phenols and pigments in extra virgin olive oil from irrigated super-intensive orchard. European Journal of Lipid Science and Technology. 2012;114(5):558-567. DOI: 10.1002/ejlt.201100078
  101. 101. Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. Journal of Nutritional Science. 2016;5:e47. DOI: 10.1017/jns.2016.41
  102. 102. Tazzini N. Flavonols: Definition, structure, food sources’, Tuscany diet. Phytochemicals. 2014;30:301-313
  103. 103. Kubina R, Krzykawski K, Kabala-Dzik A, Wojtczka RD, Chodurek E, Dziedzic A. Fisetin, a potent anticancer flavonol exhibiting cytotoxic activity against neoplastic malignant cells and cancerous conditions: A scoping, comprehensive review. Nutrients;14(13):2604. DOI: 10.3390/nu14132604
  104. 104. Yin KB, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. International Journal of Molecular Science. 2010;11(5):2188-2199. DOI: 10.3390/ijms11052188
  105. 105. Boon Yin K, Ling Chua S, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. International Journal of Molecular Sciences. 2010;11(5):2188-2199
  106. 106. Ganai SA, Sheikh FA, Baba ZA. Plant flavone chrysin as an emerging histone deacetylase inhibitor for prosperous epigenetic-based anticancer therapy. Phytotherapy Research. 2020;35(2):823-834. DOI: 10.1002/ptr.6869
  107. 107. Kong JM, Chia LS, Goh NK, Chia TF, Brouillard R. Analysis and biological activities of anthocyanins. Phytochemistry. 2003;64:923-933. DOI: 10.1016/S0031-9422(03)00438-2
  108. 108. Han F, Yang P, Wang H, Fernandes I, Mateus N, Liu Y. Digestion and absorption of red grape and wine anthocyanins through the gastrointestinal tract. Trends in Food Science and Technology. 2019;83:211-224. DOI: 10.1016/j.tifs.2018.11.05
  109. 109. Kay CD, Pereira-Caro G, Ludwig IA, Clifford MN, Crozier A. Anthocyanins and flavanones are more bioavailable than previously perceived: A review of recent evidence. Annual Review of Food Science and Technology. 2017;8:155-180. DOI: 10.1146/annurev-food-030216-025636
  110. 110. Sandhu AK, Miller MG, Thangthaeng N, Scott TM, Shukitt-Hale B, Edirisinghe I, et al. Metabolic fate of strawberry polyphenols after chronic intake in healthy older adults. Food & Function. 2018;9:96-106. DOI: 10.1039/c7fo01843f
  111. 111. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. The Journal of Nutritional Biochemistry. 2013;24:1415-1422. DOI: 10.1016/j.jnutbio.2013.05.001
  112. 112. Bilal-Hussain M, Hassan S, Waheed M, Javed A, Adil-Farooq M, Tahir A. Bioavailability and metabolic pathway of phenolic compounds. In: Plant Physiological Aspects of Phenolic Compounds. London, UK: IntechOpen; 2019. pp. 1-18. DOI: 10.5772/intechopen.84745
  113. 113. Quiñones M, Miguel M, Aleixandre A. Los polifenoles, compuestos de origen natural con efectos saludables sobre el sistema cardiovascular. Nutrición Hospitalaria. 2012;27:76-89
  114. 114. Foti P, Romeo FV, Russo N, Pino A, Vaccalluzzo A, Caggia C, et al. OMW water as renewable raw materials to generate high added-value ingredients for agro-food industries. Applied. Science. 2021;11(6):7511. DOI: 10.3390/app11167511
  115. 115. Kirirsakis AK, Kiritsakis KA, Tsitsipas CK. A review of the evolution in the research of antioxidants in olives and olive oil during the last four decades. Journal of Food Bioactives. 2020. DOI: 10.31665/JFB.20xx.000xx
  116. 116. Wolniak M. Mechanisms of antioxidative action of anthocyanins. Farmacja Polska;58:931-933
  117. 117. Pool-Zobel B, Bub A, Schröder N, Rechkemmer G. Anthocyanins are potent antioxidants in model systems but do not reduce endogenous oxidative DNA damage in human colon cells. European Journal of Nutrition. 1999;38:227-234. DOI: 10.1007/s003940050065
