*Review* **Phytochemicals Derived from Agricultural Residues and Their Valuable Properties and Applications**

**Marta Oleszek 1,\* , Iwona Kowalska <sup>1</sup> , Terenzio Bertuzzi <sup>2</sup> and Wiesław Oleszek <sup>1</sup>**


**Abstract:** Billions of tons of agro-industrial residues are produced worldwide. This is associated with the risk of pollution as well as management and economic problems. Simultaneously, nonedible portions of many crops are rich in bioactive compounds with valuable properties. For this reason, developing various methods for utilizing agro-industrial residues as a source of high-value by-products is very important. The main objective of the paper is a review of the newest studies on biologically active compounds included in non-edible parts of crops with the highest amount of waste generated annually in the world. The review also provides the newest data on the chemical and biological properties, as well as the potential application of phytochemicals from such waste. The review shows that, in 2020, there were above 6 billion tonnes of residues only from the most popular crops. The greatest amount is generated during sugar, oil, and flour production. All described residues contain valuable phytochemicals that exhibit antioxidant, antimicrobial and very often anti-cancer activity. Many studies show interesting applications, mainly in pharmaceuticals and food production, but also in agriculture and wastewater remediation, as well as metal and steel industries.

**Keywords:** bioactive compounds; antioxidants; agricultural residues; fruits; vegetables; mass spectrometry; extraction

### **1. Introduction**

The agricultural industry generates billions of tonnes of waste from the tillage and processing of various crops. The crops with the largest amounts of produced residues are rice, maize, soybean, sugarcane, potato, tomato, and cucumber, as well as some fruits, mainly bananas, oranges, grapes, and apples [1,2]. It has been estimated that European food processing companies generate annually approximately 100 Mt of waste and by-products, mostly during the production of drinks (26%), dairy and ice cream (21.3%), and fruits and vegetables (14.8%) [3].

In Table 1, the amounts of particular wastes generated worldwide are presented. Many of them are rich in biologically active compounds and have the potential to become important raw materials for obtaining valuable phytochemicals. Vegetable and fruit processing by-products are promising sources of valuable phytochemicals having antioxidant, antimicrobial, anti-inflammatory, anti-cancer, and cardiovascular protection activities [4]. The applications of these agro-industrial residues and their bioactive compounds in functional food and cosmetics production were presented in many studies [5–7]. Moreover, due to the potential health risk of some synthetic antioxidants such as BHA, the identification and isolation of natural antioxidants from waste has become increasingly attractive. Important criteria to decide if a product or by-product can be of interest to recover phytochemicals are the absolute concentration and preconcentration factor, as well as the total amount of product or by-product per batch [8].

**Citation:** Oleszek, M.; Kowalska, I.; Bertuzzi, T.; Oleszek, W. Phytochemicals Derived from Agricultural Residues and Their Valuable Properties and Applications. *Molecules* **2023**, *28*, 342. https:// doi.org/10.3390/molecules28010342

Academic Editors: Stefano Castellani and Massimo Conese

Received: 1 December 2022 Revised: 21 December 2022 Accepted: 25 December 2022 Published: 1 January 2023

**Copyright:** © 2023 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/).



well as the total amount of product or by-product per batch [8].

recover phytochemicals are the absolute concentration and preconcentration factor, as

*Molecules* **2023**, *28*, 342 2 of 51

\* based on FAOSTAT, 2022, \*\* calculated based on the global crop production in 2020 and the residue-to-crop ratio according to cited references. \* based on FAOSTAT, 2022, \*\* calculated based on the global crop production in 2020 and the residue-to-crop ratio according to cited references.

As interest in waste processing has been growing in recent years, many scientific papers have been published on new compounds in agro-industrial waste, new properties of valuable phytochemicals contained in crop residues and their applications. It seems necessary to summarize and collect the latest knowledge on this subject. In this work, an overview of the recent knowledge on the phytochemicals in some of the most popular food by-products, with the highest amount generated in the world, as well as on their properties and potential applications, have been presented in more detail (Figure 1). As interest in waste processing has been growing in recent years, many scientific papers have been published on new compounds in agro-industrial waste, new properties of valuable phytochemicals contained in crop residues and their applications. It seems necessary to summarize and collect the latest knowledge on this subject. In this work, an overview of the recent knowledge on the phytochemicals in some of the most popular food by-products, with the highest amount generated in the world, as well as on their properties and potential applications, have been presented in more detail (Figure 1).

**Figure 1.** Agricultural residues and the properties and applications of their phytochemicals. **Figure 1.** Agricultural residues and the properties and applications of their phytochemicals.

#### **2. Phytochemicals from Crop Residues**

#### *2.1. Sugarcane Bagasse*

Large amounts of waste are generated during the processing of sugarcane. In fact, one metric ton of sugarcane generates 280 kg of bagasse. Sugarcane bagasse is one of the most abundant agro-food by-products and is a very promising raw material available at low cost for recovering bioactive substances [18,19]. Sugarcane bagasse consists mainly of cellulose (35–50%), hemicellulose (26–41%), lignin (11–25%), but also some amount of plant secondary metabolites (PSM), mainly anthocyanins and mineral substances [20–25].

Phenolic compounds are a very important group of natural substances identified in sugarcane waste. Nonetheless, steam explosion and ultrasound-assisted extraction (UAE) pretreatment was applied for the production of valuable phenolic compounds from the lignin included in this residue. Chromatographic analysis revealed that sugarcane bagasse is a good feedstock for the generation of phenolic acids. The concentration of total phenolics with the Folin-Ciocalteau method was between 2.8 and 3.2 g/L. Zhao et al. [26] have identified many phenolics, mainly flavonoids and phenolic acids, in sugarcane bagasse extract (Table 2). The total polyphenol content was detected as higher than 4 mg/g of dry bagasse, with total flavonoid content of 470 mg quercetin/g of polyphenol. The most abundant phenolic acids identified in the sugarcane bagasse extract were gallic acid (4.36 mg/g extract), ferulic acid (1.87 mg/g extract) and coumaric acid (1.66 mg/g extract). Spectroscopic analysis showed that a predominant amount of *p*-coumaric acid is esterlinked to the cell wall components, mainly to lignin. On the other hand, about half of the ferulic acid is esterified to the cell wall hemicelluloses. The purified sugarcane bagasse hydrolysate consisted mainly of *p*-coumaric acid. Besides, the purified products showed the same antioxidant activity, reducing power and free radical scavenging capacity as the standard *p*-coumaric acid. Al Arni et al. [27] stated that the major natural products contained in the lignin fraction were *p*-coumaric acid, ferulic acid, syringic acid, and vanillin.


