Resveratrol-based biorefinery models for favoring its inclusion along the market value-added chains: A critical review

Science of the Total Environment 908 (2024) 168199 Available online 31 October 2023 0048-9697/© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/). Review Resveratrol-based biorefinery models for favoring its inclusion along the market value-added chains: A critical review Ana Arias a , * , Carlos E. Costa b , c , Maria Teresa Moreira a , Gumersindo Feijoo a , Lucília Domingues b , c a CRETUS, Department of Chemical Engineering, School of Engineering, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain b CEB - Center of Biological Engineering, University of Minho, 4710-057 Braga, Portugal c LABBELS - Associate Laboratory, Braga, Guimar˜ aes, Portugal HIGHLIGHTS GRAPHICAL ABSTRACT •Resveratrol produced by agro-industrial waste valorization leads to more efficient and sustainable waste management. •Green extraction and biosynthesis technologies for resveratrol are more effective and beneficial than conventional ones. •Further analysis and optimization is needed for the effective and feasible scale-up of emerging technologies. •Integration of resveratrol production on biorefinery schemes could enhance its penetration on the market value chains. •Sustainability assessments are crucial to demonstrate the benefits of resveratrol industrialization and market penetration. ARTICLE INFO Editor: Frederic Coulon Keywords: Resveratrol Renewable resources Extraction techniques Biorefinery Circular economy Market value chain ABSTRACT Resveratrol, a natural organic polyhydroxyphenolic compound, has gained significant attention in the last years given its potential health benefits, including antioxidant, anti-cancer, and anti-inflammatory properties. It can be directly extracted from plants, vegetables, and related products and waste resources, but also chemically/ enzymatically/microbially synthesized. However, certain process strategies have some limitations, such as high costs, reduced yield or high energy demand, thus implying significant environmental loads. In this context, the search for more sustainable and circular process schemes is key to the integration of resveratrol into the market value chain of the food, cosmetic and pharmaceutical sectors. The extraction of resveratrol has traditionally been based on conventional methods such as solvent extraction, but advanced green extraction techniques offer more efficient and environmentally friendly alternatives. This review analyses both conventional and green alternative extraction technologies, as well as its bioproduction through microbial fermentation, in terms of production capacity, yield, purity and sustainability. It also presents alternative biorefinery models based on resveratrol bioproduction using by-products and waste streams as resources, specifically considering wine residues, peanut shells and wood bark as input resources, and also following a circular approach. This critical review provides * Corresponding author. E-mail address: [email protected] (A. Arias). Contents lists available at ScienceDirect Science of the Total Environment journal homepage: www.elsevier.com/locate/scitotenv https://doi.org/10.1016/j.scitotenv.2023.168199 Received 10 September 2023; Received in revised form 25 October 2023; Accepted 27 October 2023 Science of the Total Environment 908 (2024) 168199 2 some insight into the opportunities that resveratrol offers for promoting sustainable development and circularity in the related market value chains, and thus provides some criteria for decision making for biorefinery models in which resveratrol is one of the targeted high value-added products. It also identifies the future challenges to promote the inclusion of resveratrol in value chains, with the scale-up of green technologies and its demonstrated economic feasibility being the most prominent. 1. Introduction The first resveratrol isolation dates from 1939 using white hellebore as bioresource (Veratrum grandiflorum O. Loes) (Takaoka, 1939), which is classified as a species of poisonous perennial herbs of the Melanthiaceae spp.. Later, it was isolated from the roots of Polygonum cuspidatum syn. Fallopia japonica, also known as Japanese knotweed, a wellrecognized plant given its high content of polyphenolic trans-resveratrol, being the highest bioavailable form of resveratrol that can be extracted and isolated from bio-based resources (Kaur et al., 2022; Suvarna et al., 2018). Resveratrol can be found on various plants, fruits, and herbaceous species, but its functions can vary depending on the bioresource of extraction (Donnez et al., 2009). For example, grapevine, one of the most recognized raw materials for the extraction of resveratrol, provides a product with antifungal properties, while in berries and plant leaves, its main function is to respond to stress situations, acting as a phytoalexin, i.e. antimicrobials with protective functions belonging to the iso/ flavonoid family of phenolic-based compounds (Tuladhar et al., 2021). Furthermore, resveratrol can be found in more wood-nature sources, in which its main behavior is to act as a phytoanticipin, a precursor of an antimicrobial compound against pathogens (Tiku, 2020). Given the benefits that resveratrol can provide, resveratrol bioavailability has been enhanced by encapsulation in nanoparticles or liposomes (Jayan et al., 2019; Davidov-Pardo and McClements, 2014), co-administration with adsorption enhancers as piperin, a compound that could be found on black pepper (Vesely et al., 2021; Johnson et al., 2011) or by the development of controlled and sustained release formulations (Chimento et al., 2019; Devi et al., 2019). Interest in resveratrol has been increasing year after year, given its potential and interesting properties as an antioxidant, cardioprotective, cancer preventive agent, neuroprotective, anti-inflammatory, among others (Abo-Kadoum et al., 2022; Gugleva et al., 2020; Majeed et al., 2023; Zhang et al., 2022). However, one of its main drawbacks is that most commercial forms of resveratrol are produced chemically, as it is more economically viable and meets market demands (Lorena et al., 2018). Some of the commercial products are extracted from plants, but the procedures are not efficient, and the extraction yield is low. With this in mind, the introduction of biotechnological production processes and/ or environmentally-friendly processes for extraction is key to increase their quality, natural nature and commercialization. In this context, this critical review is developed to present the bioactive potentials of resveratrol, together with the main bio-based and waste resources that can be used for its extraction, followed by the description of the valorization technologies available for its extraction, as well as its bioproduction, with a special focus on the usage of renewable substrates. In addition, in order to provide a broader view and potential of resveratrol in the market value chain, alternative biorefinery scenarios are described. It is hoped that the information provided by this critical review can help researchers, policy makers, stakeholders and manufacturers to advance the recovery and biotechnological production of resveratrol from waste-related streams, seeking to provide more sustainable production pathways based on the comprehensive use of available resources. 