key: cord-0876117-25wqb8u0
authors: Młynarczyk, Karolina; Walkowiak-Tomczak, Dorota; Łysiak, Grzegorz P.
title: Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry
date: 2018-01-31
journal: Journal of Functional Foods
DOI: 10.1016/j.jff.2017.11.025
sha: 8d9e87521044563bb242155b525be3cc5bd491c3
doc_id: 876117
cord_uid: 25wqb8u0

Abstract European black elderberry naturally occurs in most of Europe and has been introduced into various parts of the world for fruit and flower production. Elderberry is rich in nutrients, such as carbohydrates, proteins, fats, fatty acids, organic acids, minerals, vitamins and essential oils. Elderberry also contains cyanogenic glycosides which are potentially toxic. Polyphenols, known for their free radical scavenging (antioxidant) activity, are the most important group of bioactive compounds present in elderberry in relatively high concentration. The high antioxidant activity of elderberry fruit and flowers is associated with their therapeutic properties. Elderberry has for a long time been used in folk medicine as a diaphoretic, antipyretic and diuretic agent. In recent years it was also found to have antibacterial, antiviral antidepressant and antitumour and hypoglycemic properties, and to reduce body fat and lipid concentration. Due to its health-promoting and sensory properties, elderberry is used primarily in food and pharmaceutical industry.

high in comparison to other fruits. The next one was malic acid (0.97-1.31 g/kg FW) and the remaining two acids were shikimic acid (0.14-0.93 g/kg FW) and fumaric acid (0.10-0.29 g/kg FW). Minerals are located both in berries and flowers. The mineral matter content represents 0.90-1.55% of the fruit mass, and includes K (2953-5494 mg/kg FW), P (735-1337), Ca (574-1528), Na (13-146), , .7), Zn (1.9-11.3), Mn (3.6-9.5), Cu (1.7-2.9). Additionally, berries contain also heavy metals such as lead (0.016-0.098 mg/kg FW) and cadmium (0.039-0.053), as well as nitrates (V) (2.63-3.21 mg/kg FW) and nitrates (III) (0.69-0.86) (Akbulut, Ercisli, & Tosun, 2009; Borowska, Zadernowski, Waźbińska, & Puczel, 2000; Diviš, Pořízka, Vespalcová, Matějíček, & Kaplan, 2015; Dulf, Oroian, Vodnar, Socaciu, & Pintea, 2013; Fazio, Plastina, Meijerink, Witkamp, & Gabriele, 2013; Kislichenko & Vel'ma, 2006; Kołodziej, Maksymiec, Drożdżal, & Antonkiewicz, 2012; Mratinić & Fotirić, 2007; Ognik, Rusinek, Sembratowicz, & Truchliński, 2006; Veberic, Jakopic, Stampar, & Schmitzer, 2009; Vulić, Vračar, & Šumić, 2008) . Elderberry fruit and flowers also include essential oils (around 0.01% in fruit), consisting of approx. 53 compounds in berries and 58 compounds in flowers (Kaack, 2008; .

With regard to vitamins present in S. nigra, several studies mention ascorbic acid, but the quantitative findings are pretty inconsistent. According to Kaack and Austed, the content of ascorbic acid ranges between 6 and 25 mg/100 g of elderberry fruit and depends on the cultivar. The highest content of this vitamin was found in 'Mammut' and the lowest-in 'Sambu' and 'Haschberg' (Kaack & Austed, 1998) . According to other studies, vitamin C content in wild elderberry is 13-35 mg/100 g and 28-34 mg/100 g, depending on the location (Akbulut et al., 2009; Mratinić & Fotirić, 2007) . Still others report a vitamin C concentration between 32.75-44.42 mg/100 g, with the highest content being found in the 'Samyl' cultivar and the lowest amounts in wild elderberries (Borowska et al., 2000; Vulić et al., 2008) . Furthermore, elderberry seed flour is a source of α-Tocopherol (0.49 µg/g of oil), which has the highest vitamin E bioactivity, as well as γ-Tocopherol (2.63 µg/g), which shows better antioxidant potential (Fazio et al., 2013) .