**Table 2.** Phytochemicals derived from sugarcane bagasse.


**Table 2.** *Cont.*

\* MW—molecular weight.

Gallic, coumaric, caffeic, chlorogenic, and cinnamic acids were the main phenolic compounds extracted from raw and alkaline pretreated sugarcane bagasse and identified by high-performance liquid chromatography (HPLC) [28]. The aromatic phenolic compounds (*p*-coumaric acid, ferulic acid, *p*-hydroxybenzaldehyde, vanillin, and vanillic acid) were reported in sugarcane bagasse pith. Five phenolic compounds (tricin 4-*O*-guaiacylglyceryl ether-7-*O*-glucopyranoside, genistin, *p*-coumaric acid, quercetin, and genistein) in 30% hydroalcoholic fraction of sugarcane bagasse were identified using ultra-high performance liquid chromatography/high-resolution time of flight mass spectrometry (UHPLC-HR-TOF-MS); (Table 2). The total phenolic content was 170.68 mg gallic acid/g dry extract [19].

Phenolic compounds derived from sugarcane bagasse exhibited many biological activities, which were used in various applications. The most important biological activities and the newest and most interesting applications have been summarized in Table 3.


**Table 3.** Biological activities and potential applications of phytochemicals obtained from sugarcane bagasse.

#### *2.2. Maize Residues*

Maize (corn *Zea mays* L.) bran, husk, cobs, tassel, pollen, silk, and fiber are residues of corn production. They contain substantial amounts of phytochemicals, such as phenolic compounds, carotenoid pigments and phytosterols [39] (Table 4).



Corn bran is produced as a plentiful by-product during the corn dry milling process. Similar to other cereal grains, phenolics in corn bran exist in free insoluble bound and soluble-conjugated forms. Corn bran is a rich source of ferulic acid compared to other cereals, fruits and vegetables. Guo et al. [39] isolated four forms of ferulic acid and its derivates from corn bran. On the other hand, it has been reported that the hexanederived extract from corn bran contains high levels of ferulate-phytosterol esters, similar in composition and function to oryzanol.

Another corn waste is a husk. It is the outer leafy covering of an ear of *Zea mays* L. The main constituents of the maize husk extracts determined in various phytochemical studies are phenolic compounds, e.g., flavonoids [41,50]. Saponins, glycosides, and alkaloids are present mainly in the aqueous and methanolic extracts, while phenols and tannins are numerous in methanolic ones [51]. Moreover, corn husk has high contents of anthocyanins [48,52]. Simla et al. [53] reported that anthocyanins concentration in corn husks ranges from 0.003 to 4.9 mg/g. The major anthocyanins of corn husk were identified as malonylation products of cyanidin, pelargonidin, and peonidin derivatives [54].

Important by-products of the corn industry are cobs. For every 100 kg of corn grain, approximately 18 kg of corn cobs are produced. Corn cob is one of the food wastematerial having a phytochemical component that has a healthy benefit [55]. They contain

cyanidin-3-glucoside and cyanidin-3-(600malonylglucoside) as main anthocyanins, as well as pelargonidin-3-glucoside, peonidin-3-glucoside and their malonyl counterparts [48].

Corn tassel is a by-product from hybrid corn seed production and an excellent source of phytochemicals (the flavonol glycosides of quercetin, isorhamnetin and kaempferol) with beneficial properties [56]. In Thailand, purple waxy corn is considered a special corn type because it is rich in phenolics, anthocyanins, and carotenoids in the tassel [57]. Besides, corn tassels could be considered a great source of valuable products such as volatile oils.

Corn pollen is another corn waste. Significant amounts of phytochemicals, including carotenoids, steroids, terpenes and flavonoids, are present in maize pollen [52]. Bujang et al. (2021) showed that maize pollen contains a high total phenolic content and total flavonoid content of 783.02 mg gallic acid equivalent (GAE)/100 g and 1706.83 mg quercetin equivalent (QE)/100 g, respectively. The flavonoid pattern of maize pollen is characterized by an accumulation of the predominant flavonols, quercetin and traces of isorhamnetin diglycosides and rutin. According to Žili´c et al. [58], the quercetin values in maize pollen were 324.16 µg/g and 81.61 to 466.82 µg/g, respectively.

Corn silk, another by-product from corn processing, contains a wide range of bioactive compounds in the form of volatile oils, steroids, saponins, anthocyanins [59], and other natural antioxidants, such as flavonoids [52] and phenolic compounds [41,58,59]. In the corn silk powder, the high phenolic content (94.10 ± 0.26 mg GAE/g) and flavonoid content (163.93 ± 0.83 mg QE/100 g) are responsible for its high antioxidant activity [60]. About 29 flavonoids have been isolated from corn silk. Most of them are C-glycoside compounds and have the same parent nucleus as luteolin [44]. Ren et al. [61] successfully isolated and separated compounds such as 200 -*O*-*α*-L-rhamnosyl-6-C-300-deoxyglucosyl-3 0 -methoxyluteolin, ax-50 -methane-30 -methoxymaysin, ax-400-OH-30 -methoxymaysin, 6,40 dihydroxy-30 -methoxyflavone-7-*O*-glucoside, and 7,40 -dihydroxy-30 -methoxyflavone-200 - *O*-*α*-L-rhamnosyl-6-C fucoside from corn silk. Moreover, among flavonoids, Haslina and Eva [43] determined in corn silk: apigmaysin, maysin, isoorientin-200 -*O*-*α*-L-rhamnoside, 3-methoxymaysine, and ax-4-OH maysin.

This richness of biologically active compounds results in advantageous properties and applications. The most important properties and the newest studies on the application are listed in Table 5.


**Table 5.** Biological activity and potential applications of phytochemicals obtained from corn wastes.

#### *2.3. Potato Waste*

Approximately 40–50% of potatoes are not suitable for human consumption. Industrial processing of potatoes (mashed and canned potatoes, chips, fries and ready meals) creates

huge amounts of peel as waste [66,67]. Potato peel is a non-edible residue generated in considerable amounts by food processing plants. Depending on the peeling process, e.g., abrasion, lye or steam peeling, the amount of waste can range between 15 and 40% of the number of processed potatoes [68]. Industrial processing produces between 70 to 140 thousand tons of peels worldwide annually, which are available to be used in other applications [69].