2. Resveratrol: properties, uses and market trends Resveratrol belongs to the polyphenol stilbenes group, concretely being a 3,5,4-trihydroxy-trans-stilbene, with an ethylene bridge in which two phenol groups are bonded. It has an average molecular weight of 228 g/mol, with 14 carbon skeletons (Thirumalaisamy et al., 2022). It has two geometric isomers, cis-resveratrol and trans-resveratrol, being the trans isomer the one associated with its biological functions and properties, and also the dominant geometrical structure (Salehi et al., 2018a, 2018b). One of the most promising features of resveratrol is its antioxidant properties, which implies potential health benefits (Fraga et al., 2019). The antioxidant effects of resveratrol could be provided by various mechanisms, including its actuation as free radical scavenger (resveratrol donate electrons to superoxide anions, hydroxyl and peroxynitrite radicals, thus stabilizing them and avoiding cell damage), neutralization of reactive oxygen species (ROS), reaction with nitrogen free compounds (RNS) and it could also activate various antioxidant enzymes, as the cases of superoxide dismutase and catalase, which may also help to combat cellular oxidative stress and thus maintain cellular redox balance (Bononi et al., 2022a, 2022b; Heo et al., 2018). The latter case is known as “indirect antioxidant activity” as it could act as a regulator for these enzymes and thus enhancing the body defense system (Truong et al., 2018; Xia et al., 2017). Besides, resveratrol could also chelate metal ions, including iron and copper, which are known as important enhancers of high reactive free radicals by developing Fenton and Haber-Weiss reactions (Aaseth et al., 2021; Salehi et al., 2018a, 2018b). Another antioxidant effect of resveratrol is through the inhibition of lipid peroxidation, which is a chain reaction that also promotes cell damage, and mitochondrial protection in cellular respiration (a source of ROS) (Pinyaev et al., 2019; Gimeno-Mallench et al., 2019). Apart from the antioxidant properties, resveratrol also stands out for its potential to provide antimicrobial functions (Abedini et al., 2021; Karamese and Dicle, 2022). It has been identified that it has activity against multidrug-resistant Gram-negative bacteria with a minimal inhibitory concentration between 32 μ g/mL and 128 μ g/mL, following an inhibition action analogous to that of efflux pump inhibitors (Inchingolo et al., 2022; Ma et al., 2018). Given this, resveratrol has the ability to rejuvenate the functionality of antibiotics against bacterial pathogens (Sharma et al., 2019). On the other hand, resveratrol could also induce the expression of antimicrobial peptides (AMPs), which are crucial proteins in the immune system for defense against pathogens and microbial infections (Lan et al., 2017). Besides, it positively modulates gut microbiota, considered as essential for the preservation of a balanced immune system (Wang et al., 2022; Inchingolo et al., 2022) and also it has demonstrated its good combination with other antimicrobial agents, thus enhancing microbial resistance (Liu et al., 2020; Skroza et al., 2019; Vestergaard and Ingmer, 2019). It has been demonstrated that resveratrol has the capacity to inhibit the replication and expression of rhinovirus, the cause of common respiratory diseases, as well as other illness related with high-fat diets, as hepatic steatosis or hyperglycemia, given the efficacy of resveratrol to reduce the amount of glucose, total cholesterol and triglycerides, among others (Su et al., 2022; Mastromarino et al., 2015). But, it should be taking into account that, even with its benefits, the amount of resveratrol intake could be critic to human and animal organisms Jung et al. (2009). There are some derivatives of resveratrol with slightly different molecular and functional properties, and mechanisms of action (Thirumalaisamy et al., 2022). Resveratrol can be found in a hydroxylated form (as dihydroxy stilbene) containing higher stilbene proportion and A. Arias et al. Science of the Total Environment 908 (2024) 168199 3 lower amount of hydroxyl groups, which leads to increased water solubility and pharmacological functionality but, at the same time, reduced bio-availability within oral intake (Arbo et al., 2020). It can also be found in a methoxylated structure (as pterostilbene or trimethoxy stilbene), commonly available on berries and grapes, which has enhanced oral absorption and stability, given the addition of a methoxy group on the resveratrol structure (Nagarajan et al., 2022). On the other hand, to enhance natural resveratrol stability and water solubility, as well as bioavailability and prevention of enzymatic oxidation, the development of a glycosylation reaction has been demonstrated to be effective. It is based on the addition of glycosidic compounds (carbohydrates, such as sugars), commonly glucose, by the formation of an ether bond with the hydroxyl group of the resveratrol compound (Cole and Kramer, 2016; Lin et al., 2021). Another way to increase the bioavailability and water solubility of resveratrol for human intake is through its micro and nanoencapsulation in casein microparticles, as reported by Gani et al. (2022). For this encapsulation, resveratrol is dissolved with casein, phosphate buffer and 95 % ethanol, homogenized and ultrasonicated in periods of 5 min to avoid casein denaturation, ending with a lyophilization of the nanoparticles, which are then ready to be included in the formulation of food, pharmaceutical or cosmetic products (Arora and Jaglan, 2018; Gani et al., 2022). Other less common derivative forms are the aminated/amidated/iminated forms, based on reaction with an amine group, with enhanced antioxidant and neuroprotective properties, and the prenylated derivatives, obtained by the substitution of the hydroxy groups of the resveratrol molecule (Puksasook et al., 2017; Toume et al., 2015). Regarding resveratrol use on the market value-chain, it is mainly applied for the production of nutraceuticals, cosmetics, pharmaceuticals and for drug formulation. The rationale behind its prominent use in the aforementioned applications is based on its bioactive properties, which are beneficial for preventing cancer, liver diseases, arthritis, oxidative stress, age-related illnesses, and skin-related problems, among others (Sharifi-Rad et al., 2022). Besides, it could also be used to enhance the quality and productivity on the agricultural sector, and thus increasing the food quality, an important value chain for the bioeconomy, as it could degrade some bacteria found on the soil, on the rhizosphere, thus reducing the detrimental effects of