All parts of the elderberry contain cyanogenic glycosides, the most abundant of which are sambunigrin and prunasin. Furthermore, elderberry contains m-hydroxysubstituted glycosides, such as zierin and holocalin (DellaGreca, Fiorentino, Monaco, Previtera, & Simonet, 2000; Jensen & Nielsen, 1973) . These compounds are potentially toxic and life-threatening, because they can be hydrolysed resulting in the release of cyanide (Bromley, Hughes, Leong, & Buckley, 2005) . However, they occur primarily in unripe berries and are degraded during heat treatment (Williamson, Driver, & Baxter, 2009 ). The highest amounts of sambunigrin are present in elder leaves (27.68-209 .61 µg/g FW), lower amounts were found in flowers (1.23-18.88 µg/g FW), whereas berries contain the lowest amounts of this compound (0.08-0.77 µg/g FW). It was also found that the content of sambunigrin in elderberry changes depending on the growing altitude. The highest content of sambunigrin was recorded on a hilltop (1048 and 1077 m a.s.l.), which had lower temperatures and higher solar radiation as compared to other altitudes studied (209-858 m a.s.l.) (Senica, Stampar, Veberic, & Mikulic-Petkovsek, 2016) . Other toxic compounds present in elderberry are lectins sharing a high amino acids sequence homology and some of them having the N-glycosidase activity, which is typical for type II ribosome-inactivating proteins (RIPs). Type II RIPs occur in elderberry bark (e.g. nigrin b-SNA V, SNA I), fruit (nigrin f) and seeds (nigrin s) (Stripe, 2004; Tejero et al., 2015) . Moreover, elderberry contains the allergen Sam n1, which causes type 1 allergy and some tryptic peptides of Sam n1 demonstrate a high amino acid sequence with lectins and type 2 RIPs located in Sambucus 2013). However, it was discovered that incubation in a boiling water bath for 5-10 min, made lectins completely sensitive to hydrolytic enzymes in vitro and thus reduced the risk of allergenicity (Jiménez et al., 2017) .

The bioactive compounds found in elderberry are primarly polyphenols and anthocyanins (their content is presented in Table 1 ). The fruit of Sambucus nigra is an important source of phenolic compoundstheir content in the elderberries is relatively high in comparison to other fruits (Leja, Mareczek, & Nanaszko, 2007) . The main polyphenols in elderberry fruit are chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, quercetin, quercetin-3-rutinoside (rutin), quercetin-3glucoside (isoquercitrin), kaempferol-3-rutinoside, kaempferol-3-glucoside (astragaline), isorhamnetin-3-rutinoside and isorhamnetin-3glucoside. The primary flavonol in this plant is rutin, while the other flavonols, isoquercitrin and astragaline occur in elderberries in smaller amounts (Dawidowicz, Wianowska, & Baraniak, 2006; Kaack & Austed, 1998; Lee & Finn, 2007; Pietta et al., 1992; Veberic et al., 2009) . The concentration of quercetin measured in the fruit of thirteen elderberry cultivars ranged from 29 ('Gentofte') to 60 mg/ 100 g ('Haschberg') of fruit (Kaack & Austed, 1998) . Furthermore, Sambucus nigra berries contain small amounts of tannins with a low condensation degree. These are procyanidins, such as epicatechin (88.4% of total tannins) and catechin (11.6% of total tannins) and their thiol derivatives (Oszmiański & Moutounet, 1995) .

Phenolic compounds include anthocyanins, which are water-soluble glycosides or acylglycosides of anthocyanidins being oxygenated derivatives of flavylium salts (Prior, 2003) . They are well-known functional compounds used as food colorants, and they reduce the oxidative stress by scavenging free radicals, which makes them potential chemopreventive agents. Therefore, as excellent food colorants with antioxidative properties, anthocyanins are a good alternative to synthetic dyes due to their safety as well as potential nutritional and therapeutic effect (Bridle & Timberlake, 1997; Espín, Soler-Rivas, Wichers, & García-Viguera, 2000; Stintzing, Stintzing, Carle, Frei, & Wrolstad, 2002) .