  118. 118. Brenes M, Garcia A, Garcia P, Garrido A. Rapid and complete extraction of phenols from olive oil and determination by means of a coulometric electrode array system. Journal of Agricultural and Food Chemistry. 2000;48:5178-5183. DOI: 10.1021/jf000686e
  119. 119. Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhader B, Bartsh H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. European Journal of Cancer. 2000;36:1235-1247. DOI: 10.1016/s0959-8049(00)00103-9
  120. 120. Lopez-Biedma A, Sanchez-Quesada C, Beltran G, Delgado-Rodriguez M, Gaforio JJ. Phytoestrogen (+)-pinoresinol exerts antitumor activity in breast cancer cells with different oestrogen receptor statuses. BMC Complementary and Alternative Medicine. 2016;61(1):350. DOI: 10.1186/s12906-016-1233-7
  121. 121. Zhou Z, Qjao JX, Shetty A, Wu G, Huang Y, Davidson NE, et al. Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy. Cellular and Molecular Life Sciences. 2015;71(8):1549. DOI: 10.1007/s00018-013-1376-3
  122. 122. Qusa MH, Abdelwahed KS, Meyer SA, El Sayed KA. Olive oil lignan (+)-acetoxypinoresinol peripheral motor and neuronal protection against the tremorgenic mycotoxin penitrem a toxicity via STAT1 pathway. ACS Chemical Neuroscience. 2020;11:3575-3589. DOI: 10.1021/acschemneuro.0c00458
  123. 123. Constantinou C, Papas A, Constantinou AI. Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs. International Journal of Cancer. 2008;123:739-752
  124. 124. Lu GX, Lee M-J, Liu AB, Yang Z, Lin Y, Shih WJ, et al. δ-Tocopherol is more active than α- or γ-tocopherol in inhibiting lung tumorigenesis in vivo. Cancer Prevention Research (Philadelphia, PA.). 2012;4(3):404-413. DOI: 10.1158/1940-6207.CAPR-10-0130
  125. 125. Rodrigues N, Casal S, Peres AM, et al. Effect of olive trees density on the quality and composition of olive oil from cv. Arbequina. Scientia Horticulturae. 2018;238:222-233. DOI: 10.1016/j.scienta.2018.04.059
  126. 126. Ju J, Picinich SC, Yang Z, Zhao Y, et al. Cancer preventive activities of tocopherols and tocotrienols. Carcinogenesis. 2010;31:533-542
  127. 127. Taylor PR, Qiao Y-L, Abnet CC, Dawsey SM, et al. Prospective study of serum vitamin E levels and esophageal and gastric cancers. Journal of the National Cancer Institute. 2003;95:1414-1416
  128. 128. Mahabir S, Schendel K, Dong YQ , Barrera SL, et al. Dietary -, −, −and -tocopherols in lung cancer risk. International Journal of Cancer. 2008;123:1173-1180
  129. 129. Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, et al. The European perspective on vitamin E: Current knowledge and future research. The American Journal of Clinical Nutrition. 2002;76:703-716
  130. 130. Das Gupta S, Suh N. Tocopherols in cancer: An update. Molecular Nutrition & Food Research. 2016;60:1354-1363. DOI: 10.1002/mnfr.201500847
  131. 131. Roselló-Soto E, Koubaa M, Moubarik A, Lopes RP, Saraiva JA, Boussetta N, et al. Emerging opportunities for the effective valorization of wastes and by-products generated during olive oil production process: Non-conventional methods for the recovery of high-added value compounds. Trends in Food Science and Technology. 2015;45:296-310. DOI: 10.1016/j.tifs.2015.07.003
  132. 132. Maoka T. Carotenoids as natural functional pigments. Journal of Natural Medicines. 2020;74(1):1-16. DOI: 10.1007/s11418-019-01364-x
  133. 133. Britton G, Liaaen- Jensen S, Pfander H. Carotenoids Hand Book. Basel: Birkhäuser; 2004. DOI: 10.1007/978-3-0348-7836-4
  134. 134. Jaswir I, Noviendri D, Rewo FH, Octavianti F. Carotenoids: Source, medical properties and their application in food and nutraceutical industry. Journal of Medicinal Plants Research. 2011;5:7119-7131. DOI: 10.5897/JMPRx11.011
