1. Introduction

Olive oil is the main product obtained from olives, fruits that come from the Olea europaea L. evergreen trees ^[1]. Olive oil is a characteristic element of the Mediterranean Diet (MD) because of the health-beneficial effects deriving from its chemical composition ^[2][3][4] as well as its appreciable taste and usefulness in flavoring a large variety of foods. In particular, the constituents of both lipidic and unsaponifiable fractions in extra-virgin olive oils (EVOOs) have been demonstrated to be able to reduce oxidative stress by acting on various biomolecules in the body, as also stated by the European Food Safety Authority (EFSA) ^[5].

During the production process of EVOOs, olive milling yields a mixture of olive paste and water. Subsequent malaxation of the olive paste allows for the separation of three phases: (i) the olive oil, (ii) a solid residue, and (iii) the olive mill wastewater (OMW). The last two components are produced in large quantities, and they are considered an agro-industrial waste whose disposal represents an important environmental problem as the plant material is usually subjected to microbial deterioration ^[6][7].

Currently, in the linear economy, agricultural by-products are mainly used as combustion feedstock for biofuels (Figure 1) ^[8][9].

Figure 1. From linear to the circular economy in the olive oil sector.

The most important biomasses are residues from wood working (wood shavings and sawdust) or forestry activities, wastes from farms and agro-business, the organic fraction of municipal solid wastes, and plants deliberately grown for energetic purposes. Similarly, pruning wastes from olive trees are also used as biomass. However, in coherence with the “circular economy” principle, it is important to valorize these waste products containing high levels of secondary metabolites, thus accelerating the implementation of the “Transforming our world: the 2030 Agenda for Sustainable Development” ^[10][11].

Nevertheless, the transition from linear to the circular economy requires a cultural and structural change: a deep revision and innovation of production, distribution, and consumption models ^[12]. Furthermore, from a circular economy perspective, the added value of materials and energy must be maintained for as long as possible over multiple productions and use cycles, representing a new opportunity also for seasonal sectors, such as the EVOOs manufacturing industry.

Olive mill waste, olive pomace (exhausted pulp, kernel, and seeds), and vegetative water are significant by-products of the olive oil-producing countries in the Mediterranean basin, with a high environmental impact if not properly treated. In addition, these wastes are rich in high-value compounds, which can be either used directly after extraction or exploited as ingredients with different applications, e.g., as food supplements, nutraceuticals, cosmeceuticals, and animal feed.

The transition from linear to the circular economy, largely desired from stakeholders in the olive oil sector, requires a multidisciplinary approach that exploits know-how harmonically from different fields (Figure 2).

Figure 2. Extra virgin olive oil’s (EVOO’s) circular economy: overview of an integrated olive tree exploitation.

This transition would also bring an additional value, represented by the possibility that each oil mill can integrate new processes with the pre-existing ones, with the resulting economic advantages, guaranteeing both product diversification and fair income for all stakeholders, who are currently threatened by the increasing oil price trend and the emerging Xylella pandemic.

In this review, we focused our attention on the secondary metabolites contained in waste materials derived from the olive oil production process and their ability to reduce oxidative stress, both in vitro and in vivo. Particular attention has been paid to their potential exploitation in the circular economy by obtaining new high-value ingredients for health-related products (nutraceuticals, pharmaceuticals, and cosmeceuticals).

2. Olea europea L.: Overview on Its Chemical Compounds

The most represented chemical classes in Olea europea L. tree are mainly classified as nonpolar compounds (present in the lipophilic oil fraction, such as squalene, tocopherols, sterols, and triterpenic compounds) and polar phenolic compounds ^[13].

Among the polyphenolic compounds, the most abundant and studied in olives are tyrosol (TY), hydroxytyrosol (HT), oleuropein (OL), oleocanthal, and verbascoside (Figure 3).

Figure 3. Most abundant polyphenols in olives: (a) tyrosol; (b) hydroxytyrosol; (c) oleuropein; (d) oleocanthal; (e) verbascoside.

The secondary metabolites from Olea europea L. have high biological value, and they are present in different concentrations in the various parts of the olive plant (Table 1); as such, many of them are present in the derived EVOOs, but they can also be found in the waste products from the production process.

Table 1. Distribution of the main classes of metabolites in the different parts of the plant Olea europea L. ^{[13][14][15][16][17][18][19][20][21]}.

Seed Oil	Virgin Olive Oil	Skin	Pulp	Wood	Leaves
Phenolic acid/aldehydes	Phenolic acid/aldehydes	Phenolic acid/aldehydes	Phenolic acid/aldehydes	Phenolic acid/aldehydes	Phenolic acid/aldehydes
Tocopherols	Tocopherols		Tocopherols
Sterols	Sterols	Organic acid and coumarins	Organic acid and coumarins	Organic acid and coumarins	Organic acid and coumarins
		Flavonoids	Simple phenols and derivatives	Simple phenols and derivatives	Simple phenols and derivatives
		Lignans	Secoiridoids and derivatives	Secoiridoids and derivatives	Secoiridoids and derivatives
		Fatty acids and derivatives		Flavonoids	Flavonoids
		Pentacyclic triterpenes			Tocopherols

For this reason, all the materials involved in olive oil manufacturing represent a precious reservoir that could supply extracts reusable for health purposes. The most studied secondary metabolites are the polyphenols (or biophenols, as they are often referred to in EVOOs) that represent a group of molecules with one or more phenolic rings ^[14]. These compounds can be defined as nutraceuticals for their biological/pharmacological actions ^[15], mostly derived from their antioxidant properties, that play a protective role against oxidative stress ^[16] and extend the shelf-life of olive oil ^[17].

The antioxidant activity is mainly due to five classes of polyphenols identified as simple phenols, phenolic acids, secoiridoids, flavonoids, and lignans ^[18]. Among these, OL represents the principal biophenol in the olive leaf ^[19], followed by other constituents such as verbascoside, luteolin-7-O-glucoside, apigenin-7-O-glucoside, and TY ^[20]. Their antioxidant activity is even higher than that of antioxidants, such as vitamins E and C ^[21].