The Sorbus spp.—Underutilised Plants for Foods and Nutraceuticals: Review on Polyphenolic Phytochemicals and Antioxidant Potential

The Sorbus spp. are valuable plants, which have been used for ornamental purposes, in traditional medicines and less seldom in foods. Recent studies have revealed different anatomical parts of the Sorbus spp. to contain valuable phytochemicals demonstrating various bioactivities. However, in terms of applications in the products intended for human consumption, Sorbus still remains as an underutilised genus. The increasing number of studies on phytochemicals, antioxidant potential and other bioactivities of Sorbus extracts has revealed the prospects of expanding its use in natural medicines, cosmetics and as innovative food ingredients, which might find wider applications in functional foods and/or nutraceuticals. Caffeoylquinic acids, flavonoids and proanthocyanidins have been reported in various Sorbus spp. as the most abundant polyphenolic antioxidants. The preparations of various plant anatomical parts have been used in ethnopharmacology as natural remedy for treating bacterial, viral, inflammatory diseases including tumors. Sorbus spp. plant parts have also been tested for management of diabetes, neurological, and cardiovascular disorders. The present review is focused on Sorbus plants (in total 27 Sorbus spp.), their composition and properties in terms of developing promising ingredients for foods, nutraceutical, cosmeceutical and other applications. It is expected that this review will assist in designing further studies of rowans and other Sorbus spp. in order to expand their uses for various human applications.


Introduction
During the past few decades, search and development for novel highly valued bioactive compounds from plants has become a topical issue for researchers, health professionals, producers, and consumers. Considering vast number of species in the Plant Kingdom, there are still infinite number of under explored plants, which may serve as an excellent platform for discovery of new compounds and developing valuable preparations. Underutilised plants have become of a particular interest in the era of functional foods, nutraceuticals and personalized nutrition. Thus, natural bioactive compounds can play the most important role in the development of health promoting products based on individual genome and/or microbiome [1,2].
Fruits and vegetables have been considered as healthy foods, mainly owed to the presence of high amounts of valuable nutrients such as vitamins, minerals, polyphenolic antioxidants, dietary fibre and others. In this regard, many well-known comprehensively valorised and globally commercialized The subgenus Sorbus, commonly noted as a mountain ash (Amur or European mountain ash), rowan or quick beam, is distributed in the Northern Hemisphere. It has hairless or thinly hairy leaves [3]. This review covers 19 species from the large Sorbus subgenus (Table 1) wilfordii Koehne. Different anatomical parts of these species have been used for medicinal and food purposes ( Figure 1). The leaves of S. tianschanica have been used to treat asthma, ventricular myocytes, dyspnoea, tuberculosis and gastritis [10], while both the leaves and the bark of S. decora are known as an antidiabetic medicine [11]. The bark of S. americana, due to hypo-glycaemic properties has also been used for treating diabetes; while other applications include vaso-relaxant, antitussive and tonic activities [12]. In oriental medicine, the stems and bark of S. commixta have been used to treat arthritis and inflammatory diseases and as hypoglycaemic, vasorelaxant, antitussive and tonic agents [13,14]. The bark preparation of S. cashmiriana has been used to treat nausea and heart diseases, while its berries have been used to cure scurvy [15]. The fruits, stems and bark S. pohuashanensis have been widely used in traditional Chinese medicine for treating chronic tracheitis, tuberculosis and oedema [16]. The fruits of S. sambucifolia have been used in drinks and foods (beverages, jams, jellies, floured dried fruit, etc.), while for medicinal purposes-in case of avitaminosis, arteriosclerosis and as antipyretic or diuretic agent. Indigenous people used to eat fresh S. scopulina berries; however, currently they are sometimes used in pies, preserves, or wine-making The subgenus Sorbus, commonly noted as a mountain ash (Amur or European mountain ash), rowan or quick beam, is distributed in the Northern Hemisphere. It has hairless or thinly hairy leaves [3]. This review covers 19 species from the large Sorbus subgenus (Table 1) Figure 1). The leaves of S. tianschanica have been used to treat asthma, ventricular myocytes, dyspnoea, tuberculosis and gastritis [10], while both the leaves and the bark of S. decora are known as an antidiabetic medicine [11]. The bark of S. americana, due to hypo-glycaemic properties has also been used for treating diabetes; while other applications include vaso-relaxant, antitussive and tonic activities [12]. In oriental medicine, the stems and bark of S. commixta have been used to treat arthritis and inflammatory diseases and as hypoglycaemic, vasorelaxant, antitussive and tonic agents [13,14]. The bark preparation of S. cashmiriana has been used to treat nausea and heart diseases, while its berries have been used to cure scurvy [15]. The fruits, stems and bark S. pohuashanensis have been widely used in traditional Chinese medicine for treating chronic tracheitis, tuberculosis and oedema [16]. The fruits of S. sambucifolia have been used in drinks and foods (beverages, jams, jellies, floured dried fruit, etc.), while for medicinal purposes-in case of avitaminosis, arteriosclerosis and as antipyretic or diuretic agent. Indigenous people used to eat fresh S. scopulina berries; however, currently they are sometimes used in pies, preserves, or wine-making [17]. In folk medicine, the fruits and the inflorescences of S. aucuparia (European rowan) have been used as traditional anti-inflammatory, antidiarrheal, vasodilatory and an appetite-improving agents, as well as a good source of vitamins, diuretic and mild laxative medicine [18,19]. In traditional Austrian medicine, the tea, syrup, jelly or alcoholic tincture of S. aucuparia fruits have been used to treat fever, infections, colds, flu, rheumatism and gout [20].