  135. 135. Mateos R, Garcia-Mesa JA. Rapid and quantitative extraction method for the determination of chlorophylls and carotenoids in olive oil by high-performance liquid chromatography. Analytical and Bioanalytical Chemistry. 2006;385:1247-1254. DOI: 10.1007/s00216-006-0472-8
  136. 136. Stahl W, Sies H. Antioxidant activity of carotenoids. Molecular Aspects of Medicine. 2003;24:345-351. DOI: 10.1016/s0098-2997(03)00030-x
  137. 137. Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives. 2001;109:69-75. DOI: 10.2307/3434847
  138. 138. Sayavedra-soto LA, Montgomery MW. Inhibition of polyphenoloxidase by sulfite. Journal of Food Science. 2006;51(65):1531-1536. DOI: 10.1111/j.1365-2621.1986.tb13852.x
  139. 139. Miazek K, Beton K, Sliwinska A, Brozek-Puska B. The effect of β-carotene, tocopherols and ascorbic acid as anti-oxidant molecules on human and animal In vitro/In vivo studies: A review of research design and analytical techniques used. Biomolecules. 2022;12(8):1087. DOI: 10.3390/biom12081087
  140. 140. Robinson PK. Enzymes: Principles and biotechnological applications. Essays in Biochemistry. 2015;59(1):1-41. DOI: 10.1042/bse0590001
  141. 141. El Zbakh H, Abbassi A. Potential use of olive mill wastewater in the preparation of functional beverages: A review. Journal of Functional Foods. 2012;4(1):53-65. DOI: 10.1016/j.jff.2012.01.002
  142. 142. Cos P, Vlietinck AJ, Berghe DV, Maes L. Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’. Journal of Ethnopharmacology. 2006;106:290-302. DOI: 10.1016/j.jep.2006.04.003
  143. 143. Obied H, Allen M, Bedgood D, Prenzler P, Robards K. Investigation of Australian olive mill waste for recovery of biophenols. Journal of Agricultural and Food Chemistry. 2005;53(26):9911-9920. DOI: 10.1021/JF0518352
  144. 144. Allouche N, Fki I, Sayadi S. Toward a high yield recovery of antioxidants and purified hydroxytyrosol from olive mill wastewaters. Journal of Agricultural and Food Chemistry. 2004;52(2):267-273. DOI: 10.1021/JF034944U
  145. 145. Chanioti S, Tzia C. Extraction of phenolic compounds from olive pomace by using natural deep eutectic solvents and innovative extraction techniques. Innovative Food Science & Emerging Technologies. 2018;8:228-239. DOI: 10.1016/J.IFSET.2018.07.001
  146. 146. Lafka T-I, Lazou A, Sinanoglou VJ, Lazos ES. Phenolic and antioxidant potential of olive oil mill wastes. Food Chemistry;125(1):92-98. DOI: 10.1016/j.foodchem.2010.08.041
  147. 147. Cequier-Sanchez E, Rodriguez C, Ravelo AG, Zarate R. Dichloromethane as a solvent for lipid extraction and assessment of lipid classes and fatty acids from samples of different natures. Journal of Agricultural and Food Chemistry. 2008;56(12):4297-4303. DOI: 10.1021/jf073471e
  148. 148. Sasidharan S, Chen Y, Saravanan D, Sundram KM, Yoga LL. Extraction, isolation and characterization of bioactive compounds from Plants' extracts. African Journal of Traditional, Complementary, and Alternative Medicines. 2011;8(1):1-10
  149. 149. Doellinger J, Schneider A, Hoeller M, Lasch P. Sample preparation by easy extraction and digestion (SPEED) - a universal, rapid, and detergent-free protocol for proteomics based on acid extraction. Molecular & Cellular Proteomics. 2020;19(1):209-2022. DOI: 10.1074/mcp.TIR119.001616
  150. 150. Wang W-Y, Qu H-B, Gong X-C. Research progress on percolation extraction process of traditional Chinese medicines. Zhongguo Zhong Yao Za Zhi. 2020;45(5):1039-1046. DOI: 10.19540/j.cnki.cjcmm.20191221.305
  151. 151. Gueboudji Z, Kadi K, Mahmoudi M, Hannachi H, Nagaz K, Addad S, et al. Maceration and liquid-liquid extractions of phenolic compounds and antioxidants from Algerian olive oil mill wastewater. Environmental Science and Pollution Research. 2023;30(2):3432-3439. DOI: 10.1007/s11356-022-22482-2