the chemicals over the soil properties and nutrients balance (Kurt et al., 2018). Another important characteristic of resveratrol is that its properties do not alter with increasing storage time of the raw material used for its extraction. This has been the main conclusion reached when analyzing how the concentration of resveratrol varies in vine-related residues (such as shoots) or grapes stored after one, three, and six months, observing that not only its potential is maintained but increases (Cebri´ an et al., 2017). The rationale behind this fact could be explained given the influence of the environmental issues over the resveratrol content, mainly due to its polygenic trait (Guo et al., 2022). This fact also implies that even the same type of feedstock (e.g., vines or peanuts) could have a different content of resveratrol depending on the cultivated region or on the genotypes. For example, in the case of vines, the V. labrusca genotype has a much lower content in comparison to that of V. vinifera, and on peanuts, the variation in resveratrol composition could vary in the range of 125–1626 μ g/kg of peanut, which is, indeed, a significant variance (Cr˘ aciun and Gutt, 2022). In order to provide the main applications of resveratrol, the following Table 1 is included: On the other hand, according to the available reports on resveratrol market insights, it is expected to achieve an annual growth between 6.2 % and 8.4 % until 2031 (Future Market Insights, 2023a; Priya, 2021). The last data about the market size on resveratrol dates to 2022, with an amount of $118.60 million, with a projection to reach $131.0 by 2030 (Future Market Insights, 2023b; Priya, 2021). Another important fact is that there will be a significant difference between production trends between synthetic and natural resveratrol, being the latter the one that is going to increase and penetrate better on the market, and also the one with the highest growth. With respect to the applications of resveratrol, the huge market value is going to be appreciated for nutraceuticals and pharmaceuticals production, while its use on cosmetics will be lower. Considering the global scope of resveratrol, is North America the region with the higher production market, followed by Europe (Priya, 2021). 3. Sources for resveratrol extraction Various plants, including vegetables, fruits and nuts, are good examples of food products containing resveratrol in their composition. Resveratrol can be found in more than 70 plant species, highlighting its higher composition in grapes (92–1759 mg/g fresh weight), peanuts (around 0.08 μ g/g), berries (0.007–5.88 μ g/g), apples (400 mg/g), pistachio (0.09–1.67 μ g/g) and cocoa (around 1.85 μ g/g) (Bolling et al., 2010; Weiskirchen and Weiskirchen, 2016). It is important to mention Table 1 Resveratrol applications and descriptions. Application Description Reference Antioxidant Reduces oxidative stress Bononi et al., 2022a, 2022b; Zhang et al., 2021a, 2021b, 2021c Anti-inflammatory Resveratrol reduces inflammation by modulating enzymes in order to produce mediators Chowdhury et al., 2022; Udenigwe et al., 2008 Cardiovascular health The antioxidant properties also provide increase on cardiovascular health given the decrease of the oxidation of lowdensity lipoprotein-cholesterol Bhullar and Udenigwe, 2016; Das and Das, 2010 Neuroprotective functions It has demonstrated neuroprotective functions to Aβrelated toxicity Bastianetto et al., 2015 Anti-aging effects Given the induction of sirtuin expression, as sirtuins are directly related with cellular response to oxidative stress. Zhang et al., 2021a, 2021b, 2021c; Kaeberlein et al., 2005 Anti-cancer effect Could promote the inhibit of cancer cell-growth and proliferation by modulating the transduction mechanisms. Ren et al., 2021; Zhang et al., 2021a, 2021b, 2021c Metabolic functions Affect over insulin sensitivity and glucose regulation Qiu et al., 2019; Liu et al., 2014 Increase skin health By enhancing collagen synthesis and protecting against UV Jang et al., 2015; Polonini et al., 2013; Zhang et al., 2012 Increase bone health Resveratrol could promote osteoblast-mediated bone formation. Li et al., 2021; Wong et al., 2020 Anti-viral It has shown antiviral effects over some viruses related with respiratory infections Van Brummelen and Van Brummelen, 2022; Filardo et al., 2020; Cognitive function Reduction on oxidative stress of brain cells enhances the protection of neurodegenerative processes Tosatti et al., 2022; Zaw et al., 2021 Immune support It could modulate the immune response of the body by the regulatory cell suppressive functions Chen and Musa, 2021; Malaguarnera, 2019 Hormone regulation Resveratrol could balance the hormone levels, mostly with estrogen. Qasem, 2020; Gehm et al., 1997 Anti-depressant The anti-inflammatory and neuroprotective effects of resveratrol promote a positive impact on mental well-being. Chen et al., 2021; Zhu et al., 2019 Anti-hypertensive It could lower blood pressure caused by hypertension by the production of an endogenous vasodilate, as nitric oxide Theodotou et al., 2017; Movahed et al., 2016 A. Arias et al. Science of the Total Environment 908 (2024) 168199 4 that the amount of resveratrol available in these biological sources could vary depending on several factors. Factors that could significantly alter the bioavailability of resveratrol are the growing conditions of the plants and vegetables, the processing of the food in manufacturing facilities, and food cooking at home. Resveratrol has a reduced solubility in water, which affects its bioavailability, so its dissolution and absorption potential are low (Robinson et al., 2015). This implies that the main absorption occurs in the intestine and liver, where it is rapidly converted into primary metabolites (i.e., resveratrol sulfate and glucuronide) that are more easily excreted from the body, thus reducing the potential beneficial health effects (Pannu and Bhatnagar, 2019; Sergides et al., 2016). Another important aspect affecting the availability of resveratrol is the source used for its production, together with the amount of added dose, interaction with other substances (e.g., pharmaceuticals) and interindividual variation among consumers (Liu, 2022). To give an overview of the amount of resveratrol present in the most common vegetables and food products, as well as it methods for extraction and quantification, Table 2 is provided. Regarding the extraction technologies used, good recovery yields are attained with different techniques as summarized in Table 3. These techniques will be detailed in the next section. 4. From resources to product: main extraction techniques There are several methods for obtaining resveratrol, considering its extraction from plants and/or food products with different bioprocessing or chemical reaction schemes. Both conventional methods, such as solvent extraction, or emerging technologies, such as supercritical, microwave-assisted or ultrasound-assisted extraction, could be used as efficient procedures. Each method has its advantages and disadvantages, and the selection of one or the other will vary depending on the quality required, the desired processing time, and/or the type of raw material or resource used. In this context, this section highlights the most used extraction methods, both conventional and emerging, for resveratrol recovery. 