From the subgenus Aria with 39 species, commonly known as whitebeams, 6 species, namely S. aria Crantz, S. intermedia (Ehrh.) Pers., S. norvegica Hedl., S. folgneri (Schneid.) Rehd., S latifolia (Lam.) Pers, and S. minima (Ley) Hedl. are covered in this review. These species have simple white-hairy leaves and are distributed in the temperate regions of Europe and in Asia. Traditionally, the leaves of S. aria were consumed as antidiarrheal ingredients, while their berries have been used in jellies, jams, brandy, liqueurs, conserves and vinegar, as traditional bread flour extender, diuretic, anti-inflammatory, anti-diarrhoeal, vasodilatory agent and vitamin source [21]. Moreover, the fruits and inflorescences of S. aria have been used as a diuretic, laxative and emmenagogue folk medicine for treating painful menstruation, constipation and kidney disorders [22]. The berries of S. intermedia have been added to bread in Estonia [23], while the berries of S. norvegica, S. folgneri, S latifolia and S. minima were tested for their α-amylase and α-glucosidase inhibitory activities [24].
The subgenus Micromeles, commonly known as Korean whitebeam, alder-leafed whitebeam, contains around 25 narrow leaved species of shrubs and trees with white flowers, distributed from Nepal to the South Kuriles, extending to the Malay Peninsula and Sumatra [25]. In the Korean folk medicine the twigs of the most widely distributed species, S. alnifolia (Siebold & Zucc.) K. Koch., were used for treating neurological disorders [26].
Aria, Micromeles and Chamaemespilus have simple leaves and pomes with groups of tanniferous cells, however, Chamaemespilus (false medlar or dwarf whitebeam) differs by a rather different flower shape [27]. Chamaemespilus is not reviewed in the current study due to the lack of information about its uses and antioxidant activity.
The subgenus Torminaria (common names wild service tree, chequers, and checker tree) with three species is distributed in the temperate Europe, south to the mountains of North Africa and east to the Caucasus ranges. It has maple-like simple, 3-5-lobed leaves and brown pomes without groups of tanniferous cells. The fruits of S. torminalis have been traditionally used as diuretic or anti-inflammatory, antidiarrheal (dried), vasodilatory remedy and as a source of vitamins [27,28]. In the current work, the uses and antioxidant potential of 2 varieties of S. torminalis, (var. torminalis and semitorminalis) are surveyed.
The subgenus Cormus with pomes without starch and groups of tanniferous cells [27] and compound leaves, is distributed in the warm-temperate Europe, North Africa and Asia. Unlike the subgenus Sorbus, Aria and Torminaria, whose fruit carpels are not fused, subgenus Cormus is with distinct fused carpels in the fruit. In this review only S. domestica, also known as true service tree or sorb tree [29], is included. It has been reported that the fruits of S. domestica are traditional anti-inflammatory, antidiarrheal (dried), antidiabetic, diuretic, vasodilatory agents and vitamin source [30].

Nutritional Composition
Wild rowanberries are not consumed as fresh fruits due to their specific astringent taste, imparted mainly by the tannins. These cause the dry feeling in the mouth when consumed. Therefore, they have rather limited applications for producing food products. However, due to the nutritive value and health benefits the berries of S. aria, S. aucuparia, S. domestica, S. sambucifolia, S. scopulina, and S. torminalis have been traditionally used for pressing juice, in alcoholic beverages, purees, jams and jellies [28,35]. These benefits are due to the significant amounts of phytochemicals, such as vitamins, carotenoids, and phenolic acids as well as important in nutrition minerals, iron, potassium, and magnesium. In addition, rowanberries contain a sweet-tasting sugar alcohol sorbitol, which slowly metabolizes in the human body and therefore is suitable as a sweetener for people suffering from diabetes [45].
