**1. Introduction**

Urolithins are natural polyphenolic compounds obtained from ellagic acids and ellagitannins by the gut microbiota. Ellagic acid is a phenolic antioxidant compound present in numerous fruits, such as pomegranates, strawberries, or nuts. Ellagitannins are a class of polymeric ellagic acid derivatives also present in pomegranates (punicalagins and punicalins) and other sources, such as oak or chestnut wood (castalagin, castalin, roburin A, grandinin) or *Melaleuca quinquenervia* leaves (castalin and grandinin) [1–3].

The beneficial properties of these plants and foods seem to be in relation with these polyphenolic metabolites; however, the metabolism of polyphenols from food seems to be insufficient to achieve adequate levels of urolithins in the body. In addition, it has been proven that apparently beneficial foods such as pomegranates have had a lot of interindividual variability due to the different urolithin metabotypes present in the population [4]. In fact, only 1 in 3 people have the right microbiota to perform this metabolism with maximum efficiency [5].

Therefore, it is very important to evaluate the activity of isolated urolithins as potential therapeutic agents. In addition, the use if urolithin A in humans and the safety profile of this compound have been widely evaluated, with no adverse effects on health observed [6].

Although urolithins are a group of metabolites, urolithin A (UA), also known as 3,8-dihydroxyurolithin, is one of the most representative compounds. There are numerous studies that demonstrate an important role of this compound in metabolic syndrome, improving cardiovascular function, decreasing the formation of triglycerides, inhibiting enzymes such as lipase or glucosidase, or relieving insulin resistance [7–9]. It has also been observed that UA may have an important role in the prevention of certain cancers, such as colorectal or prostate cancers [10,11]. UA also has an important role at the mitochondrial level, being able to activate mitophagy and prolonging lifespan in *Caenorhabditis elegans* worms, as well as beneficial mitochondrial effects in the skeletal muscle [12,13].

The set of all these beneficial properties for health may be due to the antioxidant capacity of polyphenols. However, there are few studies that link the antioxidant properties of this metabolite with a potential therapeutic activity in neurodegenerative diseases, where the redox status is essential. Therefore, the objective of this study was to evaluate whether urolithin A has antioxidant and neuroprotective effects using Neuro-2a cells and other in vitro models involving the use of central nervous system (CNS) enzymes or free radicals.