Elderberry is a very rich source of anthocyanins in comparison to other fruits. The fruit of Sambucus nigra contains anthocyanins, especially cyanidin-3-glucoside and cyanidin-3-sambubioside. Two other (minor) anthocyanins are cyanidin-3,5-diglucoside, and cyanidin-3sambubioside-5-glucoside. In addition, trace quantities of cyanidin-3rutinoside, pelargonidin-3-glucoside and delphinidin-3-rutinoside were identified in the fruit of certain elderberry cultivars. Their content depends on cultivar/variety, ripening stage, growing season or kind and method of extraction (Borowska et al., 2000; Duymuş, Göger, & Hüsnü Can Başer, 2014; Fiorini, 1995; Kaack, 1997; Kaack & Austed, 1998; Lee & Finn, 2007; Leja et al., 2007; Pliszka, Waźbińska, Puczel, & Huszcza-Ciołkowska, 2005; Seabra, Braga, Batista, & de Sousa, 2010; Veberic et al., 2009; Youdim, Martin, & Joseph, 2000) . The cultivars most abundant in anthocyanins are 'Mammut', 'Samdal', 'Sampo' and 'Samyl', while 'Finn Sam', 'Haschberg', 'Allesoe', but also wild elderberry have the lowest quantities of these bioactive compounds. Total anthocyanin content varies almost threefold depending on the cultivar, e.g. 'Haschberg' was found to contain 664 mg of total anthocyanins/100 g, while the concentration of these compounds in 'Sampo' was 1816 mg/100 g. (Kaack, 1997; Kaack & Austed, 1998; Pliszka et al., 2005) . The polyphenol content changes at different stages of fruit ripening, and each compound shows its own individual change pattern during this process. The content of anthocyanins, especially cyanidin-3-sambubioside-5-glucoside, cyanidin-3sambubioside and cyanidin-3-glucoside, usually increases as berries ripen . The content of polyphenols and anthocyanins is also dependent on the growing season. Lee and Finn (2007) found that the total anthocyanin content in the fruit of 'Korsør' in 2005 was almost twice higher (343 mg of cyanidin-3-glucoside/100 g) than in 2004 (176 mg of cyanidin-3-glucoside/100 g). Total phenolic content was also much higher in 2005 (510 and 582 mg of gallic acid/100 g) than in 2004 (364 and 387 mg of gallic acid/100 g), respectively, for 'Haschberg' and 'Korsør'. The same applied to individual anthocyanins and almost all investigated polyphenols in the berries of both cultivars. The predominant anthocyanin found in elderberry juice concentrate or must is cyanidin-3-sambubioside, while cyanidin-3-glucoside was found to be the most abundant anthocyanin in elderberry wine (Bermúdez-Soto & Thomás-Barberán 2004; Schmitzer, Veberic, Slatnar, & Stampar 2010) and in the fruit of thirteen elderberry cultivars except 'Allesøe' (Kaack & Austed 1998) .

Alcoholic fermentation of berries causes changes in the content of phenolic compounds and anthocyanins, which also leads to colour changes. The concentration of polyphenols, such as neochlorogenic acid, chlorogenic acid, quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol-3-rutinoside, cyanidin-3-sambubioside-5-glucoside, cyanidin-3,5-diglucoside, cyanidin-3-glucoside or cyanidin-3-rutinoside, was observed to be higher in wine than in must, except cyanidin-3sambubioside, which significantly decreased during alcoholic fermentation. The storage and aging of elderberry wine resulted in the decrease in the content of each analysed compound, and after three years the total phenolic content fell by 21%, whereas the total anthocyanins content was lower even by 94% compared to the young wine. Due to the degradation of anthocyanins, the colour of elderberry wine also changed from bright-red to brown-red hues. Antioxidant activity was also higher in young wine than in must and dropped after aging (Schmitzer et al., 2010) .

The method of juice production affects the content of bioactive compounds. For instance, elderberry juices processed using enzymatic treatment (pectinolysis) demonstrated a lower average content of most investigated phenolic compounds compared to the juices produced without enzymatic treatment .

The content of anthocyanins in elderberry products is affected by pH, storage time and storage temperature. It was observed that the extension of storage time and increase in pH and storage temperature resulted in the decrease in the content of anthocyanins in elderberry juice concentrate (Walkowiak-Tomczak, Czapski, & Młynarczyk, 2016) .

Elderberry pomace, although it makes up 25-40% of total fruit weight, is very rich in anthocyanins: it contains 75-98% of total anthocyanins found in fresh elderberries (Brønnum-Hansen, Jacobsen, & Flink, 1985) . The major anthocyanin in elderberry pomace is usually cyanidin-3-glucoside (14-78 mg/g DW) and the sum of this compound and cyanidin-3-sambubioside (15-61 mg/g DW) represents approximately 90% of the total anthocyanin content, which ranges from 39 to 153 mg/g of dry matter, depending on the extraction method. On the other hand, the content of rutin in elderberry pomace is 6-14 mg/g DW (Seabra et al., 2010) .