It was reported that rowanberries contain 3-fold higher amount of ascorbic acid than oranges [5]. For instance, Mrkonjić et al. [28] determined approximately 0.1 mg/g d.w. (dry weight) of ascorbic acid in S. aucuparia berries and 0.42 mg/g dw in fruit jam. The recommended dietary allowance of ascorbic acid is 60 mg per day, while 5-7 mg a day prevents scurvy. Tocopherols are important fat-soluble vitamins in rowanberries. The mean concentrations of vitamin E activity demonstrating α-tocopherol, δ-tocopherol, and γ-tocopherol in S. aria and S. aucuparia were reported 2.82, 0.11, 2.01 µg/g dw and 4.89, 0.58, 1.71 µg/g dw, respectively [46]. Klavins et al. [47] determined even higher content of α-tocopherol (3.34 µg/g dw) in S. aucuparia fruit, while the content of γ-tocopherol was remarkably lower, 0.25 µg/g dw. The recommended intake of vitamin E for adults is in the range of 7 to 15 mg per day. The epidemiological studies showed that humans who consumed vitamin E richer foods had lower incidence of cancer, dementia and/or cardiovascular diseases [48].
In nature, β-carotene, a precursor (inactive form) of vitamin A, is a strongly coloured red-orange pigment, which is abundant in some plants and fruits. Bern , a and Kampuse reported that S. aucuparia contains 2.5 mg of total carotenoids per 100 g [49]. The average daily intake of the strong antioxidant β-carotene is in the range of 2-7 mg, as estimated from a pooled analysis of 500,000 women living in the US, Canada, and some European countries [50] The minerals are important for all living organisms. Aslantas et al. reported high content of 8 essential minerals in S. aucuparia (in mg/100 g): potassium, 154; phosphorus, 12.3; calcium, 29.9; magnesium, 27.84; iron, 2.42; copper, 0.294; zinc, 0.861; and manganese 0.503 [51]. The tree bark of S. domestica has been reported as a good source of Ca, Zn, Fe, while the seeds were rich in K, Mg, Fe and Zn [30]. Plant oils are important as food ingredients and as a source of essential fatty acids for human nutrition. In seed oils of S. aucuparia the sum of linoleic and oleic acids exceeded 90% of the total fatty acids [37]. Ivakhnov et al. [52] optimized the procedure for oil extraction from S. aucuparia alcoholic beverage production waste using the supercritical CO 2 as a solvent and recovered 9.02% (w/w) high quality oil.

Total Phenolic Content
In general, the leaves and inflorescences of Sorbus spp. were reported to contain higher amounts of the total phenolic content (TPC) than the fruits ( Table 2). Usually TPC is expressed in gallic acid equivalents (GAE). Thus, the highest TPC was reported in the dried leaves of S. wilfordii (12.31% GAE), as well as in the inflorescences of S. aucuparia (11.83% GAE) [53]. Predominantly, in the tested plant parts of the Sorbus spp., the total level of phenolics was significantly higher in the inflorescences than in the leaves [54], except for S. gracilis, when the TPC in the leaves was slightly higher than in the inflorescences, 11.06 and 10.72% GAE, respectively [53]. The highest TPC in fruit was detected in S. aria (2.98% GAE) dw; the fruits of S. aucuparia and S. intermedia contained only slightly lower TPC, 2.68% and 2.24% GAE dw, respectively [54]. The lowest TPC values among the tested Sorbus spp. was found in the S. americana fruits; it was only 3.60-5.39 mg/g dw [54,55]. Gaivelyte et al. analysed leaf and fruit material of 10 Sorbus spp. and 9 cultivars and found that the TPC varied approximately 5 times, both in leaf and fruit samples, i.e., in the range of 7.18-35.74 mg/g and 2.24-11.19 mg/g, respectively [56]. The berries of S. aria and S. aucuparia grown at different altitudes were compared; however, there was no correlation between TPC, total proanthocyanidins, radical scavenging capacity and growing site. Nevertheless, slightly higher TPC values were observed in S. aucuparia, while S. aria had higher content of proanthocyanidins [57].