4.1. Conventional methods Conventional extraction technologies have been used for resveratrol recovery from, for example, spruce bark. Diethyl ether was selected as the extraction solvent, with a solid-to-liquid ratio of 1:10, requiring an extraction time of 24 h. Then, as a subsequent step to purify resveratrol, a first washing step with 5 % sodium bicarbonate, elution in dichloromethane and methanol for a first HPLC analysis, followed by re-elution in dichloromethane and ethyl acetate for reverse-phase column chromatography, is necessary. Following this extraction scheme, an amount of 279.9 μ g of resveratrol/g spruce bark is obtained, thus achieving a global resveratrol recovery of 84 % (Piyaratne et al., 2022). Spruce species have also been used as feedstock for analyzing and identifying the best solvent to be used in the extraction of resveratrol compounds. This has been the main goal of Suprun et al. (2021) research, in which methanol, ethanol, ethyl acetate, acetone, hexane, and water were selected for resveratrol extraction (Suprun et al., 2021). Extraction temperatures, process time, and seasonal variation have also been evaluated, looking for the conditions that allow the highest possible extraction yield. The main results obtained showed that methanol is the most advisable solvent not only for resveratrol but also for other stilbene-based compounds (such as astringin, piceid, or piceatannol, among others). As for the operating conditions, 60 ◦C is the optimum temperature for resveratrol extraction from spruce bark, considering an extraction time of 6 h. Finally, as regards seasonal variation, it has been observed that the concentration of the target compound on the raw material really varies according to the harvesting season, detecting that, for resveratrol, autumn harvesting is the most suitable, whereas, when evaluating all the stilbene compounds, summer is the most recommended (Suprun et al., 2021). 4.2. Emerging methods Pressurized liquid extraction (PLE) has been used as an extraction method to recover the bioactive compounds available on grapevine shoots. Quercetin and resveratrol are the bio-actives extracted in gross quantity, being its concentrations in the grapevine shoots of 10.6 mg/g and 1.9 mg/g, respectively (Serna-Loaiza et al., 2022). It should be mentioned that quercetin is available mostly in the leaves, while resveratrol is mostly present in the stem part of the grapevine shoots, thus both could be obtained separately. The best results of extraction correspond to the following conditions: 75 ◦C and 50 vol% of ethanol, 30 min, and a solid load of 1:11 w/w. Considering these conditions, the extraction yield of resveratrol amounts to 1.90 mg/g dry matter of grapevine shoots, while for the case of quercetin the yield increases to 10.69 mg/g (Serna-Loaiza et al., 2022). Furthermore, the highest antioxidant capacity is obtained, thus increasing the quality of resveratrol and quercetin. On the other hand, a liquid hot water treatment could be applied to separate sulfur-free lignin from the cellulosic and hemicellulosic fractions of the grapevine shoots which could be used as a source of fermentable sugars, being a more efficient process scheme that valorizes completely the feedstock used (Serna-Loaiza et al., 2022). Another emerging green extraction technology that is considered for the extraction of stilbenes, such as resveratrol, is subcritical water extraction (SWE), requiring processing temperatures between 100 ◦C and 374 ◦C. The main advantage of this extraction alternative is that water at high temperature and pressure, acquires a dielectric constant similar to that of organic solvents, thus being able to extract the resveratrol within the same yield as the one achieved by ethanol. Vine pruning residue has been shown to be a relevant resveratrol source (Jesus et al., 2019, 2020). Jovanovi´ c Galovi´ c et al. (2022) have used SWE to extract trans-resveratrol from pruning waste of V. vinifera (vineyards) (Jesus et al., 2019), according to the following conditions: 200 ◦C, 30 bar, 18.27 min, addition of 1.55 of HCl, and a solid to liquid ratio of 1:10 g/mL (Jovanovi´ c Galovi´ c et al., 2022). Subsequently, a liquid extract was obtained with a flavonoid content of 2.91 g/100 g (dry weight, DW) and a phenolic content of 10.67 g/100 g (DW), with an amount of resveratrol extracted of 296.98 μ g/100 mL of extract (Jovanovi´ c Galovi´ c et al., 2022). Deep eutectic solvents have also been used as a green method for the extraction of resveratrol from different plant species, as Melinjo (Gnetum gnemon L.), a Gymnospermae with a promising composition of resveratrol. For the extraction, a NADES (natural deep eutectic solvent) has been prepared, for which various components are used: betaine:urea (1:11), betaine:lactic acid (1:1) and betaine:malic acid (1:1), 90 ◦C, 500 rpm and 90 min processing time. Afterward, the NADES is added to the Melinjo seed powder and ultrasound assisted extraction (UAE) is applied, with a solvent (water) to solid ratio of 1:10. Considering these aspects, the yield on resveratrol extraction amounts to 0.227 mg/g of powder, which is almost 50 % higher than using betaine-urea as extraction solvent and 70 % when using betaine-malic acid, which demonstrates the effectiveness of using NADES for the extraction of resveratrol (Aryati et al., 2020). A similar extraction procedure has been developed by Wang et al. (2021a, 2021b, 2021c), but using Polygonum cuspidatum, a Polygonaceae plant species, and using hydrogen bond donors for the formulation of the NADES, using glycerol and choline chloride/oxalic acid in a molar ratio of 1:1 and 75 ◦C. Afterward, NADES is mixed with P. cuspidatum powder in a ratio of 20 mg:1 mL and ultrasonicated for 80 min, prior to obtaining the final resveratrol product, within an extraction yield of 8.03 mg/g (Wang et al., 2021a, 2021b, 2021c). Chen et al. (2018a, 2018b) combined NADES with UAE for the extraction of resveratrol from peanut roots. The NADES is formulated considering choline chloride and 1.4-butanediol in a ratio of 1:3 g:g, requiring 55 ◦C, 40 min and a solid to liquid ratio of 1:30 g:mL. The UAE procedure requires energy (40 kHz and 400 W) to achieve a A. Arias et al. Science of the Total Environment 908 (2024) 168199 5 Table 2 Resveratrol amount, extraction or quantification method and important features on bibliographic references about resveratrol. Source Technique used Resveratrol amount Other information Reference Grapes Homogenization +HPLC 1.87 ±0.64 mg/g Digestibility: 52.45 ±3.48 (Lee et al., 2020) Water extraction +HPLC 1.47 ±0.26 mg/g Digestibility: 51.08 ±5.54 (Lee et al., 2020) Ethanol extraction +HPLC 1.97 ±0.71 