  152. 152. Daswani PG, Ghadge AA, Brijesh S, Birdi TJ. Preparation of decoction of medicinal plants: A self-help measure? Journal of Alternative and Complementary Medicine. 2011;14(12):1099-1100. DOI: 10.1089/acm.2011.0217
  153. 153. Belwal T, Ezzat SM, Rastrelli L, Bhatt ID, Daglia M, Baldi A, et al. A critical analysis of extraction techniques used for botanicals: Trends, priorities, industrial uses and optimization strategies. Trends in Analytical Chemistry. 2018;100:82-102. DOI: 10.1016/j.trac.2017.12.018
  154. 154. PulseMaster. What is pulsed electric field processing? [Internet]. 2009. Available from: https://www.pulsemaster.us/about-pulsemaster
  155. 155. Özkan G, Karacabey E, Arslan N, Odabaşı N. Optimisation of microwave-assisted extraction of triterpenoic acids from olive mill waste using response surface methodology. Quality Assurance and Safety of Crops & Foods. 2016;9(2):179-185. DOI: 10.3920/QAS2015.0783
  156. 156. Gómez-Cruz I, Contreras M, Romero I, Castro E. Optimization of microwave-assisted water extraction to obtain high value-added compounds from exhausted olive pomace in a biorefinery context. Food. 2022;11(14). DOI: 10.3390/foods11142002
  157. 157. Japón-Luján R, Luque- Rodríguez JM, Luque de Castro MD. Multivariate optimisation of the microwave-assisted extraction of oleuropein and related biophenols from olive leaves. Analytical and Bioanalytical Chemistry. 2006;385:753-759. DOI: 10.1007/S00216-006-0419-0
  158. 158. García-Ayuso LE, Luque de Castro MD. A multivariate study of the performance of a microwave-assisted Soxhlet extractor for olive seeds. Analytica Chimica Acta. 1999;382(3):309-316. DOI: 10.1016/S0003-2670(98)00795-8
  159. 159. Tamborrino A, Urbani S, Servili M, Romaniello R, Perone C, Leone A. Pulsed electric fields for the treatment of olive pastes in the oil extraction process. Applied Sciences. 2020;10(1):114. DOI: 10.3390/app10010114
  160. 160. Leone A, Tamborrino A, Esposto S, Berardi A, Servili M. Investigation on the effects of a pulsed electric field (PEF) continuous system implemented in an industrial olive oil plant. Food. 2022;11(18):2758. DOI: 10.3390/foods11182758
  161. 161. Pappas VM, Lakka A, Palaiogiannis D, Athanasiadis V, Bozinou E, Ntourtoglou G, et al. Optimization of pulsed electric field as standalone “green” extraction procedure for the recovery of high value-added compounds from fresh olive leaves. Antioxidants (Basel). 2021;10(10):1554. DOI: 10.3390/antiox10101554
  162. 162. Yassine W, Akazdam S, Zyade S, Gourich B. Treatment of olive mill wastewater using electrocoagulation process. Journal of Applied Surface and Interfaces. 2018;4(1-3):24-30
  163. 163. Tamborrino A, Urbani S, Servili M, Romaniello R, Perone C, Leone A. Pulsed electric fields for the treatment of olive pastes in the oil extraction process. Applied Sciences. 2019;10(1):114. DOI: 10.3390/app10010114
  164. 164. Romanielloa R, Tamborrinob A, Leonea A. Use of ultrasound and pulsed electric fields technologies applied to the olive oil extraction process. Chemical Engineering Transactions;75:13-18. DOI: 10.3303/CET1975003
  165. 165. Chemat F, Rombaut N, Sicaire AG, Meullemiestre A, Fabiano-Tixier AS, AbertVian M. Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review. Ultrasonics Sonochemistry. 2017;34:540-560. DOI: 10.1016/j.ultsonch.2016.06.035
  166. 166. Allaf T, Tomao V, Ruiz K, Chemat F. Instant controlled pressure drop technology and ultrasound assisted extraction for sequential extraction of essential oil and antioxidants. Ultrasonics Sonochemistry. 2013;20:239-246. DOI: 10.1016/j. ultsonch.2012.05.013