TPC may highly depend on berry maturity, while the recovery of phenolics depends on extraction solvent. For instance, the diethyl ether fraction separated from the crude methanol extract isolated from fruit pulp of S. domestica berries matured at room temperature for 1 week had the highest TPC [58]. Bobinaitė et al. [59] reported the TPC in acetone, ethanol and water extracts of rowanberry pomace, which was almost similar, 10.94, 10.43 and 9.60 mg/g, respectively; while the content of individual compounds depended remarkably on the applied solvent. It was suggested that considering only slight differences in the recovery of total phenolics between the applied solvents, water would be the most attractive due to the price, availability and safety.
Olszewska et al. [37] investigated the effects of extraction with chloroform and 70% methanol and fractionation with diethyl ether, ethyl acetate, n-butanol of soluble in different solvents substances present in inflorescences and leaves of 7 Sorbus spp., namely S. aucuparia, S. commixta, S. decora, S. gracilis, S. koehneana, S. pogonopetala and S. wilfordii. N-butanol and ethyl acetate were the most effective in recovering antioxidants from Sorbus leaves, whereas ethyl acetate, n-butanol and diethyl ether fractions of S. pogonopetala and S. wilfordii leaves contained the highest TPC, 39.56-58.17% dwe (dry weight of extract).

Phenolic Acids
Chlorogenic (3-O-caffeoylquinic acid, 3-CQA) and neochlorogenic acids (5-O-caffeoylquinic acid, 5-CQA) are the main phenolic acids reported in Sorbus spp. [53,55,57]. Moreover, it has been reported that caffeoylquinic acids constitute 56-80% of the total phenolics in Sorbus fruits, whereas the cultivated berries contain less caffeoylquinic acids than wild rowanberries [60]. The content of chlorogenic acid in the berries of S. aucuparia was up to 10.01 mg/g dw [57], while the content of neochlorogenic acid in the tested 5 cultivars was up to 7.31 mg/g dw [60]. Generally, the content of caffeoylquinic acids in the inflorescences was reported to be higher than in the leaves or berries. The predominant caffeoylquinic acid in the all assayed inflorescence samples was chlorogenic acid [54][55][56][57]60] with the highest concentration in S. sambucifolia, 4.17% dw [53] the highest contents of neochlorogenic acid were in the inflorescences of S. koehneana (1.98%), S. decora (1.26%) [53], and S. aucuparia (1.37%) [54]. The concentrations of chlorogenic acid in water and methanol extracts, as well as in the jam of S. aucuparia were 5.69, 5.80 and 2.60 mg/g dw, respectively [28]. It seems that some species instead of chlorogenic acids biosynthesize ferulic acid as the major one; in the methanol and water extracts and jams of S. torminalis its content was up to 62.6 µg/g dw [28].
In addition, ferulic acid content was reported in the leaves of some Sorbus spp., such as S. aucuparia, S. aria [43] and S. subfusca [61]. The methanol and water extracts and jams of both S. torminalis var. torminalis and semitorminalis also contained up to 23.2 µg/g dw protocatechuic acid, while in the jam of S. aucuparia its concentration was 12.5 µg/g dw. Protocatechuic acid was also reported in the fruits, leaves and bark of S. alnifolia [62], in the extracts of S. aucuparia, S. commixta, S. gracilis, S. decora and S. koehneana inflorescences [37], in the extracts of S. gracilis, S. pogonopetala, S. wilfordii [37], S. domestica leaves [63] and in the S. domestica fruit pulp [41]. Gallic acid was found only in the water extract of S. torminalis var. semitorminalis in concentration of 5.69 µg/g dw [28].
Sexangularetin was one of the most abundant flavonoid component in the inflorescences; S. aucuparia and S. scalaris contained 0.19% and 0.14% dw, respectively [53]. Epicatechin was reported in the leaves of many Sorbus spp. [71,72], as well as in the berries of S. aucuparia [60] and S. torminalis var. semitorminalis [28]. Hesperidin was found only in the leaves of S. tianschanica [67,73]. The highest levels of proanthocyanidins among the inflorescences of 12 tested species were found in the S. pohuashanensis and S. sitchensis, 7.67% and 7.14% CyE, respectively. Among the 17 leaf samples, S. gracilis had the highest concentration of proanthocyanidins, 6.56% CyE [53]. Among the rowanberries, the highest content of proanthocyanidins was found in the fruits of S. aria, 1.80% CyE [54]. Catechin and epicatechin were the main flavonoid components in the samples of S. decora stembark [74], rootsock [75], but also in the water extract of S. torminalis var. semitorminalis [28].