Potato peels differ greatly from other agricultural by-products because they are revalorized as a source of functional and bioactive compounds, including phenolic compounds, glycoalkaloids, vitamins and minerals [70] (Table 6).


**Table 6.** Phytochemicals identified in potato waste.

Potato peel is a good source of phenolic compounds because almost 50% of potato phenolics are located in the peel and adjoining tissues [74,83]. The results obtained by Wu et al. [77] showed that the potato peels contained a higher amount of phenolics than the flesh. Moreover, the polyphenols in potato peel are ten times higher than those in the pulp. Potato peel extract contains 70.82 mg of catechin equivalent (CE)/100 g of phenolic and had a high level of phenolic compounds (2.91 mg GAE/g dry weight) that was found to be greater than carrot (1.52 mg GAE/g dry weight), wheat bran (1.0 mg GAE/g dry weight), and onion (2.5 mg GAE/g dry weight) [67]. The results of Javed et al. [72] showed that the total phenolic content in potato peel ranged from 1.02 to 2.92 g/100 g and

total flavonoids ranged from 0.51 to 0.96 g/100 g. Phenolic acids are the most abundant phenolic compounds in potato peel. They include derivatives of hydroxycinnamic and hydroxybenzoic acids (Table 6). Kumari et al. [84], using UHPLC-MS/MS, showed that chlorogenic and caffeic acids are important components of the free-form phenolics in potato peel. The results show that phenolic acids in potato peals are not only present in their free form but also occur in bound form. Javed et al. [72] showed that the extract of potato peel contains chlorogenic acid (753.0–821.3 mg/100 g), caffeic acid (278.0–296.0 mg/100 g), protocatechuic acid (216.0–256.0 mg/100 g), *p*-hydroxybenzoic acid (82.0–87.0 mg/100 g), gallic acid (58.6–63.0 mg/100 g), vanillic acid (43.0–48.0 mg/100 g), and *p*-coumaric acid (41.8–45.6 mg/100 g). Silva–Beltran et al. [78] showed that flavonoids such as rutin and quercetin were present in potato peel at low concentrations of 5.01 and 11.22 mg/100 g dry weight, respectively.

Many studies have noted that potato peels are excellent untapped source of steroidal alkaloids, e.g., glycoalkaloids (*α*-solanine and *α*-chaconine) and aglycone alkaloids (solanidine and demissidine; Table 6) [80,81,85]. *α*-solanine, *α*-chaconine, and the glycosides of solanidine constitute about 95% of the total potato peel glycoalkaloid content [86]. Higher amounts of these compounds were found in potato peel, unlike potato flesh [87]. There are various cultural, genetic and storage factors that influence the concentration of glycoalkaloids in potato peel [88]. Concerning cultivars, it was shown that the variety with blue flesh showed the highest concentration (5.68 mg/100 g fresh weight), followed by the red-leaved (5.26 mg/100 g fresh weight), while yellow or cream flesh. In the study of Singh et al. [89] of potato peel, glycoalkaloids were detected as 1.05 mg/100 g. The results of Rytel et al. [88] showed that the glycoalkaloid content of potato peel depends on the potato cultivar and ranges from 181 mg/kg to 3526 mg/kg of fresh potato tubers.

Besides, the peel of pigmented potatoes is an excellent source of anthocyanins, e.g., pelargonidin-3-(*p*-coumaryoly rutinoside)-5-glucoside and petunidin-3-(*p*-coumaroyl rutino side)-5-glucosid e. It has been proven that their content depends on the cultivar [90]. Ji et al. [80] showed that anthocyanidin levels were higher in the peel than in the tuber. The most important beneficial properties and potential applications of phytochemicals identified in potato waste are listed in Table 7.


**Table 7.** Biological activity and potential applications of phytochemicals obtained from potato wastes.


#### **Table 7.** *Cont.*

#### *2.4. Soybean Residues*

Soybean waste has the potential as a sustainable source of phytochemicals and functional foods. It includes both leaves, pod pericarp, and twigs, as well as the residues after seeds processing, so-called okara. Okara is the residue of soybean milling after extraction of the aqueous fraction used for producing tofu and soy drink and presents high nutritional value [109]. The results of the last studies showed that an okara contains enough bioactive compounds that make it useful to obtain value-added products for use in food production, oil extraction, nutraceutical, pharmaceutical, and cosmetic formulations. Moreover, it was stated that okara isoflavones have good antioxidant activity. Although some nutrients like protein decrease in okara during soymilk processing, it still has many other phytochemicals and nutrients, making it their least expensive and most excellent source. Since it has good antimicrobial activity, it can be used in pharmaceutical industries, thus opening up new frontiers for drug exploration [109]. Various food enriched with okara, such as biscuits and cookies, have been mentioned in the literature [110,111]. Guimarăes et al. [112] reported that food products enriched with okara contained 0.411 mg/100 mL of *β*-carotene and 0.15 µm/g isoflavones.

One of the main phytochemicals in soybean waste are isoflavones: daidzein, genistein, glycitein, and their glycosides (e.g., acetyl-, malonyl-, and *β*-glycosides) [113]. Isoflavones are compounds belonging to the flavonoid group. In addition to the well-established antioxidant effect, isoflavones exhibit estrogenic activity because of their similar structure to estrogen [113,114]. The beneficial effects of isoflavones are the prevention of hormonedependent cancer, coronary heart disease, osteoporosis, and menopausal symptoms [114]. Kumar et al. [115] proved that daidzein expressed anticancer activity against human breast cancer cells MCF-7. The extract from soybean waste material showed total phenolic content (TPC) in the range of 27.4–167 mg GAE/g, total flavonoids from 10.4 to 63.8 mg QE/g and antioxidant activity (AOA) from 26.5% to 84.7% [114]. Moreover, their values were highest in the leaves, followed by pod pericarp and twigs. As was stated by Šibul et al. [113], soybean roots are also a good source of daidzein and genistein, as well as other phenolic compounds. The concentrations of isoflavones in roots were higher than in herbs, 1584.5 and 93.48 µg/g of dry extract, respectively. The newest study on soybean pods stated that

its ethanolic extract and fractions exhibited anticancer potential against human colorectal carcinoma (HTC-116) and prostate cancer (PC-3) [116]. Moreover, it was the first analysis of this material using ultra-*high*-*performance liquid chromatography* coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS), resulting in the identification of 50 polyphenols belonging to phenolic acids, flavonoids and other groups. The authors stated that soybean pods might be useful material as an active food additive or a component in dietary supplements and preparations with anti-radical and anti-cancer properties.

