## 1 Introduction  
The large amount of phenolic compounds present in olive leaves has attracted the interest of researchers and many studies have reported that olive leaves provide beneficial effects such as antioxidant capacity, antihypertensive, cholesterol lowering, cardioprotective, anti-inflammatory and as a coadjuvant in the treatment of obesity [1, 2, 3, 4, 5, 6, 7]. The extraction process is the main step in the recovery and isolation of bioactive compounds from plant samples [8]. Conventional extraction by maceration has several disadvantages such as low phenolic recovery, longer extraction times, toxic solvents and high energy consumption [9]. Therefore, green extraction techniques such as microwave-assisted extraction (MAE) have been developed to resolve the disadvantages of conventional extraction by reducing the extraction time and solvent consumption. This method is also respectful of the environment and it is economical [10]. Microwaves are electromagnetic fields in the frequency between 0.3 and 300 GHz. Microwaves can penetrate some materials and interact with the polar components to generate heat [11]. Heat improves the diffusivity of phenolic compounds from the matrix to the solvent [12]. Several parameters can affect the extraction efficiency of MAE, including microwave power, extraction time, solvent type and composition, liquid to solid ratio, sample particle size, soaking time, and number of extraction cycles [13]. With regard to the solvent, it is important that it provides high extracting power and strong interplay with the matrix and the bioactive compounds. Thus, ethanol and water are suitable in MAE because they can absorb microwave energy due to their high dielectric constant and dielectric loss, and they are also safe to use in the food industry [14; 15]. Other important parameters in MAE are the time of extraction and the temperature. Short extraction times are used in MAE to avoid the degradation of the chemically active structures of phenolic compounds. On the other hand, high temperatures cause a decrease in viscosity and surface tension, which results in better solvent penetration. However, high temperatures can also break down the molecular structure of bioactive compounds, which results in a decrease in the extraction yield [16]. For these reasons, it is important to determine the optimum value of these MAE parameters in order to improve the extraction recovery of bioactive compounds. Several studies have reported that secoiridoids present in extra virgin oil and olive leaves have the capacity to activate the AMP-activated protein kinase (AMPK) [17; 18]. This protein is the major regulator of energy metabolism at both the cell and the whole body level [19; 20]. Acute activation of AMPK in adipose tissue suppresses lipolysis, whereas chronic pharmacological stimulation of this enzyme remodels adipocyte metabolism to promote energy dissipation and prevent re-esterification of fatty acids (FAs). These specific tissue effects indicate that this enzyme is suitable in the treatment of obesity and its related metabolic disorders [21]. In addition, it has been reported that olive leaf extract decreases intracellular lipid accumulation through AMPK dependent mechanisms in hypertrophic adipocytes [22]. It has been suggested that this effect is due to the presence of several fractions in olive leaf extract that contain specific compounds belonging to the secoiridoids, phenylethanol, phenylpropanoids and flavonoids subclasses [22]. High recovery of these bioactive compounds from olive leaves can be achieved by optimizing the extraction conditions. In this study, an experimental Box-Behnken response surface design was used to optimize the MAE parameters of temperature, solvent composition and extraction time to obtain the highest total compounds content and compounds with the capacity to activate AMPK from olive leaves.