Quercetin content in methanol extract of S. torminalis var. semitorminalis was 11.0 µg/g while in water extract it was 2-fold lower, 6.53 µg/g [28]. The content of rutin in water and methanol extracts of S. aucuparia was found similar, 82.3 and 80.4 µg/g dw, respectively [28]. Hydroethanolic (70%) extract of dried S. commixta stems and cortex contained higher by 50.43% total polyphenol and flavonoid content than water extract; the former also demonstrated stronger antioxidant capacity [68].
Exceptionally high content of amentoflavone was found in S. torminalis var. semitorminalis water and methanol extracts as well as in its jam, namely 362, 974, and 195 µg/g dw, respectively. However, its content in the extracts and jam of S. torminalis var. torminalis and S. aucuparia differed just slightly: it was 15.8, 19.3 and 16.8 µg/g dw and 10.7, 11.9 and 8.4 µg/g dw, respectively [28]. Up to 119 µg/g dw of quercetin-3-O-glucoside were reported in S. americana [55]. Typically, anthocyanins have been detected in the S. aucuparia cultivars however only in low concentrations, usually less than 1% of the total phenolics in the wild fruits [60]. Bobinaitė et al. [59] reported that the total content of proanthocyanidins in S. aucuparia pomace water extract was 10.4 and 3.8 times, higher than that in the acetone and ethanol extracts, respectively.

Antioxidant Potential of Sorbus spp.
Plant material, suitable for cost-effective production of natural antioxidants should contain reasonable amount of polyphenolics (usually not less than 8-10% GAE/dw), demonstrate comparatively strong antioxidant properties in several assay systems and exhibit as low as possible toxicity, which should be acceptable for human applications [53].
Large number of phytochemicals belonging to various classes of organic compounds have been identified in various Sorbus spp. [4]. The presence of significant amounts of polyphenolic antioxidants, mainly flavonoids and phenolic acids, has also been reported in Sorbus spp. (Table 2). Moreover, many authors observed good positive correlation between the concentration of phenolics, e.g., the sum of proanthocyanidins, caffeoylquinic acids and flavonoid aglycones and antioxidant properties [31,57,58]. Therefore, in many studies rowanberries exhibited significant antioxidant activity (Table 3), which was comparable or in some cases even higher than that of many other edible berries, such as chokeberries and bilberries [76]. Various methods have been applied for assessing antioxidant properties of rowanberries and their extracts, most frequently using the in vitro radical scavenging capacity assays and inhibition of lipid peroxidation [77], reducing power, chain-breaking potential of radical reactions [60] and others. The majority of studies investigated Sorbus fruits, leaves and inflorescences; however, antioxidant properties of tree bark and seed oil were also reported [46].
In order to identify the ability of different solvents to recover antioxidants from S. aria leaves various extracts were tested by DPPH • scavenging method. Among the tested isolates, the EC 50 value of ethyl acetate extract (2.99 mg/L), which contained 11.8% isoquercitrin, 6.0% astragalin, and 3.81% chlorogenic acid, was almost similar to reference antioxidant isoquercitrin, EC 50 2.76 mg/L [65]. Five strongly active constituents, namely isoquercitrin, rutin, quercetin 3-glucoside-7-rhamnoside, chlorogenic and neochlorogenic acids were found to be major components and principally responsible for the radical scavenging capacity of S. aria extracts [65]. Two interesting new coumarins, cashmins A (1) and B (2) were isolated from the methanolic extract of S. cashmiriana. Both compounds demonstrated outstanding antioxidant activity in H 2 O 2 (IC 50 15.4 and 18.6 µmol/mL), as well as in ABTS •+ scavenging assays (IC 50 24.4 and 18.3 µmo/mL). For comparison, IC 50 of ascorbic acid were 11.4 µmol/mL in H 2 O 2 and 6.5 µmol/mL in ABTS •+ assays [15].
Bae et al. [69] tested the effects of treatment with carbohydrate hydrolases on the composition of TPC and flavonoids, as well as antioxidative activity of ethanol extract of dried S. commixta cortex. Amyloglucosidase, α-amylase, α-glucosidase and β-glucanase increased the contents of extractable polyphenols and flavonoids, as well as the DPPH • scavenging capacity; particularly in case of applying β-glucanase [69].