Soybean by-products are a good source of lecithin. Lecithin is a natural emulsifier that stabilizes fat and improves the texture of many food products, such as salad dressings, desserts, margarine, chocolate, and baking and cooking goods [117]. Moreover, it also has health benefits such as lowering cholesterol and low-density lipoprotein level in the human blood, improving digestion, cognitive and immune function, as well as aiding in the prevention of gall bladder and liver diseases.

Saponins are another important group of phytochemicals derived from soybean waste [113]. Soyasaponins have been linked to anti-obesity, antioxidative stress, and anti-inflammatory properties, as well as preventive effects on hepatic triacylglycerol accumulation [118]. One of the latest applications of saponins derived from soybean byproducts was as eco-friendly agents for washing pesticide residues in the vegetable and fruit industries [119].

Compounds identified and quantified in soybean waste are specified in Table 8. The newest studies on the applications and properties of soybean waste are presented in Table 9.


**Table 8.** Phytochemicals identified and quantified in soybean waste.


#### **Table 8.** *Cont.*


#### **Table 8.** *Cont.*

a

expressed in mg per kg of dry extract, <sup>b</sup> depending on cultivar, <sup>c</sup> expressed in mg per kg of residues.

**Table 9.** Biological activity and potential applications of phytochemicals obtained from soybean residues.


#### *2.5. Tomato Residues*

During the industrial processing of tomatoes, a considerable amount of waste is generated. Tomato waste consists mainly of peel, seeds, stems, leaves, fibrous parts and pulp residues [124]. The wet tomato pomace constitutes the major part of this waste, which consists of 33% seed, 27% peel and 40% pulp, while the dried pomace contains 44% seed and 56% pulp and peel [125]. When tomatoes are processed into products like ketchup, juice or sauces, 3–7% of their weight becomes waste. The management of tomato by-products is considered an important problem faced by tomato processing companies due to their disposal into the environment [126,127].

Although tomato waste has no commercial value, it is a rich source of nutrients, colorants and highly biologically active compounds such as polyphenols, carotenes, sterols, tocopherols, terpenes, and others (Table 10) [128–132]. The number of these compounds depends on tomato variety, part of the tomato residues (seed, peels, and pulp), time and extraction method, used solvent, as well as fractions gained after the isolation procedure, e.g., alkaline-hydrolyzable, acid-hydrolyzable, and bound phenolics [133]. They reported a total phenolics average of 1229.5 mg GAE/kg, of which flavonoids accounted for 415.3 mg QE/kg. The most abundant phenolic acids quantified in dried tomato waste were ellagic (143.4 mg/kg) and chlorogenic (76.3 mg/kg) acids. Other phenolic acids determined in lower concentrations were gallic, salicylic, coumaric, vanillic and syringic [133]. The levels of vanillic (26.9 mg/kg) and gallic (17.1 mg/kg) was lower than those found by Elbadrawy and Sello [134] in tomato peel (33.1 and 38.5 mg/kg, respectively). Cetkovi´c ´ et al. [135] identified phenolic acids (chlorogenic, *p*-coumaric, ferulic, caffeic and rosmarinic acid), flavonols (quercetin and rutin and its derivatives), and flavanone (naringenin derivatives) as the major phenolic compounds in extracts of tomato waste. The results obtained by Aires et al. [136] showed that the major polyphenol found in tomato wastes were kaempferol-3-*O*-rutinoside and caffeic acid. Several papers [135–138] reported the amounts of caffeic, chlorogenic, *p*-coumaric acids, kaempferol and quercetin, among other phenolic compounds found in tomato by-products. In the tomato's wastes, Di Donato et al. [139] identified two main flavonoid compunds e.g., kaempferol rutinoside and quercetin rutinoside. Rutin and chlorogenic acid were the most abundant individual phenolics found by García–Valverde et al. [140] in all studied tomato varieties.

**Table 10.** Phytochemicals identified in tomato wastes.



Traditionally, the bioactivity of tomatoes and their products has been attributed to carotenoids (*β*-carotene and lycopene). The results of Nour et al. [133] confirmed that dried tomato wastes contain considerable amounts of lycopene (510.6 mg/kg) and *β*-carotene (95.6 mg/kg) and exhibited good antioxidant properties. The results obtained by Fărca¸s et al. [145] confirmed lycopene as the main carotenoid of tomato waste in a concentration between 42.18 and 70.03 mg/100 g DW (dry weight). Simultaneously, peels contain around 5 times more lycopene compared to tomato pulp [146,147]. The lycopene content in peel was 734 µg/g DW, but significant amounts of *β*-carotene, cis-*β*-carotene and lutein were also determined. The study by Górecka et al. [148] showed that tomato waste could be considered a promising source of lycopene for the production of functional foods.

Peels, as one of the main residues of tomato, are a richer source of nutrients and biologically active compounds than the pulp [137,149]. Despite of high concentration of carotenoids, peels also contain a considerable amount of polyphenols. The results obtained by Hsieh et al. [97] showed that the main flavonoids detected in fresh tomato peel were quercetin, myricetin, apigenin, catechin, puerarin, fisetin, hesperidin, naringin, rutin and their levels were reported as 4.2, 2.9, 1.9, 0.9, 0.8, 0.5, 0.3, 0.2, and 0.2 mg/100 g, respectively. It has been proven that tomato peel extracts contain high amounts of kaemferol-3-*O*-rutinoside (from 8.5 to 142.5 mg/kg) [127], quercetin derivatives, *p*-coumaric acid and chlorogenic acid derivative [150,151]. The main phenolic acids identified in tomato peel are protocatechuic, vanillic, gallic, catechin and caffeic acid. Their corresponding concentrations were 5.52, 3.85, 3.31, 2.98, and 0.50 mg/100 g, respectively [134]. The results of Lucera et al. [152] showed that tomato peels contain 4.90 mg/g DW of total phenolic and 2.21 mg/g DW of total flavonoids. The total polyphenolic content in tomato peels and seeds was higher than in the pulp. On the other hand, tomato peel has a very small amount of anthocyanin [153].