  167. 167. Chemat F, Rombaut N, Meullemiestre A, Turk M, Perino S, Fabiano-Tixier AS, et al. Review of green food processing techniques. Preservation, transformation, and extraction. Innovative Food Science & Emerging Technologies. 2017;41:357-377. DOI: 10.1016/j.ifset.2017.04.016
  168. 168. Skaltsounis AL, Argyropoulou A, Aligiannis N, Xynos N. Recovery of high added value compounds from olive tree products and olive processing byproducts. Olive and Olive Oil Bioactive Constituents. 2015:333-356. DOI: 10.1016/B978-1-63067-041-2.50017-3
  169. 169. Karen A, Halil Oztop M, Lia F. The effect of hydrolysis on the antioxidant activity of OMW. Applied Science. 2022;12(23):12187. DOI: 10.3390/app122312187
  170. 170. Medina-Torres N, Ayora- Talavera T, Espinosa-Andrews H, Sánchez-Contreras A, Pacheco N. Ultrasound assisted extraction for the recovery of phenolic compounds from vegetable sources. Agronomy. 2017;7:47. DOI: 10.3390/agronomy7030047
  171. 171. Patist A, Bates D. Ultrasonic innovations in the food industry: From the laboratory to commercial production. Innovative Food Science and Emerging Technologies. 2008;9:147-154. DOI: 10.1016/j.ifset.2007.07.004
  172. 172. Oz NA, Uzun AC. Ultrasound pretreatment for enhanced biogas production from olive mill wastewater. Ultrasonics Sonochemistry. 2015;22:565-572. DOI: 10.1016/j.ultsonch.2014.04.018
  173. 173. Kheiredine B, Derbal K, Charbit K, Amrani M. Biogas production by an anaerobic co-digestion process from olive mill waste: Effect of ultrasonic pre-treatment. Desalination and Water Treatment. 2022;246:139-145. DOI: 10.5004/dwt.2022.28011
  174. 174. Mostafa H, Iqdiam BM, Abuagela M, Marshall MR, Pullammanappallil P, Goodrich-Schneider R. Treatment of olive mill wastewater using high power ultrasound (HPU) and electro-Fenton (EF) method. Chemical Engineering and Processing - Process Intensification. 2018;131:131-136. DOI: 10.1016/J.CEP.2018.07.015
  175. 175. El-Abbassi A, Kiai H, Raiti J, Hafidi A. Application of ultrafiltration for olive processing wastewaters treatment. Journal of Cleaner Production. 2014;65(15):432-438. DOI: 10.1016/j.jclepro.2013.08.016
  176. 176. Dali I, Aydi A, Stamenic M, Kolsi L, Ghachem K, Zizovic I, et al. Extraction of lyophilized olive mill wastewater using supercritical CO2 processes. Alexandria Engineering Journal. 2022;61:237-246
  177. 177. Sapkale GN, Patil SM, Surwase US, Bhatbhage PK. A review -supercritical fluid extraction. International Journal of Chemical Sciences. 2010;8(2):729-743
  178. 178. Caballero AS, Romero-Garcia JM, Castro E, Cardona CA. Supercritical fluid extraction for enhancing polyphenolic compounds production from olive waste extracts. Journal of Chemical Technology and Biotechnology. 2018;95(2):356-362. DOI: 10.1002/jctb.5907
  179. 179. Casademont P, Cardozo-Filho L, Meurer E, Sánchez-Oneto J, Portela JR. Gasification of olive oil mill waste by supercritical water in a continuous reactor. The Journal of Supercritical Fluids. 2018;142:10-21. DOI: 10.1016/J.SUPFLU.2018.06.001
  180. 180. Rivas R, Gimeno O, Portela JR, De La Ossa EM, Beltrán F. Supercritical water oxidation of olive oil mill wastewater. Industrial and Engineering Chemistry Research. 2001;40(16):3670-3674. DOI: 10.1021/ie000995u
  181. 181. De Lucas A, De La Martinez Ossa E, Rincón J, Blanco M, Gracia I. Supercritical fluid extraction of tocopherol concentrates from olive tree leaves. The Journal of Supercritical Fluids. 2002;22(3):221-228. DOI: 10.1016/S0896-8446(01)00132-2
  182. 182. Rui PFF, Rocha-Santos TAP, Duarte AC. Supercritical fluid extraction of bioactive compounds. Trends in Analytical Chemistry. 2016;76:40-51. DOI: 10.1016/j.trac.2015.11.013