Ethanol recovered antioxidants from S. commixta stems more effectively than hot water with the values of 504.39 and 364.64 µg/mg, respectively. Similarly, ethanol extracts demonstrated slightly higher antioxidant activities than water extracts in Fe 2+ chelating, DPPH • , ABTS •+ , hydroxyl and nitrite radical scavenging assays [68]. Extraction and fractionation of S. domestica fruits harvested at five different maturity stages gave the products with scavenging capacity in the range of 0.341-39.5 mg dwe/mg DPPH • and the following order: water << dichloromethane < ethyl ether < ethyl acetate [58]. The fractions recovered with organic solvents possessed greater radical scavenging capacity than trolox, while the unripe fruits provided more antioxidants than the well-matured berries at room temperature. Finally, radical scavenging values strongly correlated with the total phenolic content in the fractions of S. domestica [58]. Olszewska et al. demonstrated that strong antioxidant fractions might be obtained from 70% methanol extracts of inflorescences and/or leaves of seven Sorbus spp. by using different solvents in a separatory funnel. n-Butanol and ethyl acetate gave the fractions with outstanding antioxidant capacity in the all applied assays: EC 50

Toxic Constituents of Rowanberries
Parasorbic acid, an important inhibitor of germination, has been reported in the fruits and seeds of S. aucuparia at the level of 4-7 mg/g and 0.08-0.12 mg/g fw, respectively [79]. This compound irritates the gastric mucosa and, if consumed at larger amounts, can cause indigestion and kidney damage to humans. However, heat treatment or freezing modifies the parasorbic acid into nontoxic sorbic acid. Parasorbic acid is sensitive to changes of temperature and brakes into safe compounds if the berries are picked after the first frost [34]. The parasorbic acid is almost absent in the cultivated hybrids. The other toxic component in rowanberries is the cyanogenic glycoside prunasin, which is derived from the amino acid phenylalanine; 1 g of the prunasin can liberate 91.5 mg HCN (hydrogen cyanide). Thus, HCN from the seeds of rowanberries, when formed at the levels exceeding 2-3 mg/L, can cause respiratory failure and even death [80]. Therefore, while processing the rowanberry pomace, the separation of the seeds would be essential.

Promising Health Benefits and Related Applications in Foods, Nutraceuticals and Pharmaceuticals
It is evident that among phytochemicals and other nutrients, polyphenolic compounds and ascorbic acid may be considered as the most valuable health beneficial constituents, which have been reported in various anatomical parts of Sorbus spp. The polyphenolics, which may influence the colour and flavour, have demonstrated antioxidant [54,81], antidiabetic [11,82] anti-hyperlipidemic [83], anti-inflammatory [84], antimicrobial [85], anticancer [86,87] antiviral [67], antifungal [79], antitumoral [88], anti-periodontal [89], and anti-osteoarthritis [90] effects, as well as vasoprotective [84], neuroprotective [26,91,92], cardioprotective [36], hepatoprotective [7], properties and COX-2 (cyclooxygenase-2) inhibitory [93] activities. Many of these activities are correlated to antioxidant capacity of bioactive compounds, which at cellular level may neutralize excessive reactive oxygen species, and thereby protect important biomolecules in the conditions of oxidative stress, which can cause cellular injury and development of chronic diseases. Therefore, it has been hypothesized that antioxidant-rich diets might play an important role in neutralising the excessive reactive oxygen species [11]. This hypothesis and increasing amount of evidence in favour of it have encouraged many researchers to test many novel plant-based phytochemicals as natural candidates for developing health beneficial exogenous antioxidants. The other important role of antioxidants is to protect foods and other sensitive to oxidation products during processing and storage in order to extend their shelf life and improve the quality and safety [94]. Compared to pure synthetic compounds natural preparations of phenolic antioxidants can be more effective due to the synergistic effects of various molecules present in the plant-based products. In addition, natural ingredients are usually safer than their synthetic counterparts and therefore are preferred by the consumers [11].
The application of plant-based polyphenolic substances in lipid-containing foods, cosmetics, and medicinal products is hampered by their high polarity (hydrophilicity), which makes them poorly soluble in the lipid medium, which is composed mainly of triacylglycerols. Therefore, for increasing product lipophilicity some studies [94][95][96] applied derivatisation of phenolic compounds by attaching medium or long chain alkyl molecules. For instance, the lipophilised phenolic extract of S. aucuparia was more effective inhibitor of rapeseed oil oxidation during 7-day storage than the untreated one: it reduced peroxide value by 43% and improved the solubility of the phenolics during frying [95]. Hydrophilic fraction of rowanberry pomace contained most of the polyphenolic antioxidants, while lipophilic seed extracts could be beneficial as nutraceutical and cosmetic agents due to the high content of polyunsaturated fatty acids and carotenoids [97].