Tomato seeds are considered a potential natural source of antioxidants due to their rich phytochemical profile. Many publications indicate that tomato seeds contain, e.g., carotenoids, proteins, polyphenols, phytosterols, minerals and vitamin E [154]. According to Eller et al. [155], the total content of phenolic compounds in the tomato seed extract was 20.66 mg/100 g. Quercetin-3-*O*-sophoroside, isorhamnetin-3-*O*-sophoroside, and kaempferol-3-*O*-sophoroside were present in the highest concentrations of the total phenolic compounds. Quercetin derivatives contributed approximately 37% of the total flavonoid content. Pellicanò et al. [156] found naringenin (84.04 mg/kg DW) as the most abundant flavonoid identified, followed by caffeic acid (26.60 mg/kg DW). Apart from phenolics, carotenoids are the next class of bioactive compounds present in tomato seeds. Qualitatively, the carotenoid composition (*β*-carotene and lycopene isoforms: lycopene all *trans*, lycopene *cis* 1, lycopene *cis* 2, lycopene *cis* 3) in tomato seeds is similar to that of the carotenoids in tomato fruit [157].

Tomato waste has attracted great interest due to its biological activity and potential applications of phytochemicals (Table 11).


**Table 11.** Biological activity and potential applications of phytochemicals obtained from tomato wastes.

#### *2.6. Banana Residues*

Banana (*Musa* spp., Musaceae family) is one of the main fruit crops cultivated for its edible fruits in tropical and subtropical regions. The main by-product of bananas is its peels, which represent approx. 30% of the whole fruit [164]. Moreover, banana waste also includes small-sized, damaged, or rotting fruit, leaves, stems, and pseudoparts. Banana peels are sometimes used as feedstock for livestock, goats, monkeys, poultry, rabbits, fish, zebras, and many other species. They are rich in vitamin B6, manganese, vitamin C, fiber, potassium, biotin, and copper [165], but also in phytochemicals with high antioxidant capacity such

as phenolics (flavonols, hydroxycinnamic acids, gallocatechin), anthocyanin (delphinidin, cyanidin), carotenoids (*β*-carotenoids, *α*-carotenoids, and xanthophylls), catecholamines, sterols and triterpenes (Table 12). Banana peels are natural antacids and are helpful in acid reflux, heartburn, and diarrhea [165].

**Table 12.** Phytochemicals identified in banana wastes and their concentration.



a expressed in mg GAE kg−<sup>1</sup> DM, <sup>b</sup> expressed in mg QE kg−<sup>1</sup> DM, <sup>c</sup> depending on the method of extraction,

d expressed in molar proportion (%), <sup>e</sup> expressed in ug/mL of crude extract, <sup>f</sup> expressed in mg kg−<sup>1</sup> of dry extract.

Previous studies reported that the banana peel is rich in chemical compounds as antioxidant and antimicrobial activities [167–169,171]. Moreover, ethanoic extract from banana peel exhibited the strongest antihyperglycemic activity in comparison with the extract from pulp, seed, and flower [172]. Phytochemicals derived from banana peel were tested as a biofungicide against *Fusarium culmorum* and *Rhizoctonia solani* and as a bactericide against *Agrobacterium tumefaciens* for the natural preservation of wood during handling or in service. Encapsulation is successfully investigated as the method for stabilizing the banana peel extract and its bioactive compounds during storage [173].

Other phytochemical components present in the banana peel extracts, such as ethanediol and butanediol, were determined as highly reducing agents to synthesize silver nanoparticles, which are significant to the medical and chemical industries [173].

The harvesting of the fruits in the plantation requires the decapitation of the whole; therefore, the valuable banana by-products, in addition to peels, are the pseudostem, leaves, inflorescence, and fruit stalk, but also rhizome, which can also be used as a raw material for the acquisition of phytochemicals [174]. Kandasamy et al. [170] isolated three compounds from the pseudostem and rhizome of bananas, including chlorogenic acids, cycloeucalenol acetate, and 4-epicyclomusalenone. Crude extract and isolated compounds are characterized by strong antibacterial, antifungal, antiplatelet aggregation, and anticancer activities.

Using the inflorescence of bananas, anthocyanins can be obtained as good biocolorants with attractive colors, moderate stability in food systems, water solubility, and benefits for health [175]. Cyanidin-3-rutinoside, as the main compound, could be exploited as a cheap source of natural food colorant.

The newest application and explored properties of biologically active compounds from banana residues are presented in Table 13.


**Table 13.** Biological activity and potential applications of phytochemicals obtained from banana residues.


#### *2.7. Apple Residues*

Poland is the main producer of apples in the world, with an annual production of over 4 million tons [177]. About 25% of apple biomass was wasted during crop and processing. Apple pomace as a waste from apple juice and cider processing consists mainly of apple skin/flesh, seeds, and stems [178]. Until recently, apple waste was used as livestock feed, bioenergy feedstock, as well as for food supplementation and pectin extraction, but still, it is far from being used at its full potential, particularly considering its application in the pharmaceuticals and cosmetics industry [179,180]. Nonetheless, apple pomace has the potential to become a source of valuable biomaterials for agriculture. It contains numerous phytochemicals in the form of pectin and dietary fibers, but also polyphenols, triterpenoids, and volatiles. Interestingly, apple pomace is a richer source of antioxidants than fresh fruits itself because it has a significantly lower content of water; moreover, many valuable bioactive compounds are found mainly in the peels and seeds [180].

Polyphenols are the main valuable constituents of apple pomace. Waldbauer et al. [181] reported that the total phenolic content in apple pomace is in the range of 262–856 mg of total phenols/100 g. This content differs between studies due to the use of different solvents, extraction conditions, and apple varieties [182,183].

Four major phenolic groups are hydroxycinnamic acids, dihydrochalcone derivatives (phloretin and its glycosides), flavan-3-ols (catechin and procyanidins), and flavonols (quercetin and its glycosides) [184,185].

Although the phytochemical composition of apple pomace has been studied for a long time, new compounds with beneficial properties are still being isolated and identified. Ramirez-Ambrosi et al. [186] identified 52 phenolic compounds using a newly developed, rapid, selective, and sensitive strategy of ultrahigh-performance liquid chromatography with diode array detection coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (UHPLC-DAD–ESI-Q-ToF-MS) with automatic and simultaneous acquisition of exact mass at high and low collision energy. Among new compounds, two dihydrochalcones (two isomers of phloretin-pentosyl-hexosides) and three flavonols (isorhamnetin-3-*O*-rutinoside, isorhamnetin-3-*O*-pentosides and isorhamnetin-3- *O*-arabinofuranoside) have been tentatively identified for the first time in apple pomace.

One of the compounds newly identified in the last few years in apple pomace is monoterpene–pinnatifidanoside D [185]. This compound has been isolated for the first time from *Crataegus pinnatifida* and exhibited small antiplatelet aggregation activity.