  183. 183. Fiorentino A, Gentili A, Isidori M, Lavorgna M, Parrella A, Temussi F. Olive oil mill wastewater treatment using a chemical and biological approach. Journal of Agricultural and Food Chemistry. 2004;52:5151-5154. DOI: 10.1021/jf049799e
  184. 184. Günay A, Çetin M. Determination of aerobic biodegradation kinetics of olive oil mill wastewater. International Biodeterioration & Biodegradation. 2013;85:237-242. DOI: 10.1016/j.ibiod.2013.07.012
  185. 185. Papadimitriou EK, Chatjipavlidis I, Balis C. Application of composting to OMW water treatment. Environmental Technology. 1997;18:101-107. DOI: 10.1080/09593331808616517
  186. 186. Roig A, Cayuela ML, Sánchez-Monedero MA. An overview on olive mill wastes and their valorisation methods. Waste Management. 2006;26(9):960-969. DOI: 10.1016/J.WASMAN.2005.07.024
  187. 187. Serrano A, Villa-Gómez D, Fermoso FG, Alonso-Fariñas B. Is anaerobic digestion a feasible alternative to the combustion of olive mill solid waste in terms of energy production? A critical review. Biofuels, Bioproducts and Biorefining. 2020;15(1):150-162. DOI: 10.1002/bbb.2159
  188. 188. Hamdi M. Anaerobic digestion of olive mill wastewaters. Process Biochemistry. 1996;31(2):105-110. DOI: 10.1016/0032-9592(95)00035-6
  189. 189. Abu Khayer MD, Chowdhury MB, Akratos CS, Vayenas DV, Pavlou S. Olive mill waste composting: A review. International Biodeterioration & Biodegradation. 2013;85:108-119. DOI: 10.1016/j.ibiod.2013.06.019
  190. 190. Boari G, Brunetti A, Passino R, Rozzi A. Anaerobic digestion of olive oil mill wastewaters. Agricultural Waste. 1984;10(3):161-175. DOI: 10.1016/0141-4607(84)90057-X
  191. 191. Erguder TH, Güven E, Demirer GN. Anaerobic treatment of olive mill wastes in batch reactors. Process Biochemistry. 2000;36(3):243-248. DOI: 10.1016/S0032-9592(00)00205-3
  192. 192. Tziotzios G, Michailakis S, Vayenas DV. Aerobic biological treatment of olive mill wastewater by olive pulp bacteria. International Biodeterioration & Biodegradation. 2007;60(4):209-214. DOI: 10.1016/j.ibiod.2007.03.003
  193. 193. Benitez FJ, Beltran-Heredia J, Torregrosa J, Acero JL. Improvement of the anaerobic biodegradation of olive mill wastewaters by prior ozonation pretreatment. Bioprocess Engineering. 1997;17:169-175. DOI: 10.1007/s004490050371
  194. 194. Rozzi A, Malpei F. Treatment and disposal of olive mill effluents. International Biodeterioration & Biodegradation. 1996;38(3-4):135-144. DOI: 10.1016/S0964-8305(96)00042-X
  195. 195. Beccari M, Bonemazzi F, Majone M, Riccardi C. Interaction between acidogenesis and methanogenesis in the anaerobic treatment of olive oil mill effluents. Water Research. 1996;30(1):183-189. DOI: 10.1016/0043-1354(95)00086-Z
  196. 196. Azzam MOJ. Olive mills wastewater treatment using mixed adsorbents of volcanic tuff, natural clay and charcoal. Journal of Environmental Chemical Engineering. 2018;6(2):2126-2136. DOI: 10.1016/j.jece.2018.03.009
  197. 197. Borja R, Alba J, Mancha A, Martin A, Alonso V, Sánchez E. Comparative effect of different aerobic pretreatments on the kinetics and macroenergetic parameters of anaerobic digestion of olive mill wastewater in continuous mode. Bioprocess Engineering. 1998;18(2):127-134. DOI: 10.1007/s004490050422
  198. 198. Paredes C, Bernal MP, Cegarra J, Roig A. Bio-degradation of olive mill wastewater sludge by its co-composting with agricultural wastes. Bioresource Technology. 2002;85(1):1-8. DOI: 10.1016/S0960-8524(02)00078-0
  199. 199. Hamdi M. Future prospects and constraints of olive mill wastewaters use and treatment: A review. Bioprocess Engineering. 1993;8(5-6):209-214. DOI: 10.1007/bf00369831