mg/g Digestibility: 49.54 ±3.47 (Lee et al., 2020) Freeze drying +HPLC 7.93 ±2.05 μ g/g Red globe grape variety is the one with the higher resveratrol content (Wijekoon et al., 2022) Ethanol extraction +HPLC 4.74 ±3.57 mg/L Variability on content considering from July to September, being July the month in which the grapes have higher content (C˘ apruciu et al., 2022) Enzymatic hydrolysis with glycosidase and reverse-phase solid extraction 1.7 ±1.3 mg/L Variations on the concentration of resveratrol in function of the ripening stages, being 20◦Brix the one presenting the highest content (Genovese et al., 2021) Red wine Solid phase micro extraction 3.78 ±1.79 mg/L The average recovery obtained is 99.4 % (Aresta et al., 2018) HPLC 0.1–0.7 mg/L Resveratrol content in red wine improve insulin resistance and phosphorylation (Brasny´ o et al., 2011; Castaldo et al., 2019) HPLC 3.0 ±0.6 mg/kg Negroamaro red wine type (Salento) (Ragusa et al., 2019) HPLC 2.4 ±0.4 mg/kg Primitivo red wine type (Salento) (Ragusa et al., 2019) Reverse-phase HPLC 10.7 ±7.0 mg/L Decrease on an average of 76 % the resveratrol concentration during storage and wine ageing (Naiker et al., 2020) Red wine Homogenization, liquid-liquid microextraction and disperse solid-phase extraction 8–322 μ g/L Resveratrol content analysis of wines from local markets, detected in 4 out of 6 (Lu et al., 2018) Grape juice Solid phase micro extraction 0.74 ±0.22 mg/L The average recovery obtained is 94.9 % (Aresta et al., 2018) UltravioletC radiation and colorimetric analysis CP:0.53 ±0.06** OP:0.40 ±0.05** CP-UV:0.50 ±0.10** OP-UV:0.45 ±0.05** Comparison of traditional and organic productions, as well as UV posttreatment on resveratrol concentration (**mg/mL) (Pinto et al., 2022) Liquid-liquid 1 , ultrasound 2 and microwave assisted extraction 3 0.94 ±0.06 mg/kg 1 , ND 2 , 7.59 ±0.49 mg/kg 3 For conventional liquid-liquid extraction resveratrol is only detected with ethanol, and for MAE also with ethyl acetate, but 7 times lower in comparison with ethanol solvent (Pezzini et al., 2019) Folin – Ciocalteu colorimetric method 0.01 mg/ 100 g DW – 0.58 mg/100 g DW Grape juice coming from red wine is the one with highest resveratrol content, and the one coming from white wine has the lowest resveratrol content (Guler et al., 2022) Raisins Homogenization with HCl and methanol, and HPLC analysis 18.62 mg/kg 54 % of the antioxidant activity of raisins is coming from the content on resveratrol (Roychev et al., 2020) HPLC 1.08 ±0.17 mg/kg 4 and 0.40 ±0.04 mg/kg 5 Change on resveratrol content by raisins pre-treated with olive oil 4 and notpre-treated with olive oil 5 . (Olivati et al., 2019) Berries HPLC 236.4 ±7.5 μ g/g – 269.9 ±5.7 μ g/g The variety of blueberry implies different resveratrol concentration, and its degradation is increased when exposed to light at room temperature (Shanmuganathan and Li, 2009) HPLC 0.12 mg/100 g DPPH radical scavenging activity increases with the increase in resveratrol content (Song et al., 2014) Oleogel systems of soybean and peanut oil containing blueberry extract 0.001–0.063 mg/ 100 g Best inhibition rate for oxidation products achieved with soybean oleogel (Qiu et al., 2021) Ultrasound extraction with methanol as solvent 38.13 ±0.27 μ g/100 g dry matter The blueberry variety of “Windsor” is the one with higher resveratrol content, followed by “Millennia” variety (Varo et al., 2021) HPLC with 6 and without 7 ultraviolet treatment 2.43 mg/g 6 and 7.53 mg/g 7 dry weight Content of resveratrol on blueberry leaves, the UV irradiation increases the content of resveratrol (Kim et al., 2020) Extraction with 80 % acetone and dissolution with formic acid and methanol, HPLC 830.5 ±20.6 ng/ g of dry weight The concentration of resveratrol increases with maturation, with compost cultivation treatment and with enriched CO 2 environment (Wang et al., 2007) Cocoa & chocolate Botrytis inoculates to treat cocoa beans and treatment with UV light 7.0 g/g Enhancement of resveratrol content by modifying the treatment of the cocoa beans for the production of related products (Hurst et al., 2009) Extraction with ethanol/water for 10 min and 60 ◦C, analysis with HPLC 0.4 mg/kg in dark chocolate and 0.5 mg/kg in cocoa liquor The antioxidant activity of cocoa and chocolate is more related to the procyanidin content than the composition of stilbenes (Counet et al., 2006) Extraction with hexane, hydrolyzation with methanol/water acidified solution and rotatory evaporation before HPLC analysis 1.85 ±0.43 g/ g in cocoa powder, 0.35 ±0.08 g/g in dark chocolate, 0.10 ±0.05 g/g in milk chocolate The content of resveratrol on cocoa-related products varies according to the type of chocolate, the processing of the final product and the amount of contained sugar (Hurst et al., 2008) Industrial processing of chocolate for producing cocoarelated products 11.4 g/kg before fermentation and roasting and 9.8 g/kg after fermentation and roasting Fermentation and roasting processing stages imply a not significant reduction in the resveratrol content of cocoa-related products (Salvador et al., 2019) Peanut Ultrasonic and magnetic stirring-assisted dissolution 175.51 mg/kg peanut oil The resveratrol content of peanut oil helps to preserve its organoleptic and antioxidant properties, prolongs its shelf-life for 2 folds and improves its thermal stability. (Li et al., 2022) Peanut Ultrasonic treatment and phenylalanine addition during peanut germination 36.99 g/g dry weight The content of resveratrol by developing this alternative germination process increases 9.4 times (Yu et al., 2016) Various methods for drying peanuts for further resveratrol extraction: hot-air drying, infrared radiation and microwavefreeze-drying 33.5 % of resveratrol extracted using infrared radiation and 40.9 % using microwave The huge energy consumption of microwave-freeze-drying does not compensate the increased extraction capacity, being the infrared radiation the preferred drying method (Zhu et al., 2022) * CP: Conventional production, OP: organic production, UV: ultraviolet. A. Arias et al. Science of the Total Environment 908 (2024) 168199 6 resveratrol extraction yield of 38.91 mg of resveratrol per kg of peanut roots used (Chen et al., 2018a, 2018b). 