Mohammed and Mustafa [187] and Khalil and Mustafa [188] isolated and structurally elucidated novel furanocoumarins from apple seeds. Isolated compounds exhibited promising antimicrobial activity against *Pseudomonas aeruginosa*, *Klebsiella pneumonia*, *Haemophilus influenzae*, *Escherichia coli*, *Candida albicans*, and *Aspergillus niger*.

The main compounds determined in apple by-products with ranges of their concentrations are listed in Table 14.

**Table 14.** Total phenolic content (TPC), total flavonoid content (TFC), and main phytochemicals identified and quantified in apple pomace.




\* dm—dry matter, <sup>a</sup> expressed as mg gallic acid equivalent, <sup>b</sup> expressed as quercetin equivalent, <sup>c</sup> depending on the methods of extraction or apple pressing, <sup>d</sup> depending on apple varieties, <sup>e</sup> expressed as rutin equivalent, f expressed in % of the oil extracted from apple seeds, \*\* determined in seeds, \*\*\* determined in peels.

73

Many have been written about the application of apple pomace itself. However, the present work concerns the properties and application of bioactive compounds derived from apple pomace. The newest studies reported valuable activities and interesting applications of phytochemicals from apple pomace are listed in Table 15. Preclinical studies have found apple pomace extracts and isolated compounds improved lipid metabolism, antioxidant status, and gastrointestinal function and had a positive effect on metabolic disorders (e.g., hyperglycemia, insulin resistance, etc.) [193]. As was reported by Goł˛ebiewska et al. [194], despite medicine and cosmetics, apple pomace phytochemicals found recent applications in building and construction industries as green corrosion inhibitors and wood protectors [194].


**Table 15.** Biological activity and potential applications of phytochemicals obtained from apple residues.

Phenolic content is related to the antioxidant properties of apple pomace, and procyanidins are considered the major contributors to the antioxidant capacity of apples. Despite high concentrations in apples, catechins and procyanidins are very often absent in the extract from apple pomace. The exposure of polyphenols to polyphenoloxidase during apple processing caused, in addition to native apple phytochemicals, their oxidation products also represent a significant part of the overall polyphenolic fraction. Moreover, the polyphenols can interact non-covalently with polysaccharides; thus, they become nonextractable. Fernandes et al. [178] reported that such complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation. Moreover, it has been revealed that the use of appropriate extraction procedures, such as microwave-superheated water extraction (MWE) of the hot water/acetone, as well

as additional hydrolysis, made it possible to recover these valuable compounds from apple pomace. This knowledge will allow for designing more diversified solutions for agro-food waste valuation [178]. The strong antioxidant in apple pomace is quercetin, which has protective effects against breast and colon cancer, as well as heart and liver diseases [203].

Apple is a unique plant in the *Rosaceae* family due to the high content of phloridzin, a major phenolic compound in commercial varieties of apples [203]. Phloridzin has antidiabetic potential and could be applied as a natural sweetening agent [200]. Phloridzin from apple waste was also tested as the substrate for the production of food dye through its enzymatic oxidation. The yellow product, so-called phloridzin oxidation products (POP), turned out to be a good alternative to tartrazine and other potentially toxic food yellow pigments [200,201].

Interesting phytochemicals of apple pomace are triterpenoids, particularly ursolic acid. It has attracted attention because of its therapeutic potential associated with several functional properties such as antibacterial, antiprotozoal, anti-inflammatory, and antitumor [196]. Wo´zniak et al. [190] optimized the method of its extraction using supercritical carbon dioxide. The data obtained allowed the prediction of the extraction curve for the process conducted on a larger scale.

As has been mentioned previously, apple pomace contains some amount of seeds. Walia et al. [192] proved that also apple seed oil could be a promising raw material for the production of natural antioxidants and anticancer agents. The authors tested the fatty acid composition and physicochemical and antioxidant properties of oil extracted from apple seeds separated from industrial pomace. The dominant fatty acids were oleic acid (46.50%) and linoleic acid (43.81%).

The major constituent in apple seed is also amygdalin, which may be metabolized to toxic hydrogen cyanide [203,204]. However, in the literature, there are also several reports of the positive pharmacological activity of amygdalin. Luo et al. [205] showed its antifibrotic properties in the case of liver fibrosis. Song and Xu [206] proved that amygdalin exhibits analgesic effects in mice, probably by inhibiting prostaglandins E2 and nitric oxide synthesis. Despite so many above reports, there is still a need for human and animal studies to confirm the protection against the disease's effects of apple pomace.

#### *2.8. Winery Waste*

The major winery by-products are grape pomace and marc, including seeds, pulp, skins, stems, and leaves. Bioactive phytochemicals present in residues from wine-making are mainly represented by polyphenols belonging to various groups of compounds, such as phenolic acids (hydroxybenzoic acids and hydroxycinnamic acids), flavonoids (flavanols or flavan-3-ols, anthocyanins, proanthocyanidins, flavones, and flavonols), and stilbenes and anthocyanins. The relative concentrations of the different phenolic compounds are influenced by genotype (red or white grapes), a distinct fraction of residues, as well as agro-climatic conditions [207]. The presence of polyphenolic compounds in grape residues supports the potential of the investigation and valorization of this agro-industrial waste. The compounds identified in grapes by-products with their concentrations are listed in Table 16.

**Table 16.** Phytochemicals identified and quantified in grape residues.






a expressed in mg per kg of dry matter (DM), <sup>b</sup> expressed in mg per kg of fresh weight, <sup>c</sup> expressed in mg per kg of the extract, <sup>d</sup> expressed in mg per g of total lipids extracted from grape pomace, <sup>e</sup> depending on methods of extraction, <sup>f</sup> depending on varieties of grapes, <sup>g</sup> depending on the part of the pomace: seeds, skins, stems.

The residues derived from the grape processing contain phytochemicals of interest for the production of preservatives, dyes, enriched foods, medicines, and products aimed at personal care, pharmaceutical, and cosmetic industries. The presence of bioactive compounds with antioxidant, antimicrobial, anti-inflammatory, anti-tumor, and protective activity of the cardiovascular system provides possibilities for many applications [221]. The potential beneficial role of phytochemicals of grape pomace in the prevention of disorders associated with oxidative stress and inflammation, such as endothelial dysfunction, hypertension, hyperglycemia, diabetes, and obesity, is due to the mechanisms concerned especially modulation of antioxidant/prooxidant activity, improvement of nitric oxide bioavailability, reduction of pro-inflammatory cytokines and modulation of antioxidant/inflammatory signal pathways [222].

