*Article* **Phytochemicals from Red Onion, Grown with Eco-Sustainable Fertilizers, Protect Mammalian Cells from Oxidative Stress, Increasing Their Viability**

**Maria Laura Matrella 1,†, Alessio Valletti 1,†, Federica Marra 2,†, Carmelo Mallamaci 2,†, Tiziana Cocco <sup>1</sup> and Adele Muscolo 2,\***


**Abstract:** Red onion, a species of great economic importance rich in phytochemicals (bioactive compounds) known for its medicinal properties, was fertilized with sulphur-bentonite enriched with orange residue or olive pomace, with the aim of producing onion enriched in health beneficial compounds. There is a worldwide great demand of minimally processed food or food ingredients with functional properties because of a new awareness of how important healthy functional nutrition is in life. Phytochemicals have the capacity to regulate most of the metabolic processes resulting in health benefits. Red onion bioactive compound quantity and quality can vary according to cultivation practices. The main aims of the current research were to determine the chemical characteristics of the crude extracts from red onion bulbs differently fertilized and to evaluate their biological activity in normal and oxidative stress conditions. The lyophilized onion bulbs have been tested in vitro on two cellular models, i.e., the H9c2 rat cardiomyoblast cell line and primary human dermal fibroblasts, in terms of viability and oxygen radical homeostasis. The results evidenced different phytochemical compositions and antioxidant activities of the extracts obtained from red onions differently fertilized. Sulphur-bentonite fertilizers containing orange waste and olive pomace positively affected the red onion quality with respect to the red onion control, evidencing that sulphur-bentonite-organic fertilization was able to stimulate plant a secondary metabolism inducing the production of phytochemicals with healthy functions. A positive effect of the extracts from red onions treated with fertilizers—in particular, with those containing orange waste, such as the reduction of oxidative stress and induction of cell viability of H9c2 and human fibroblasts—was observed, showing a concentration- and time-dependent profile. The results evidenced that the positive effects were related to the phenols and, in particular, to chlorogenic and p-coumaric acids and to the flavonol kaempferol, which were more present in red onion treated with low orange residue than in the other treated ones.

**Keywords:** red onion; phytochemicals; polyphenols; oxidative stress; H9c2 rat cardiomyoblast; primary human fibroblasts