5. Resveratrol production 5.1. Chemical synthesis The synthesis of resveratrol can be achieved following different Table 3 Extraction technologies for resveratrol recovery. Acronyms: PLE (Pressurized Liquid Extraction), SFE (Supercritical Fluid Extraction), SWE (Supercritical Water Extraction), DES (Deep Eutectic Solvents), NADES (Natural Deep Eutectic Solvents), UAE (Ultrasound Assisted Extraction). Method Product(s) Resource Operation conditions Recovery/yield Reference PLE Resveratrol (RES) and ellagic acid (EA) Blueberries 1500 psi 40 ◦C Methanol 91.85 % EA and 84.97 % RES Seyhan et al., 2023 PLE Trans-resveratrol Grapes 40 atm 5 min 150 ◦C Water 2.33 mg trans-RES /kg grapes, 94.5 % trans-RES Pi˜ neiro et al., 2006 PLE Resveratrol Grape seeds 1.02 MPa 152 ◦C 25 min Ethanol 1:15 g/mL 91.98 % Tian et al., 2017a, 2017b High pressure and high temperature stirred reactor Polyphenols Grape skins 150 ◦C 270 min Methanol 1:5 45.4 mg /100 g DS Casazza et al., 2012 SFE Resveratrol Grape skin 110 bar 40 ◦C 7.5 % ethane 15 min 100 % Pascual-Marti et al., 2001 SWE Resveratrol Bark 190 ◦C and 3 mL/min water flowrate 23.18 μ g/g dry weight Chainukool et al., 2014 SWE Resveratrol Grapevine 160 ◦C 5 min 10 MPa 1.95 g/kg dry mass Gabaston et al., 2018 DES Resveratrol Polygonum cuspidatum 80 ◦C 80 min 60 % v/v DES 4.5 % g/v HCl 40:1 g/mL 96.3 % Sun et al., 2021 NADES (choline chloride/oxalic acid) Resveratrol Polygonum cuspidatum 1:50 75 ◦C 80 min 250 W ultrasonic powder 12.31 mg/g Wang et al., 2021a, 2021b, 2021c DES +UAE Resveratrol Peanut roots 1:3 g water:g DES 55 ◦C 40 min 1:30 g/mL 88.19 % Chen et al., 2018a, 2018b Maceration Resveratrol Arachis repens 1:40 g: mL methanol 30 min 25 ◦C 1 h 1.02 mg/L Garcia et al., 2016 Solvent extraction Resveratrol and its glycoside Knotweed 35 ◦C 0.79 MPa 5 h Water 0.34 mg/g Kanda et al., 2021 Solvent extraction Resveratrol Grape skin Ethanol or methanol as solvent 1 h 1:10 80 ◦C 400 rpm stirring 72.4 mg/L MeOH and 71.3 mg/L EtOH, 82 % purity recovery TRIFOI and ANCUTA, 2019 Solid-liquid extraction Resveratrol and other phenolics Milled grape canes Ethanol/water (80:20 v/v) 30 min 83.6 ◦C 103.6 mg/L solvent to solid ratio 4.25 mg /g dw Karacabey and Mazza, 2008 Solvent extraction Trans-resveratrol Vine pruning waste 4:1 ethanol:diethyl ether 1 g: 35 mL solid to liquid ratio 96 h 25 ◦C 174.14 mg/kg dw Cr˘ aciun and Gutt, 2023 Liquid extraction Resveratrol Polygonum cuspidatum 2/3 v/v water/organic mixture 5 h 45 ◦C 81.10 % Wang et al., 2021a, 2021b, 2021c A. Arias et al. Science of the Total Environment 908 (2024) 168199 7 reaction schemes (Tian and Liu, 2020). The Heck-reaction is one the most widely used, consisting of a heterogeneous catalytic reaction in which a C-C cross-coupling is developed between a halide compound and an activated oleofin (Andrus et al., 2003; Klotter and Studer, 2014). Other common alternatives are the Perkin-reaction, characterized by the synthesis of unsaturated aromatic acids through the condensation of aromatic anhydrides and aldehydes (de Lima et al., 2009; Grau et al., 2023), and the Wittig-reaction, which comprises an oleofin production by the reaction between an aldehyde or a ketone with a primary or secondary alkyl halide (Chalal et al., 2012; Kang et al., 2009). Several studies also recurred to the Horner-Wadsworth-Emmons reaction, an organic reaction based on the reaction of a carbanion phosphate and an aldehyde or ketone (Gester et al., 2005; Khan et al., 2017). However, biosynthesis could be considered as an alternative more sustainable scheme. 5.2. Microbial synthesis Another valuable option that has attracted increasing interest among researchers is the microbial production of resveratrol. This has advantages over microbial-mediated conversion mainly due to the availability and cost of the resveratrol precursor. One example of such a process is the use of the bacteria Bacillus safensis to convert polydatin, a glucoside derivative of resveratrol, efficiently and rapidly to resveratrol, reaching a yield of 93.1 % in 8 h and 37 ◦C (Hu et al., 2019). Regarding resveratrol production, Escherichia coli and Corynebacterium glutamicum are, among bacteria, two of the most widely used hosts (Hong et al., 2020; Braga et al., 2018), while Yarrowia lipolytica, Scheffersomyces stipitis, and Saccharomyces cerevisiae are the most reported yeasts (Costa et al., 2021, 2022b; Kobayashi et al., 2021a, 2021b). Some strategies to increase the yield on resveratrol encompass protein engineering and mutagenesis of the microorganisms, increasing the overall efficiency and feasibility of the resveratrol production process. 5.2.1. Genetically modified strains Genetically engineered strains have been developed to enable the capacity of producing resveratrol. The first reports on the biotechnological production of resveratrol relied on the supply of the expensive precursor p-coumaric acid, which hindered the feasibility of the biotechnological production of resveratrol (Beekwilder et al., 2006). Since then, many developments were accomplished and, in the last decade, several studies on de novo resveratrol production from carbon sources were reported. The production of resveratrol from cheap and simple carbon sources, such as glucose or ethanol, by fed-batch fermentation has been proposed (100 h) and S. cerevisiae as a strain, achieving 415.65 mg/L of resveratrol from glucose and 531.41 mg/L from ethanol, being 5.7 and 3.1-fold higher compared to batch cultivation (Li et al., 2015). In fact, resveratrol production by fed-batch fermentation strategies has often been explored. In another study using a recombinant strain of S. cerevisiae, an initial concentration of 20 g/L glucose was used, with a subsequent feeding of 3 g/L/h, leading to a significant increase in resveratrol titers up to a final concentration of 4.1 ±0.2 g/L (Meng et al., 2023a, 2023b). While most of the researchers focus on using glucose as a carbon source, given the extensive number of feedstocks that could be used as a source of fermentable sugars, other carbon sources have also been explored to produce resveratrol. Park et al. (2021) engineered an E. coli strain with the ability to produce 80.4 mg/L of resveratrol using glycerol as a carbon source. S. stipitis, which is capable of naturally metabolizing various carbon sources, has been used to produce resveratrol from carbon sources such as glucose, fructose, galactose, xylose, maltose, and the disaccharides cellobiose and sucrose, reaching a maximum concentration of 668.6 mg/L from 50 g/L of sucrose (Kobayashi et al., 2021a, 2021b). Costa et al. (2022a, 2022b) have reported the production of resveratrol from lactose and xylose using recombinant S. cerevisiae strains, achieving titers of 210 mg/L and 223.8 mg/L of resveratrol, respectively. A maximum titer of 388 mg/L of resveratrol was achieved when combining xylose (10 g/L) and glucose (50 g/L) in batch fermentation. The authors reported the valorization of different agroindustrial residues such as cheese whey (source of lactose) or vine pruning residue hydrolysate (source of xylose and glucose) as substrates for resveratrol production (Costa et al., 2022a, 2022b; Kobayashi et al., 2021a, 2021b). 5.2.2. Co-culture production processes Other authors have also developed co-culture processes in order to enhance resveratrol production. Yuan et al. (2020) have developed a coculture of E. coli and S. cerevisiae, based on an upstream process in which E. coli can excrete p-coumaric acid for being used in the downstream module, in which S. cerevisiae is placed, with the function of converting p-coumaric acid into resveratrol. In this strategy, both upstream and downstream modules are fed with glucose as a carbon source of fermentable sugars (Yuan et al., 2020). Considering this co-culture, using an inoculation ratio of 1:1, 33.5 ◦C, and a process time of 72 h, the maximum amount of resveratrol obtained was 36 mg/L, representing a productivity of 0.25 mg/L/h. Hong et al. (2020) reported a coculture strategy using glucose as carbon source (20 g/L) and a single type microorganism, dividing this metabolic pathway in two E. coli strains. This co-culture was able to produce 55.7 mg/L of resveratrol after 30 h (Hong et al., 2020). 