It has been proven that the antioxidant properties of polyphenols in grape pomace help to prevent radical oxidation of the polyunsaturated fatty acids of low-density lipoproteins (LDL) and hence, are conducive to the prevention of cardiovascular diseases [223]. The compounds derived from grape pomace were also tested for their anti-inflammatory and anti-carcinogenic effect [224]. Álvarez et al. [225] studied the impact of procyanidins from grape pomace as inhibitors of human endothelial NADPH oxidase and stated the decrease in the production of reactive oxygen species. A rich source of procyanidins is grape seeds. They are widely consumed in some countries in the form of powder as a dietary supplement because of several related health benefits associated with procyanidins. They present antitumor-promoting activity, inhibit growth and induce apoptosis in human prostate cancer cells, as well as significantly reducing atherosclerosis in the aorta.

Seeds contain a very broad spectrum of procyanidins, with the dominant compounds being the dimers, trimers, and tetramers of catechin or epicatechin. Higher polymers are also present but at much lower abundance. Besides, every polymer can also be found as a gallic acid ester.

Very important is the anti-microbial activity of bioactive compounds included in grapes wastes. Mendoza et al. [226] demonstrated the antifungal properties of extracts from winery by-products against *Botrytis cinerea*, the causal agent of gray mold, considered the most important pathogen responsible for postharvest decay of fresh fruit and vegetables. Moreover, a few reports are available in the literature about the effective action of polyphenol-rich extracts from vinification by-products against various pathogenic bacteria and insects, e.g., *Listeria monocytogenes*, *Leptinotarsa decemlineata*, and *Spodoptera littoralis* [1]. The potential health benefits of plant phenolics cause much interest and consideration in a lot of agri-food applications for phenolics extracted from grape wastes [16]. There are a lot of studies on the application of phytochemicals from grape pomace in the meat industry [221].

To facilitate the industrial application of wine waste polyphenols, encapsulation was recently developed to improve the stability of valuable compounds in different conditions of light and temperature [227,228].

The examples of the newest potential applications and valuable properties of phytochemicals derived from winery waste are listed in Table 17.


**Table 17.** Biological activity and potential applications of phytochemicals obtained from grape residues.


#### *2.9. Citrus Residues*

Citrus fruits from the family *Rutaceae* include oranges, lemons, limes, grapefruits, mandarins, and tangerines. They are well known for their nutritional value, as they are good sources of dietary fiber, pectin, vitamin C, vitamin B group, carotenoids, flavonoids, and limonoids (Table 18). It is estimated that approximately 140 chemical components have been isolated and identified from citrus peels, and flavonoids are the main group of phytochemicals with biological activity [245]. Afsharnezhad et al. [165] evaluated the antioxidant potential of extract from various fruit peels and stated that the maximum DPPH radical scavenging activity, total phenols, and total anthocyanins were observed in orange peels.






<sup>a</sup> depending on methods of extraction, <sup>b</sup> expressed in mg kg−<sup>1</sup> of fresh matter of peel, <sup>c</sup> expressed in mg kg of the extract.

Citrus peels are widely used by-products for the production of essential oils, which have great commercial importance due to their aroma, antifungal and antimicrobial properties. Citrus essential oil is employed in the food industry, perfumes, cosmetics, domestic household products, and pharmaceuticals [257]. The main ingredient is limonene, accounting for more than 94% of citrus essential oil [258]. It is used as an insect-killing agent in pesticides and a good biodegradable and non-toxic solvent [257]. Furthermore, limonene has shown regulatory effects on neurotransmitters and stimulant-induced changes in dopamine neurotransmission [258].

The citrus waste contained high amounts of organic and phenolic acids, as well as flavonoids. Among flavonoids, the main compounds are flavanones and flavones (such as naringenin, hesperetin, and apigenin glycosides) as well as polymethoxylated flavones (PMFs), not found in other fruit species [259,260]. Okino Delgado and Feuri [258] indicated that polymethoxylated flavones, at a dosage of 250 mg/kg, exhibit an anti-inflammatory effect comparable to ibuprofen. The most widely studied PMFs are tangeretin and nobiletin. They are exclusively derived from citrus peels. Lv et al. [261] stated that nobiletin and its derivatives showed anti-cancer activity. Generally, anticancer activity increases with the increasing number of methoxy groups because PMFs have then higher hydrophobicity for approaching and penetrating cancer cells [244]. Moreover, PMFs exhibit a broad spectrum of other biological activities such as anti-obesity, anti-atherosclerosis, antiviral and antioxidant properties [262,263].

Among flavanones, citrus peel is rich in eriocitrin, hesperidin, diosmin, neohesperidin, didymin, and naringin. Chiechio et al. [264] used red orange and lemon extract rich in flavanones for in vivo assays on male CD1 mice fed with a high-fat diet. The results showed that an 8-week treatment with the extract was able to induce a significant reduction in glucose, cholesterol, and triglyceride levels in the blood, with positive effects on the regulation of hyperglycemia and lipid metabolism. Barbosa et al. [265] tested flavanones obtained from citrus pomace by enzyme-assisted and conventional hydroalcoholic extraction as an agent against *Salmonella enterica* subsp. *enterica*. Tested extracts decreased the expression of genes associated with cell invasion. Moreover, the results suggest that extracts and flavanones inhibit *Salmonella Typhimurium* adhesion by interacting with fimbriae and flagella structures and downregulating fimbrial and virulence genes.

Citrus peels also contained some flavonols, such as rutin, isorhamnetin 3-*O*-rutinoside, quercetin-*O*-glucoside, and myricetin, as well as phenolic acids, but at a much lower concentration. It has been proven that *Citrus reticulata* waste extract, mainly including rutin, was the most effective against gram-negative bacteria and the three pathogenesis fungi: *Bacillus subtilis*, *Candida albicans* and *Aspergillus flavus* [266].

Citrus seeds are also a good source of valuable components, particularly oil rich in carotenoids (19.01 mg/kg), phenolic compounds (4.43 g/kg), tocopherols (135.65 mg/kg) and phytosterols (1304.2 mg/kg) [251]. This oil was characterized by high antioxidant activity ranging from 56.0% to 70.2%.

A summary of the main phytochemical constituents, together with their concentrations in citrus residues, as well as their newest applications and properties, is presented in Tables 18 and 19, respectively.


