**Enhanced Recovery of Antioxidant Compounds from Hazelnut (***Corylus avellana* **L.) Involucre Based on Extraction Optimization: Phytochemical Profile and Biological Activities**

**Marius Emil Rusu 1,**†**, Ionel Fizes, an 2,**†**, Anca Pop 2,\*, Ana-Maria Gheldiu 3,\*, Andrei Mocan 3, Gianina Cris, an 3, Laurian Vlase 1, Felicia Loghin 2, Daniela-Saveta Popa <sup>2</sup> and Ioan Tomuta <sup>1</sup>**


Received: 13 August 2019; Accepted: 5 October 2019; Published: 8 October 2019

**Abstract:** Tree nut by-products could contain a wide range of phytochemicals, natural antioxidants, which might be used as a natural source for dietary supplements. The aim of the present study was to evaluate the phenolic and sterolic composition, as well as the antioxidant and other biological activities, of hazelnut involucre (HI) extracts. Experimental designs were developed in order to select the optimum extraction conditions (solvent, temperature, time) using turbo-extraction by Ultra-Turrax for obtaining extracts rich in bioactive compounds. Qualitative and quantitative analyses were performed by LC-MS and LC-MS/MS and they revealed important amounts of individual polyphenols and phytosterols, molecules with antioxidant potential. The richest polyphenolic HI extract with the highest antioxidant activity by TEAC assay was further evaluated by other in vitro antioxidant tests (DPPH, FRAP) and enzyme inhibitory assays. Additionally, the cytotoxic and antioxidant effects of this extract on two cancerous cell lines and on normal cells were tested. This is the first study to analyze the composition of both hydrophilic and lipophilic bioactive compounds in HI extracts. Our findings reveal that this plant by-product presents strong biological activities, justifying further research, and it could be considered an inexpensive source of natural antioxidants for food, pharmaceutical, or cosmetic industry.

**Keywords:** hazelnut involucre; antioxidants; polyphenols; phytosterols; biological activity; experimental design; LC-MS; turbo-extraction; Ultra-Turrax; enzymatic inhibition
