**1. Introduction**

The study of plant-derived compounds received increased attention among researchers worldwide in the attempt to discover new bioactive molecules with marked therapeutic actions and minimal adverse effects. A healthy diet and regular exercise protect the human body from cardiovascular problems, diabetes, and cancer [1]. The definition of a healthy diet is permanently evolving and changing to comprise all the knowledge with respect to different foods, nutrients or food components in health and disease. Thus, a healthy food approach refers to diets rich in plant-based foods (fresh fruits, vegetables, legumes, seeds, whole grains, nuts) and low in animal-based products (e.g., fatty and processed meats) [2]. Therefore, WHO recommends consuming 400 g (5 portions) of fruit and vegetables to our

**Citation:** Chedea, V.S.; Macovei, S, .O.; Bocsan, I.C.; M ˘agureanu, D.C.; Levai, A.M.; Buzoianu, A.D.; Pop, R.M. Grape Pomace Polyphenols as a Source of Compounds for Management of Oxidative Stress and Inflammation—A Possible Alternative for Non-Steroidal Anti-Inflammatory Drugs?. *Molecules* **2022**, *27*, 6826. https://doi.org/ 10.3390/molecules27206826

Academic Editor: Nour Eddine Es-Safi

Received: 15 September 2022 Accepted: 9 October 2022 Published: 12 October 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/).

diet [3] because they possess significant levels of phytochemicals like flavonoids, stilbenes, lignans, and phenolic acids found in different concentrations [1,4,5].

Grapes, with a global production of around 78 million tons in 2020 [6], and with around 75% of total production going into the wine industry, are such an example. One of the main reasons for grapes research is the quantity of waste resulting from the juice and winemaking process [7–9]. An important by-product of the winemaking industry is grape pomace (GP), and due to the important consumption of wine (27 million tons in 2019) [6], there are also important quantities of GP generation (8.49 million tons) [10]. Disposal of this by-product causes an ecological problem because of pollution and other hazardous issues that come with producing large quantities in a short time and little space for deposit [11]. To overcome these, different solutions were proposed for by-products valorization, including the recovery of containing bioactive compounds like phenolic compounds [12–14]. Polyphenols have beneficial effects on various diseases, especially because of their anti-inflammatory and antioxidant effects via different mechanisms [15–17]. Accordingly, it was observed that GP, because of its various and rich quantity of phenolics has potential antioxidant, anti-inflammatory, anti-microbial, anti-cancer effects and also beneficial cardiovascular and hepatic effects [18–21]. Knowing that oxidative stress and inflammation processes are common to many diseases, this review will focus especially on these pathophysiological processes since their management is a key step in the attempt to prevent or reduce disease progression. Thus, their modulation by polyphenols from GP as reported in both *in vitro* and *in vivo* studies will be addressed. Also, another important aim of this review is to compare the anti-inflammatory effects of GP polyphenols with the one of non-steroidal anti-inflammatory drugs (NSAIDs). Non-steroidal anti-inflammatory drugs are used for medical purposes since ancient times, being one of the most prescribed drug classes in the world. They possess anti-inflammatory, antipyretic, and analgesic effects and therefore are prescribed for many diseases, especially chronic diseases like rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and chronic pain [22–24]. Unfortunately, the therapeutic effects can be associated with pulmonary, renal, gastrointestinal, cardiovascular, and hepatic adverse reactions that might lead to severe complications [25–28]. Thus, there is an urgent need in identifying novel antioxidant and anti-inflammatory agents, therapeutically potent and with minimal side effects that could be used instead of classical drugs or as add-on therapy, and GP could be a source of such kind of compounds.