**Table 19.** Biological activity and potential applications of phytochemicals obtained from citrus residues.


#### *2.10. Olive Waste*

The cultivation of olive trees is a widespread practice in the Mediterranean region, accounting for about 98% of the world's olive cultivation. A large number of phenolic compounds occur in both olive oil and olive waste that includes both leaves and the residues of oil production [275,276]. Their chemical characterization was reported by Dermeche et al. [277]. The main groups of phenolic compounds in olive mill wastes are phenolic acids, secoiridoids, and flavonoids, and the most abundant polyphenols are oleuropein, hydroxytyrosol, verbascoside, apigenin-7-glucoside, and luteolin-7-glucoside [278] (Table 20). Olive mill wastewater obtained during oil production is a complex mixture of vegetation waters and processing waste of the olive fruit; it is characterized by a dark color, strong odor, a mildly acidic pH, and a very high inorganic and organic load [279]. The organic fraction consists essentially of sugars, tannins, polyphenols, polyalcohols, proteins, organic acids, pectins and lipids [277]. About 30 million m<sup>3</sup> of olive mill wastewater are produced annually in the world as a by-product of the olive oil extraction process; because of the high polyphenolic content (0.5–24 g/L), this by-product is difficult to biodegrade and a relevant environmental and economic issue [280].

**Table 20.** Phytochemicals identified and quantified in olive waste.



#### **Table 20.** *Cont.*

\* OMWW—olive mill wastewater, \*\* olive mill solid waste, <sup>a</sup> percentage of total phenolic content based on peak areas, <sup>b</sup> expressed in mg/g dry weight, <sup>c</sup> depending on the methods of extraction.

Polyphenols also occur in the leaves [287]. These compounds confer bioactive properties on olive leaf extracts, such as antioxidant, antimicrobial, and antitumor activity; the capacity to reduce the risk of coronary heart disease was also reported [288]. Olive leaves can be collected as a by-product during oil processing (about 10% of the total weight of the olives) but can also be a residue of olive tree pruning. Some authors estimated that about 25 kg of by-products (twigs and leaves) could be obtained annually by pruning per tree [289]. To date, this by-product is often used as animal feed, even if this natural resource rich in antioxidant phenolic compounds should be valorized [290].

The qualitative and quantitative content of phenolic compounds is often heterogeneous in olive by-products; however, several studies reported the bioactive properties of these phenolic compounds, promising potential as antioxidant, anti-inflammatory, and antimicrobial agents. The antioxidant activities of olive mill wastewater and olive pomace have been demonstrated by different antioxidant assays as DPPH radical-scavenging activity, superoxide anion scavenging, LDL oxidation, and the protection of catalase against hypochlorous acid [281,291,292]. An overview of the pharmacology of olive oil and its active ingredients has been reported by Visioli et al. [293]. Recently, a novel stable ophthalmic hydrogel containing a polyphenolic fraction obtained from olive mill wastewater was formulated [294]. Among olive polyphenols, hydroxytyrosol is one of the main phenolic compounds; it can occur in its free form or as secoiridoids (oleuropein and its aglycone). For its polarity, it is more abundant in olive mill wastewater and pomace rather than in olive oil. Anticancer, antioxidant, and anti-inflammatory properties have been reported for hydroxytyrosol [295,296]. In vitro antioxidant and skin regenerative properties have been reported by Benincasa et al. [297].

Moreover, the polyphenol fraction obtained from olive mill wastewater showed activities against bacteria, fungi, plants, animals, and human cells; antibacterial activities against several bacterial species (*Staphylococcus aureus*, *Bacillus subtilis*, *Escherichia coli* and *Pseudomonas aeruginosa*) have been reported by Obied et al. [298]. Fungicidal activities have also been reported [299]. Moreover, the effects of phenolic compounds from olive waste on *Aspergillus flavus* growth and aflatoxin B<sup>1</sup> production were investigated [300,301]. The olive mill wastewater polyphenols did not inhibit the *Aspergillus flavus* fungal growth rate but significantly reduced the aflatoxin B<sup>1</sup> production (ranging from 88 to 100%) at 15% concentration [302].

Finally, cytoprotection of brain cells by olive mill wastewater has been studied by Schaffer et al. [303]. The cytoprotective effects were correlated to the content of hydroxytyrosol.

These studies showed the numerous beneficial and bioactive activities of polyphenols fraction obtained by olive by-products; for their use, it is often carried out an appropriate fractionation and/or purification to control their concentration and to avoid some antagonist effects.

Various valuable properties and the newest studies on the application of biologically active compounds derived form olive waste are presented in Table 21.


**Table 21.** Biological activity and potential applications of phytochemicals obtained from olive waste.


\* OMWW—olive mill wastewater.

#### **3. Conclusions**

The ever-increasing amount of processed food raw materials entails an increasing amount of biowaste. Their management has become a growing problem. The consulted literature shows that discussed waste still contains valuable ingredients, medicinally important phytochemicals, and good antioxidants, so it is very important to valorize them. Currently, the recovery of different valuable phytochemicals from agro-industrial waste has become an imperative research area among the scientific community because agro-industrial residues of plant materials are a cheap and natural source of bioactive compounds, which can be used in the prevention and treatment of various diseases. Despite many studies on the valuable properties and potential applications, still, not many solutions are implemented in the industry. This is probably caused by legislation that can affect the valorization of such waste biomass. There are not many regulatory and legal provisions for their use. In the European Union, the use of agricultural residues as food ingredients is regulated by the European Community Regulation (EC) No 178/2002. However, in order to use them as natural additives, proper authorization as a novel food is necessary (Regulation (EC) No 2015/2283) [304]. There is no doubt that the industrial application of the extracts needs to be regulated.

According to the circular bioeconomy and biorefinery concept, food waste should be recycled inside the whole food value chain from field to fork in order to formulate functional foods and nutraceuticals. Nonetheless, it is important to implement environmentally friendly industrial extraction procedures. Moreover, despite so many above reports, there is still a need for human and animal studies, as well as studies in the field in the case of plants, to confirm the protective effect of such phytochemicals against diseases.

Taking into account the European Union's emphasis on the development of a circular economy and reducing the carbon footprint, it is expected that the effective application of these wastes will be carried out and that regulations will be developed in accordance with needs.

**Author Contributions:** Conceptualization, M.O., I.K. and W.O.; resources, W.O., I.K.; Visualisation, M.O., I.K. and T.B.; writing—original draft preparation, M.O., I.K. and T.B.; writing—review and editing, M.O. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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