**4. Conclusions**

*P*. *dulcis* or the so-called almond is a rich source of antioxidant phenolic compounds that are retained, after almond cold-pressed oil extraction, in a skin-enriched by-product which, thus, represent an attractive starting material for their extraction. As natural antioxidants, these phenolic compounds' almond attracted much attention as alternatives to synthetic antioxidants in foods, pharmaceutical, and cosmetic preparations. Here, using a multivariate Box–Behnken design coupled with surface response methodology, we proposed an optimized and validated USAE of these phenolic compounds from cold-pressed AOR. Optimal conditions for USAE were: aqEtOH 53.0% (*v*/*v*) as

green solvent, US frequency 27.0 kHz and extraction duration 29.4 min. Following its optimization, the present USAE method was validated according to international standards to ensure its precision and accuracy in the quantitation of total phenolic content. The e fficiency of the present USAE has allowed substantial gains in terms of extraction e fficiency compared to conventional heat reflux extraction—in particular by a strong reduction in extraction time, which is of particular interest in the context of green chemistry in terms of reduction of energy consumption, together with the use of a green extraction solvent. The application of this method already makes it possible to sugges<sup>t</sup> a higher impact of the genetic background than of the environment on three genotypes cultivated on three experimental sites. This method therefore opens the door to more complete studies on this subject. Finally, both in vitro cell free and cellular antioxidant assays revealed the grea<sup>t</sup> potential of valorization of these extracts as a source of natural antioxidants. To summarize, the present extraction method allows a quick, green, simple, and e fficient validated USAE for the possible valorization of antioxidant phenolic compounds from Moroccan almond cold-pressed oil residues, making it possible to generate extracts with attractive antioxidant activities for future nutraceutical and/or cosmetic applications.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3417/10/9/3313/s1, Figure S1: Biplot representation of the linear relation between predicted vs. measured TPC in the 18 Box–Behnken design sample extracts; Figure S2: Loading scores of the first and second axis of the principal component analysis; Table S1: Actual values for PCC (Pearson Correlation Coe fficient) showing the relation between the di fferent phytochemicals and antioxidant assays.

**Author Contributions:** Conceptualization, D.T., A.E., M.A. (Mohamed Addi), and C.H.; Methodology, D.T., A.E., M.A. (Malika Abid), S.D., R.K.; L.G., A.K., M.A. (Mohamed Addi), and C.H.; Software, S.D.; Validation, M.A. (Mohamed Addi), C.H., D.T.; Formal analysis, M.A. (Mohamed Addi), C.H., S.D., and D.T.; Investigation, S.D., D.T., and R.K.; Resources, M.A. (Mohamed Addi) and C.H.; Data curation, M.A. (Mohamed Addi) and C.H.; Writing—original draft preparation, C.H.; Writing—review and editing, M.A. (Mohamed Addi), D.T., A.K., and C.H.; Visualization, C.H. and S.D.; Supervision, M.A. (Mohamed Addi) and C.H.; Project administration, M.A. (Mohamed Addi) and C.H.; Funding acquisition, M.A. (Mohamed Addi) and C.H. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by Cosmetosciences, a global training and research program dedicated to the cosmetic industry. Located in the heart of the Cosmetic Valley, this program led by University of Orléans is funded by the <sup>R</sup>égion Centre-Val de Loire.

**Acknowledgments:** D.T. gratefully acknowledges the support of French governmen<sup>t</sup> via the French Embassy in Thailand in the form of Junior Research Fellowship Program 2018. S.D. and L.G. acknowledge the research fellowship of the Loire Valley Region. K.R. acknowledges the research fellowship from the Ministry of Science, Research and Technology of Iran.

**Conflicts of Interest:** The authors declare no conflict of interest.