6. Examples of proposed biorefinery schemes The increase on the demands of agroindustrial-based products have ended on an intense production of waste streams, that, if not properly managed at the end of the value chain, could entail significant effects over the sustainability of the value chains. In this context, the enhancement and penetration of integrated biorefineries could promote eco-friendly and economically profitable production chains (De Corato et al., 2018). Resveratrol could be part of this transition on the implementation of integrated biorefineries, given the possibility of extracting or bioproducing it from waste resources with high carbon (sugar) composition. To this end, some examples of valorization scenarios are presented in this section. It should be noted that the later scenarios only include the section necessary for the extraction of resveratrol, which is included as another stage of the production process, i.e., in the wine production process, the grape pomace stream is valorized for the recovery of resveratrol. The idea of this section is to give a broader view of how the integration of waste streams to resveratrol production could help in the development of cascade biorefinery approaches, thus promoting the integral use of available resources. 6.1. Scenario I. Winery biorefinery The first stage of the winemaking process consists of destemming, in which the stems are removed from the grapes, thus being cataloged as the first waste stream obtained in the winemaking process with a significant concentration of resveratrol (0.08–5 mg/L) (Anastasiadi et al., 2012). This side stream could be considered as a potential bio-resource and two alternatives have been considered for providing an example of a biorefinery approach in the winery sector, depicted on Fig. 1. One conventional extraction technique and one emerging technology have been proposed, concretely maceration and pressurized liquid extraction (PLE). Both alternatives require a pre-treatment to dry the stems and reduce their size through a crushing stage, before passing thoroughly to the extraction stage. In the case of maceration, a solid/ liquid ratio of 1:100 w/v is required, using ethanol at 50 % as solvent. One of the main drawbacks in performing maceration is the extraction time required (24 h), somewhat decreasing the resveratrol productivity. Considering these operation conditions, and a constant temperature of 40 ◦C, the recovery of resveratrol amounts to 0.88 mg/g extract (Quero et al., 2021). In the case of opting for PLE, the solvent required is barely A. Arias et al. Science of the Total Environment 908 (2024) 168199 8 the same, considering in this case a ratio of 30 % v/v. The main difference observed on the extraction conditions relies on the extraction time (only 10 min), and on the temperature, which is significantly higher (120 ◦C). The amount of resveratrol obtained by the development of the PLE method is 227 mg/g of stalks (DW) going through the extraction reactor, thus being a potential valorization route for the residual stalks (Nieto et al., 2020). Grape skins and pips are another by-product obtained in the industrial production of wine, with 120 kg of this waste stream being obtained per ton of grapes (Marqu´ es et al., 2013; Rodrigues et al., 2022). Given this large amount of residual secondary flow produced, the recovery of the available bioactive compounds, such as resveratrol, could be considered as a viable and an appropriate strategy in search of a more sustainable wine production. In this regard, two main alternatives for resveratrol extraction have been included in Fig. 1. One possible route for extracting the resveratrol from grape skin and seeds is through conventional extraction, using as solvent a mixture of methanol/HCl, requiring 30 min of process time, to be afterward centrifuged and filtered for further purification. Another alternative is an extraction procedure at high pressure, using as CO 2 and ethanol as solvents, requiring 400 bar and 55 ◦C. The main difference between both extraction technologies relies on the extraction yields and the concentration of resveratrol in the extract. While for the conventional extraction a yield of 0.9 mg resveratrol/100 g of dry sample and a concentration of 8.82 mg resveratrol/g extracted is obtained, by using a high pressurization system the yield increases to 19.2 mg resveratrol/ 100 g of dry sample and the concentration to 5.97 mg resveratrol/g extracted, thus enable a more efficient production process to be further scaled-up (Casas et al., 2010). A similar result has been obtained by Monari et al. (2020), who also chose to compare a solvent extraction, in this case with ethanol, and a pressurized liquid extraction, with the latter showing a higher extraction yield. Another more emerging technology is the supercritical water extraction, requiring firstly an air drying and grinding pretreatment of the seeds and grape skin. It consists of a high pressure and temperature extraction procedure, amounting to 1 MPa and 152 ◦C, respectively, with a solid-to-liquid ratio of 1:15 g/mL, requiring an extraction time of 25 min. Bearing in mind these operation conditions, a total of 6.9 μ g resveratrol/g extract was obtained, which is a lower quantity in comparison with the high pressure and temperature extraction method, though the process time is lower. Considering an analogous time for extraction, the total quantity of resveratrol that could be potentially extracted is 49.6 μ g resveratrol/g (Tian et al., 2017a, 2017b). Finally, the third residual stream obtained is the result of the aging and wine stabilization stage, being known as the wine lees, concretely defined by the EEC regulation No. 337/79 as “residue formed at the bottom of wine containers after fermentation, during storage or after treatments, as well as the one obtained after filtration or centrifugation of wine”. The wine aging is the main stage of wine manufacturing responsible for the production of these residual streams and, in fact, this is a traditional technique that improves the quality of wines, as its lees are able to enhance the structure and color stability of the wine products (Jara-Palacios, 2019). Two strategies have been considered, the first one based on the extraction of resveratrol, and the second one based on the production of the resveratrol using a recombinant S. cerevisiae strain (Fig. 1). Regarding the extraction procedure, the ultrasonic assisted extraction requires a pretreatment of the wine lees with ethanol 50 % (v/v) and formic acid 1.55 % (v/v) in order to enhance the productivity of the extraction stage and considering a solid to liquid ratio of 1:60 (w/v). Afterward, the pretreated wine lees undergo the extraction stage, requiring a ultrasonic power of 400 W and an amplitude of 90 %, for an extraction time of 25 min, to obtain a yield on resveratrol that amounts to 0.11 mg/g dry weight of wine lees (Dujmi´ c et al., 2020). On the other hand, by considering a bioproduction process, sterilization and sonication of wine lees is required as pretreatment stage before introducing them into the fermenter. The concentration of yeast extract required for the fermentation process is 7.5 g/L, and the wine lees are dissolved in the fermentation media to achieve a concentration value of 50 % (v/v). After 96 h of fermentation time, the quantity of resveratrol obtained amounts to 263.9 mg/L, which could be considered as a potential alternative for resveratrol production, partly due to the avoidance of polluting solvents and the use of renewable biological resources for resveratrol production (Costa et al., 2022a). 