Water extracts of berries containing high amounts of low molecular weight proanthocyanidins, which were tested as the inhibitors of colon cancer-induced angiogenesis, turned out to be superior in reducing Caco-2 cell viability [59]. Due to the significant content of bioactive phenolics in fruits, the wild rowanberries inhibited lipid oxidation both in liposomes and in emulsions [31]. Aqueous methanol extracts of S. aucuparia fruits were potent antioxidants while the extracts of both S. torminalis varieties, namely torminalis and semitorminalis effectively inhibited the growth of E. coli, var. torminalis being the best inhibitor of Staphylococcus aureus [28]. Polyphenols from two hybrid cultivars of S. aucuparia, Zoltaja and Granatnaja also delayed pathogenic E. coli growth. The phenolic extracts of wild rowanberries and cultivated breed Burka had an inhibitory effect on hemagglutination of E. coli HB101 (pRR7), which expresses the M hemagglutinin [60]. S. aucuparia berry extract isolated with acidified acetone also demonstrated high activity against Salmonella enterica ssp. enterica ATCC BAA-2162, and Pseudomonas aeruginosa ATCC 9027; it also exhibited moderate activity towards the two Listeria monocytogenes strains and Proteus vulgaris [66]. Water extract of S. aucuparia fruit inhibited the growth of Gram-positive E. faecalis, S. aureus and Gram-negative S. enterica, as well as the viability of C. freundii and B. cereus [59]. These findings prove that S. aucuparia extracts express strong antimicrobial activity against a wide scale of microorganisms and possess the high mitogenic activity expressed as the stimulating effect on hamster lymphocyte proliferation [66]. Water and methanol extracts of S. aucuparia fruits were also effective in the inhibition of acetylcholinesterase (AChE) and exhibited in vitro cytotoxicity in SRB assay, using tumour HeLa, MCF7 and HT-29 and healthy MRC-5 cell lines; however, they didn't exhibit selectivity towards tumour cell lines [28].
The content of chlorogenic acid in sweet rowanberries can reach up to 200 mg/100 g, which is comparable with Arabica variety coffee beans, the richest source of this phenolic acid containing 280 mg/100 g [31]. Chlorogenic acids have been associated with a decreased risk of type 2 diabetes (T2D); they hydrolyse to caffeic acid, which reduces glucose absorption and oxidative stress in vitro and inhibits glucose-6-phosphate translocase, thereby decreasing glucose output in the liver. Intact chlorogenic acids are poorly absorbed in the small intestine, while the released after hydrolysis cinnamic acids are effectively absorbed with the help of enzymes in the colon depending on the precursor chlorogenic acid type and individual characteristics of a person [98]. Consequently, caffeoylquinic acid derivatives isolated from S. commixta fruits might be used for the regulation of diabetic complications and other pathogenic complications. These compounds also showed the most potent inhibitory effect against formation of the advanced glycation end products (AGE); neo-chlorogenic, crypto-chlorogenic, and chlorogenic acid exhibited potent inhibitory effects against peroxynitrite in radical scavenging assay [99].
Twenty-nine different extracts, fractions and residues obtained from S. domestica fruits, harvested at 5 maturity phases were assessed for their in vitro inhibitory capacity of a rate-limiting enzyme aldose reductase [36,47]. Diethyl ether and ethyl acetate fractions effectively inhibited aldose reductase and the effect was associated with the high content of flavonoids and hydroxycinnamic acid esters determined in the extracts by liquid chromatography with diode array detector and mass spectrometer (LC-DAD-MS). The authors concluded that consumption of S. domestica fruit might be a promising way to reduce the occurrence of long-term complications of T2D, particularly at the early disease stages. The fractions of diethyl ether, ethyl acetate and dichloromethane of S. domestica were also noted as potential antioxidants to be used in food and medicinal preparations [36,47]. In addition, Bailie et al. [11] suggested that both flavonoids and terpenoids could offer benefits to treat a number of T2D symptoms.
