**1. Introduction**

Nowadays, there is an increasing attention on the food we eat. There is a worldwide great demand of minimally processed food or food ingredients with functional properties because of a new awareness of how a healthy and sustainable living is important. Bioactive food compounds, also known as phytochemicals, have the capacity to regulate most of the metabolic processes resulting in health benefits. So far, about 10,000 phytochemicals have been identified, but a large percentage remains still unknown. The identified phytochemicals include tannins, flavones, triterpenoids, steroids, saponins, and alkaloids. Numerous

**Citation:** Matrella, M.L.; Valletti, A.; Marra, F.; Mallamaci, C.; Cocco, T.; Muscolo, A. Phytochemicals from Red Onion, Grown with Eco-Sustainable Fertilizers, Protect Mammalian Cells from Oxidative Stress, Increasing Their Viability. *Molecules* **2022**, *27*, 6365. https:// doi.org/10.3390/molecules27196365

Academic Editor: Nour Eddine Es-Safi

Received: 11 August 2022 Accepted: 21 September 2022 Published: 27 September 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

studies have associated the protective and beneficial roles of phytochemicals with their antioxidant activity, since the overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is the cause of cellular aging [1], and of many chronic diseases [2]. Antioxidant phytochemicals exist widely in fruits, vegetables, cereal grains, edible macrofungi, microalgae, and medicinal plants. Among the vegetables rich in bioactive compounds, *Allium cepa* L. (the common onion) is one of the oldest plants cultivated around the world and consumed as a vegetable and spice. It is greatly appreciated as a medicinal plant in traditional medicine for its high content of phytochemicals, including polyphenols, flavonoids, and sulphur-based compounds. These secondary metabolites, widely contained in onions, have a different mode of action and biosynthetic pathways but are all able to promote beneficial health effects. A regular onion bulb intake is reported to have profound radical scavenging activity and several beneficial effects on health [3], such as preventing cardiovascular diseases [4], diabetes [5], cancers [6], and neurodegeneration [7]. Therefore, foods in our diet that can aid in the prevention of these diseases are of major interest to both the scientific and public communities.

Epidemiological data evidenced that a high intake of onions was positively correlated with a low risk of carcinoma [8,9]. Hertog and Katan [10] showed that a high consumption of quercetin-rich onion was associated with a 50% cancer risk reduction of the digestive and respiratory tracts. Organosulphur compounds such as diallyl disulfide (DDS), Sallylcysteine (SAC), and S-methylcysteine (SMC) have been demonstrated to inhibit colon and renal carcinogenesis [11,12]. Phytochemicals act through two different mechanisms: cancer cell apoptosis induction [13] and gene transcription inhibition [14].

The quantity and quality of bioactive compounds contained in the onion bulb can vary according to the variety and cultivation practices. Among the varieties, it was welldemonstrated that *A. cepa L. var. tropeana* (red onion) contains more phytochemicals than white onion [15]. With respect to the cultivation conditions, numerous researchers have evidenced that onion is a sulphur-loving crop and that sulphur increased the bulb yield quality and flavors. Other works indicated an increase in onion quality when organic fertilizers were used [16]. Muscolo et al. [17] showed that the use of sulphur-organic-based fertilizers increased, in red onion, the production of bioactive organosulphur compounds and antioxidants with respect to the type and concentration of sulphur-organic-based fertilizer used.

Based on the above findings, the main aims of the current research were to: (1) determine the chemical characteristics, phytochemical amount, and profile of red onion bulbs differently fertilized and (2) evaluate their biological activity in normal and oxidative stress conditions. The lyophilized onion bulbs were tested in two cellular models, i.e., the H9c2 rat cardiomyoblast cell line and primary human control, and *parkin*-mutant fibroblasts in terms of viability and oxygen radical homeostasis. H9c2 cells are a valid alternative for primary cardiomyocytes where oxidative stress is an important pathophysiological pathway, affecting multiple aspects of cardiac functionality, including signal transduction, cell cycle arrest, apoptosis, and necrosis [18,19]. In Parkinson's disease (PD), oxidative stress plays a significant role in the cascade, consequently leading to the degeneration of dopaminergic neurons. Moreover, other aspects of the degenerative process, such as mitochondrial malfunction, excitotoxicity, nitric oxide toxicity, and inflammation, are all linked to oxidative stress [20]. Our goal was to link the protective benefits of red onion to the phytochemical content and specific class of compounds in order to emphasize the medicinal worth of these onions, which may be used in a health prevention program.