6.2. Scenario II. Peanut skin biorefinery Peanut skin is a by-product obtained from peanut processing, with a global average production of 46 million tons annually, and, for the moment, is a scarcely explored source of antioxidants of biological origin (Putra et al., 2023). Its commercialization in the market is not foreseen at the moment, given its high tannin content and low caloric level (Lorenzo et al., 2018). On the other hand, their high level of antioxidants and other bioactive compounds opens up a possibility for their valorization through recovery extraction processes (Sorita et al., 2020). One of the most commercialized products from peanuts, apart from its natural and roasted form, is peanut butter. For this section, a simple biorefinery flowchart is provided in the framework of integrating resveratrol recovery into the peanut butter processing line (Fig. 2). Jin et al. (2020) have developed an extraction of resveratrol by the Fig. 1. Biorefinery alternatives for the valorization of wine production side-streams to resveratrol. A. Arias et al. Science of the Total Environment 908 (2024) 168199 9 combination of ultrasound-assisted surfactant extraction and microbial immobilization using cellulose. A combined consortium of yeast and Aspergillus sp., namely, Aspergillus oryzae and Aspergillus niger, has been considered the best microbial combination to enhance the recovery of resveratrol from peanut skin wastes. In order to immobilize the microbial cells, a cellulose gel was prepared using sterile cotton, water, NaOH and urea, requiring soaking for 2 h at −20 ◦C, to be subsequently sterilized for use in the extraction step. Additionally, it is also necessary to add a surfactant, as it helps to maintain the stability of the enzyme, thus helping to achieve a higher extraction yield. In this case, the use of Triton X-114 is the one preferred, with a concentration of 3 % (w/v), a nonionic surfactant, non-toxic and cheap, leading to an extraction yield of 96.58 μ g/g. Regarding the extraction conditions, a temperature of 30 ◦C, an ultrasonic power of 250 W, a ratio of 25:1 mL/g, and a process time of 36 h are the optimal conditions for achieving the highest amount of resveratrol (96.58 μ g/g), which is 4-fold higher when compared to a traditional extraction method (Jin et al., 2020). Syahdi et al. (2020) have used NADES in combination with ultrasound-assisted extraction (UAE) or microwave-assisted extraction (MAE) to obtain resveratrol, in order to compare the yields obtained with a conventional extraction technique, such as maceration, which requires a larger amount of solvent and a longer extraction time (Syahdi et al., 2020). Regarding the model of extraction used, the MAE requires the addition of 70 % ethanol as solvent, a processing time of 12 h at 23 ◦C, and a microwave power that amounts to 270 W. In the case of UAE, the NADES is prepared using choline chloride and oxalic acid, in a molar ratio of 1:1, as it is the combination that promotes the higher resveratrol extraction, and is used as the solvent for UAE, considering a solid to NADES ratio of 1:20 (g:mL) and 15 min of process time. By assessing those alternatives, the use of UAE combined with NADES is the one achieving a higher extraction of resveratrol of 0.049 mg/g dry weight (0.011 mg/g DW), but when compared to the conventional extraction method by maceration, the yield is significantly lower, reaching a total of 0.221 mg/g (DW). However, taking into account that maceration requires an extraction time of 24 h, the total amount of resveratrol produced amounts to 4.70 mg, being thus significantly higher (Syahdi et al., 2020). Therefore, it can be concluded that UAENADES is an efficient and more sustainable technology for the recovery of resveratrol from peanut skin waste and is a potential alternative to be integrated in a biorefinery. <Fig. 2 to be included here> 6.3. Scenario III. Wood bark biorefinery The commercialization and production of wood-based products, such as wood panels or furniture, has increased intensively in the last decades (Arias et al., 2022). The main residual stream obtained from the production process is the bark, as debarking is one of the first stages required for wood-based panels and related wood products, including the pulp and paper industries. In this regard, it is estimated that millions of cubic meters of bark are annually managed as residues (Gomes et al., 2021). The valorization strategies of these waste streams are usually based on energy production, through their combustion, but prior to this end-of-life management strategy, the extraction of the valuable compounds could be considered in the arena of circular economy (Andersone et al., 2018). Given its composition on resveratrol, wood bark could be considered as a potential bio-based resource for the development of an integrated biorefinery producing resveratrol as a side-product (Fig. 3). In addition, this extraction could be integrated with the simultaneous valorization of the remaining bark to biofuels (Romaní et al., 2019). Regarding the extraction alternatives for resveratrol recovery, Ferreira-Santos et al. (2020) have considered developing a conventional solid-to-liquid extraction to extract the phenolic compounds available in the bark, including resveratrol (Ferreira-Santos et al., 2020). The extraction conditions require 115 min of process time, 82 ◦C and with a solid-to-liquid ratio of 0.15 g/mL, using ethanol 70 % (v/v) as solvent, thus obtaining a concentration of resveratrol that amounts to 18.9 mg/L (Ferreira-Santos et al., 2020). Jyske et al. (2022) have reported the extraction of resveratrol from spruce bark by developing a conventional hot extraction method, based on using a solution of acetone:water 95:5 (v/v) as solvent, with a concentration of 0.2 mg/L, in an ultrasonic batch for 30 min, thus obtaining a concentration of resveratrol that amounts to 22 mg/g of dry weight (Jyske et al., 2022). Fig. 2. Biorefinery alternative of peanut processing considering resveratrol extraction from peanut peels. A. Arias et al.