Several studies reported the effects of Sorbus bioactives on cancer cell lines and some disease biomarkers. Thus, vanillic acid 4-O-α-L-rhamnopyranoside, protocatechuic acid anhydride and trivanilloyl-(1,3,4-trihydroxybenzoyl) ester, which were the predominant antioxidants of the S. domestica fruits, make it potentially useful for the mitigation of several diseases, such as Clostridium difficile infection, inflammatory bowel and irritable bowel syndrome [101]. Ethanolic S. commixta fruit extract remarkably reduced the viability of human lung cancer cell lines through the induction of apoptosis irrespective of their p53 status [102]. Another study reported that ethyl acetate fraction of S. commixta exhibited considerable inhibition against thrombin, prothrombin, blood coagulation factors and platelet aggregation, without haemolysis activity at the doses up to 0.5 mg/mL and therefore, has the potential to be used as a new anti-coagulation agent [103]. The juice of S. sambucifolia provoked differentiation of HL-60 leukemic cells to monocyte/macrophage characteristics in a concentration-dependent manner as denoted by histochemical and biochemical assays; it was suggested that these findings are promising for developing new agents suitable for differentiation therapy of leukaemia with fewer side effects [70]. The S. umbellata (Desf.) Fritsch var. umbellata leaf extract demonstrated dose-dependent cytotoxic effect to A549 and MCF-7 cells in MTT assay, while the highest cell proliferation inhibition was observed for the A549, 71.8% at 150 µg/mL [104].
Sakuranetin isolated from S. commixta plant actively inhibited rhinovirus-3 (HRV3) replication and at 100 µg/mL exhibited higher than 67% antiviral activity without cytotoxicity in epithelioid carcinoma cervix (HeLa) cells; hence, it may be promising in developing novel drugs for treating HRV3 infections [105]. Water extract of the dried S. commixta inner stem bark suppressed the production of • NO and prostaglandins at the transcriptional levels, thus acting as an anti-inflammatory remedy for ear oedema formation, which was induced by arachidonic acid in mouse. A targeted blockage of protein kinase B translocation and its upstream signalling pathways was suggested as a possible therapeutic approach to develop anti-inflammatory drugs in the treatment of chronic diseases [84]. Furthermore, lupeol isolated, from the stem bark of S. commixta showed significant inhibitory effects on osteoclastogenesis; therefore, addition of S. commixta and lupeol could be used for bone diseases, such as osteoporosis, Paget's disease, osteolysis associated with periodontal disease, and multiple myeloma [38].
The treatment of S. commixta cortexes by β-glucanase increased extract antioxidant activity, while its application resulted in the enhanced viability of human dermal fibroblasts exposed to ultraviolet (UV) light [69]. Furthermore, Kim et al. tested the leaf extract of S. alnifolia, among the others, to develop new natural cosmetic ingredients with antioxidant activity. As a result, the trials proved that the extract of S. alnifolia exhibited 87% inhibition of elastase activity when applied at 1 mg/mL. This result may provide the relevant application of plant-based inhibitors of general elastase in cosmetics with effects for UV-irradiated and dry skin [106].
The methanol extracts of the dried stems and twigs of S. alnifolia contributed for protection against chemically and genetically induced dopaminergic neurodegeneration. Moreover, methanol extract of S. alnifolia plant increased food-sensing functions in the dopaminergic neuron degraded worms by 58.4% hereby prolonging the average lifespan by 25.6%. Therefore, the extract of S. alnifolia can be a useful candidate for the treatment of Parkinson's disease [26].

Conclusions and Further Perspectives
Polyphenolic antioxidants are among the most popular topics in characterisation of different Sorbus spp. anatomical parts. Since Sorbus polyphenols (proanthocyanidins, chlorogenic acid isomers and flavonols) are recognized as potent antioxidants and health beneficial phytochemicals, and considering the significant phenolic content in various Sorbus spp., it can be concluded that their products could be an excellent sources of natural antioxidants [54]. Such bioactives may be useful both for protecting foods against oxidation/microbial spoilage and providing health benefits to the consumers by incorporation of Sorbus preparations into functional foods, nutraceuticals and/or cosmeceuticals. The results of current review confirm the specific phenolic composition and antioxidant activity of different plant parts of numerous Sorbus spp. All parts of S. commixta, the fruit, leaves and inflorescences of S. aria, S. aucuparia, S. sambucifolia, the leaves and inflorescences of S. gracilis and S. koehneana and the leaves of S. wilfordii and S. pogonopetala may be distinguished as the materials demonstrating outstanding antioxidant effect.
However, more systematic studies are required for developing convenient and acceptable to consumer applications of Sorbus ingredients in foods and/or food supplements. Some studies have proved that the products of rowanberries demonstrate antioxidant activity and can be considered as a good source of antioxidants in the diet; however, these studies are not sufficient for wider applications of Sorbus. The production of functional foods and nutraceuticals from selected Sorbus spp. is envisaged to impart valuable biological effects, especially those related to immunity and health.