**1. Introduction**

The International Organisation of Vine and Wine (OIV) recently reported that 248–294 (an average of 266) million hectoliters of wine was produced each year, globally, in between the years of 2016 to 2020 [1]. These figures highlight the scale at which wine is produced to satisfy a large global demand. It is estimated that for every 100 L of wine produced, 18–35 kg of grape pomace (the unwanted grape stems, skins and seeds) exits out as a waste product [2]. There are concerns that this large and accumulating waste mass will become unmanageable and have negative impacts towards the environment [3–6]. Other than to discard it as landfill, other practices currently employed to manage this waste are to reuse the material either as compost or livestock feed [3,6]. However, employments of these methods to break down the pomace are not without their limitations. The high phenolic content within the material leads to germination problems, and the polymeric compounds (i.e., lignins) poses issues for animal digestion [3]. The environmental concerns have led governmen<sup>t</sup> bodies to place stringent policies around managing this waste and, in some cases, has resulted in financial penalties on wine producers [7,8]. This has encouraged a need to explore novel strategies in utilizing grape pomace for higher value purposes. Development of these strategies has also been driven by consumer demands for both naturally sourced starting materials and sustainable practices, which include implementing the reusing and recycling of waste products in the production process to achieve a circular economy model [9,10].

Grape pomace contains a variety of valuable compounds, including lignins, aroma precursors, sugars, proteins, unsaturated fatty acids and phenolics [3,4]. These compounds

**Citation:** Lo, S.; Pilkington, L.I.; Barker, D.; Fedrizzi, B. Attempts to Create Products with Increased Health-Promoting Potential Starting with Pinot Noir Pomace: Investigations on the Process and Its Methods. *Foods* **2022**, *11*, 1999. https://doi.org/10.3390/ foods11141999

Academic Editors: Marco Poiana, Francesco Caponio and Antonio Piga

Received: 20 May 2022 Accepted: 3 July 2022 Published: 6 July 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/).

have properties that can be exploited to provide benefits to consumers and are attractive for various commercial applications. Phenolics (which includes polyphenols) in grape pomace, for example, comprise of a diverse set of compounds that are further classified into groups (such as phenolic acids, flavonoids and stilbenes) based on their core chemical structures. Polyphenols are well known for their biological activity and have demonstrated their ability to exert antioxidant, antiproliferative, anti-inflammatory, antimicrobial and neuroprotective effects [3,4,11,12]. It has been proposed that the recovery of valuable compounds from grape pomace could be further processed and applied for purposes such as food fortification [13], food processing [9,14], food preservation [15], improving wine quality [16], antibacterial materials [17] and cosmetic use [18]. Additionally, given their bioactive properties, it has been suggested that polyphenolic compounds could be sourced as starting materials and converted into products that directly deliver healthpromoting effects [4,19]. In the literature, there are a number of examples in which grape pomace extracts, which have higher or more concentrated phenolic contents, were found to exhibit antioxidant, antimicrobial, anti-inflammatory and antiplatelet activities [20–22], as well as promising antiproliferative or cytotoxic activities against cancer cells [23,24]. These studies were validated based on chemical, biochemical and in vitro studies and are promising indications for the health-promoting potential of the pomace. There are, however, fewer examples of in vivo studies that demonstrate the health-promoting effects of grape pomace products in animals or humans. As one example, Olivero-David et al. demonstrated that their grape by-product extract was able to the lower cholesterol levels in Wistar rats, which has implications towards hypercholesterolemia [25]. The scarcity of such studies is due to the fact that bioactive polyphenols have poor oral bioavailability, and this severely limits their effects in live models [26,27]. One major contributing factor to their low bioavailability is that these compounds are highly susceptible to metabolism by the enzymes they encounter as they pass through compartments such as the intestinal cells and the liver before reaching the systemic circulation [28,29]. These enzymatic activities convert these compounds into metabolite products that are inactive and more easily eliminated from the body. This is a large barrier that needs to be overcome. The ability to increase their bioavailability enables higher amounts of the active compounds to enter into the systemic circulation, be transported to the cells and tissues of interest and be able to exert the desired health-promoting activities. Further, if these compounds can be structurally manipulated to have increased activity (i.e., increased binding affinity to their biological targets), then this reduces the amounts of active compounds required around the active sites to exert these health effects. Therefore, the strategy for developing health-promoting products from grape pomace must thoroughly consider a process that can both effectively extract the bioactive polyphenolic compounds from the waste material and make the appropriate adjustments to these compounds that would enhance the properties needed for health promotion, including increased bioavailability and bioactivity.

The aim of the study was to develop a process whereby bioactive polyphenolics could be sourced from grape pomace, used as starting materials and modified into products with improved health-promoting properties. This work drew inspiration from previously reported studies conducted by our research group, which presented findings on the use of a simple method for extracting polyphenolics from grape pomace [30] and the structural modifications to flavonoids that led to improved bioactivity [31,32]. It was proposed that the integration of these methods could be a feasible process to achieve the study aim. Unfortunately, in following this proposed process, the expected outcome was not achieved. Despite that, the investigations of these methods did generate results that are worth presenting. This report aims to describe and discuss these methods, including the rationale and considerations underlying the decisions to use and adapt them, and the results. Following that, limitations to these methods are explored and improvements are suggested.
