**2.1 Phenolic compounds**

Phenolic compounds are assorted as secondary metabolites that have a restricted distribution without any explicit function in general metabolism [10]. On the other hand, primary metabolites including nucleic acid, carbohydrate, protein, lipid and cofactors, are involved in the synthesis of substances that are pivotal for the growth of all organisms [18]. Olive tree polyphenols are present in the plant to combat pathogens inducing bacterial infections and to react to pests and insect injuries [19, 20]. There are a wide variety of phenolic compounds in Olea europaea and its by-products with much more concentration in olive leaves (comparison, 145 mg total phenolics/100 g fresh leaf compared to 110 mg/100 g olive fruit and 23 mg/100 ml extra virgin olive oil) [1, 7, 15]. Another comparison confirms the much more concentration of total polyphenols in olive leaves is relative to the olive oil and fruit; 1350 mg/kg fresh olive leaf versus 232 ± 15 mg/kg of extra virgin olive oil [21, 22]. High content of phenolic compounds in olive leaf excited the interest of many scholars to continue the investigations with animals and humans, and that resulted in realizing the beneficial health effects such as anti-hypertensive effects [23]. Major phenolic compounds extracted from olive leaf are categorised in the following.

#### **Figure 1.**

*The meta-analysis of OLE compared to placebo or no treatment. Outcome: diastolic blood pressure (mmHg).*

*The Effect of Olive Leaf Extract on Systolic and Diastolic Blood Pressure in Adults: A Systemic... DOI: http://dx.doi.org/10.5772/intechopen.102769*

#### **Figure 2.**

*The met-analysis of OLE compared to placebo or no treatment. Outcome: systolic blood pressure (mmHg).*

#### *2.1.1 Olive leaf phenolic compounds categorisation*

Some researchers categorised the phenolic compounds of olive tree in 5 groups: flavones (apigenin-7-glucoside, diosmetin, diosmetin-7-glucoside, luteolin and luteolin-7-glucoside); flavonols (rutin); flavan-3-ols; oleuropeosides (verbascoside and OL) and substituted phenols (vanillin, vanillic acid, caffeic acid, tyrosol and hydroxytyrosol) [24]. Also, some researchers categorised the phenolic compounds of olive leaves into three distinct groups: (1) phenolic acids like vanillic acid, syringic acid, salicylic acid, vanillin, etc. (2) Flavonoids like luteolin, rutin, and apigenin-7-oglucoside, luteolin-7-o-glucoside, etc. (3) Hydroxycinnamates and structurally related compounds like verbascoside, oleoside, ligasterol, oleuropein, etc. [25]. The most abundant phenolic compound identified in olive leaves is oleuropein, followed by hydroxytyrosol, luteolin-7-glucosides, verbascoside, and apigenin-7-glucosides [23]. It has been demonstrated that there are some factors that affect the chemical composition variability of olive leaves, like origin, storage conditions, proportion of branches existing in the extract, weather conditions, moisture content and degree of soil contamination [26, 27]. On the other hand, some processes such as drying and extraction enable us to change nutritional composition of the OLE [28]. Oleuropein, the principal phenolic compound in olive leaf has a significant impact on the reduction of blood pressure due to the potential mechanisms of action with its specific chemical characteristics [2].

#### *2.1.1.1 Oleuropein*

Oleuropein (OL) is a glycosylated secoiridoid that uniquely exists in plants of the Oleaceae family, presented in olive leaves at higher concentrations, and representing 1–14% of olive leaf weight, includes oleuropein in contrast with 0.005–0.12 % of olive oil weight [25, 29, 30]. OL is also known as a coumarine-like compound presented in olive trees [8]. It is an elenolic ester of hydroxytyrosol (HT), in addition to an oleosidic skeleton possessed in common to the secoiridoid glucosides of Oleaceae

[11]. In fact, HT, known as 2-(3,4-Di-hydroxyphenyl)-ethanol is the precursor of OL and the major phenolic compound in extra virgin olive oil [25, 31]. The chemical formula of one oleuropein molecule is C25H32O13 with molar mass equals to 540.518 g.mol−1 in its standard state (at 25°C [77°F], 100 kPa) (**Figure 3**) [32]. OL has been distinguished in olive flesh, leaf, seed and peel of green (unripe) olive and is an active substance of olive leaves. Its concentration declines during maturation phase happening in olive fruits because of undergoing hydrolysis yielding different products, such as HT [8, 33, 34]. It creates the bitter taste of olive that must be removed by immersion in lye, hence generating an edible olive, known as table olive [29]. OL content in olive leaves varies depending on the cultivar, production area and leaf tissue conditions (frozen, dried or fresh) [11]. There is the possibility of extracting OL molecules by some special methods explained in the following.