  200. 200. Martilotti E. Use of Olive by-Products in Animal Feeding in Italy. Rome, Italy: Division de la Production et de la Santé Animale. FAO; 1983
  201. 201. Fraga CG, Croft KD, Kennedy DO, Tomás-Barberán FA. The effects of polyphenols and other bioactives on human health. Food & Function. 2019;10:514-528. DOI: 10.1039/C8FO01997E
  202. 202. Li AN, Li S, Zhang YJ, Xu XR, Chen YM, Li HB. Resources and biological activities of natural polyphenols. Nutrients. 2014;6:6020-6047. DOI: 10.3390/nu6126020
  203. 203. Smiljković M, Dias MI, Stojković D, Barros L, Bukvički D, Ferreira ICFR, et al. Characterization of phenolic compounds in tincture of edible Nepeta nuda: Development of antimicrobial mouthwash. Food & Function. 2018;9:5417-5425. DOI: 10.1039/C8FO01466C
  204. 204. Larian B. Exploring the differences between pharmaceutical vs nutraceutical supplements. 2023. Available from: https://www.mdbiowellness.com/blogs/doctors-desk/exploring-the-differences-between-pharmaceutical-vs-nutraceutical-supplements#:~:text=Pharmaceuticals% 20provide% 20immediate%20relief% 20andcare%20and%20overall%20well-being
  205. 205. Obied HK, Prenzler PD, Omar SH, Ismael R, Servili M, Esposto S, et al. Pharmacology of olive biophenols. Advances in Molecular Toxicology. 2012;6:195-242. DOI: 10.1016/B978-0-444-59389-4.00006-9
  206. 206. Crespo MC, Tomé-Carneiro J, Dávalos A, Visioli F. Pharma-nutritional properties of olive oil phenols. Transfer of new findings to human nutrition. Food. 2018;7(6):90. DOI: 10.3390/foods7060090
  207. 207. Bucciantini M, Leri M, Nardiello P, Casamenti F, Stefani M. Olive polyphenols: Antioxidant and anti-inflammatory properties. Antioxidants. 2021;10(7):1044. DOI: 10.3390/antiox10071044
  208. 208. Nan J, Ververis K, Bollu S, Rodd AL, Swarup O, Karagiannis T. Biological effects of the olive polyphenol, hydroxytyrosol: An extra view from genome-wide transcriptome analysis. Hellenic Journal of Nuclear Medicine. 2014;1:62-9
  209. 209. Oliver S, Vittorio O, Cirillo G, Boyer C. Enhancing the therapeutic effects of polyphenols with macromolecules. Polymer Chemistry. 2016;7:1529-1544. DOI: 10.1039/C5PY01912E
  210. 210. Miranda AR, Albrecht C, Cortez MV, Soria EA. Pharmacology and toxicology of polyphenols with potential as neurotropic agents in non-communicable diseases. Current Drug Targets. 2018;19(2):97-110. DOI: 10.2174/1389450117666 161220152336
  211. 211. Del Rio D, Rodriguez-Mateos A, Spencer J, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxidants and Redox Signaling. 2013;18(14):1818-1892. DOI: 10.1089/ars.2012.4581
  212. 212. Teng H, Chen L. Polyphenols and bioavailability: An update. Critical Reviews in Food Science and Nutrition. 2019;59(13):2040-2051. DOI: 10.1080/10408398.2018.1437023
  213. 213. Aguirre A, Borneo R. Improving bioavailability of polyphenols using nanodelivery systems based on food polymers. Polyphenols in Plants. 2019:59-65. DOI: 10.1016/B978-0-12-813768-0.00004-9
  214. 214. Vivekanandhan DK, Verma P, Singh S. Emerging technologies for improving bioavailability of polyphenols. Current Nutrition & Food Science. 2016;12(1):12-22. DOI: 10.2174/15734013116 66151015213704
  215. 215. Hu B, Liu X, Zhang C, Zeng X. Food macromolecule based nanodelivery systems for enhancing the bioavailability of polyphenols. Journal of Food and Drug Analysis. 2017;25(1):3-15. DOI: 10.1016/j.jfda. 2016.11.004
  216. 216. Scheepens A, Tan K, Paxton JW. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes & Nutrition. 2009;5:75-87. DOI: 10.1007/s12263-009-0148-z

Written By

Karen Attard and Frederick Lia

Submitted: 08 November 2023 Reviewed: 24 November 2023 Published: 14 February 2024

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