Flavonoids and polyphenols are heterocyclic molecules that have been associated with beneficial effects on human health, such as reducing the risk of various diseases like cancer, diabetes, and cardiovascular and brain diseases. Protocatechuic acid (PCA) is a type of widely distributed naturally occurring phenolic acid. PCA has structural similarity with gallic acid, caffeic acid, vanillic acid, and syringic acid which are well-known antioxidant compounds. More than 500 plants contain PCA as active constituents imparting various pharmacological activity and these effects are due to their antioxidant activities, along with other possible mechanisms, such as anti-inflammatory properties and interaction with several enzymes. Over the past two decades, there have been an increasing number of publications on polyphenols and flavonoids, which demonstrate the importance of understanding the chemistry behind the antioxidant activities of both natural and synthesized compounds, considering the benefits from their dietary ingestion as well as pharmacological use. This work aims to review the pharmacological effects of PCA molecules in humans and the structural aspects that contribute to these effects. 1. Introduction Polyphenols are the most voluminous antioxidants in human diets. These polyphenols are to be categorized in different classes as phenolic acids, flavonoids, lignans, and stilbenes. Phenolic acids are naturally occurring compounds found in plant kingdom with unique structural similarities, presence of carboxylic group as in caffeic acid, gallic acid, p-coumaric acid, vanillic acid, ferulic acid, and protocatechuic acid (PCA) [1] (Figure 1). Protocatechuic acid (PCA) is widely distributed and present in most edible plants used in folk medicine [2]. It is also a very common compound present in human diet, present in bran and grain brown rice (Oryza sativa L.) [3] and onion (Allium cepa L.) [4], especially in the scales. Protocatechuic acid is detected in many fruits, such as plums (Prunus domestica L.) [5]; gooseberries (Ribes uva-crispa L.) [6]; grapes (Vitis vinifera) [6]; and nuts, such as almonds ordinary (Prunus amygdalus) [7]. It is present in products of plant origin, such as olive oil or white wine [8, 9]. Protocatechuic acid is also found in many plants and spices, such as star anise (Illicium verum), melissa (Melissa officinalis L.), a medical rosemary (Rosmarinus officinalis L.), and cynamonowa (Cinnamomum aromaticum) [4]. This compound is one of the biologically active components of some medicinal plants, including those used in natural
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