Sambucus nigra flowers contain even higher amounts of phenolic compounds in comparison to the fruit and leaves of this species * Abbreviation: GAEgallic acid equivalents, CAEcaffeic acid equivalents, ChAEchlorogenic acid equivalents, CGEcyanidin-3-glucoside equivalents, CSEcyanidin-3-sambubioside equivalents, DWdry weight FWfresh weight. (Dawidowicz et al., 2006; Kołodziej & Drożdżal, 2011) . The main group of phenolic compounds found in elderflowers are hydroxycinnamic acids, the most important of which is chlorogenic acid. Other hydroxycinnamic acids present in elderflowers include, among others, neochlorogenic acid, cryptochlorogenic acid, 3-and 5-feruloylquinic acid, and dicaffeoylquinic acids, including notably 1,5-Di-caffeoylquinic acid. The second important group of polyphenols comprise flavonols, from which several glycosides of quercetin, kaempferol and isorhamnetin were detected in elderflower extracts. The major polyphenol from this group is quercetin-3-rutinoside (rutin). This flavonol together with kaempferol-3-rutinoside and isorhamnetin-3-rutinoside constitute more than 90% of total flavonoids in most analysed genotypes. Other groups of phenolic compounds occurring in elderflowers are flavanols, which include catechin, epicatechin and procyanidin trimer, and flavanones, e.g. naringenin. Elderflowers contain more of certain phenolic compounds (rutin, isoquercitrin and astragaline) than berries or leaves Dawidowicz et al., 2006; Mikulic-Petkovsek, Samoticha, Eler, Stampar, & Veberic, 2015) . The content of phenolic compounds in elderflowers, similarly to elderberries, depends on the genotype as well as on liquid composition and extraction conditions. For instance, the highest content of chlorogenic acid was found in the Virum genotype (20.7 mg/g DW), while the lowest in the Sambu genotype (10.1 mg/g DW). On the other hand, the Samocco genotype was shown to have the highest (42.3 mg/g DW) whereas the Jaegerspris genotype the lowest (11.6 mg/g DW) concentration of rutin . Moreover, the highest content of flavonols in elderflowers was a result of higher temperature of extraction -214.25 and 139.32 g/100 g extr. for 100°C and 20°C, respectively (Dawidowicz et al. 2006 ).

Elderberry fruit is characterized by high antioxidant activity, which ranges from 82.08 to 89.25% of inhibition in relation to the DPPH radical. The antioxidant properties of elderberries are primarily attributable to the presence of phenolic compounds and depend largely on the chemical structure of molecules and composition of individual berries (Pliszka et al., 2005; Rice-Evans, Miller, & Paganga, 1996; Zheng & Wang, 2003) . Anthocyanins significantly influence the antioxidant activity of elderberries. With the increase of anthocyanin concentration the antioxidant activity also increases, but only to a certain level above which this parameter starts to fall (Pliszka et al., 2005) .

According to Duymuş et al., elderberry extracts show antiradical activity (towards DPPH), but not as strong as ascorbic acid used as standard. The IC 50 value (concentration needed to scavenge 50% of free radicals) was 117 µg/ml for 70% acetone extract and 123 µg/ml for water extract of elderberry, while it was 8 µg/ml for ascorbic acid. As for TEAC values (ABTS radical scavenging activity), these ranged from 0.89 (acidified methanol extract) to 1.96 mmol Trolox equiv./l (70% acetone extract) and the highest value was almost the same as for ascorbic acid (1.97 mM). Additionally, the TEAC value for cyanidin-3glucoside standard was nearly the same as for water extract (1.87 and 1.85 mM, respectively). Elderberries are also able to inhibit the linoleic acid oxidation. The highest inhibition rate (58%) was observed for 70% ethanol extract; however, none of the analysed elderberry extracts was as active as BHT control (Duymuş et al., 2014) . A commercial concentrate of elderberry fruit demonstrated lower radical scavenger capacity towards DPPH compared to other studied sources of anthocyanins (extracts of fresh chokeberries, blackthorn fruit and strawberries) and natural and synthetic antioxidants (α-tocopherol, BHT and BHA) (Espin et al., 2000) .

The antioxidant potential of elderberry was also investigated in in vitro cultured human colonic mucosa cells. An elderberry extract at a concentration of 1 mg of freeze-dried elderberry powder/ml reduced the excessive intracellular reactive oxygen species production by 22% and oxidative DNA damage by 46% in the colonic cells. Additionally, the inhibition of oxidant-induced mutagenicity by 26% in the Salmonella typhimurium strain was observed. These results indicate that elderberry fruit is able to protect colon cells against the harmful effects of oxidative stress (Olejnik et al., 2016) .

Flowers of Sambucus nigra usually have higher antioxidant activity than berries and leaves. According to Kołodziej and Drożdżal, T EC50 (time required to reduce the initial DPPH concentration by 50%) was 23-75 s for flowers, whereas T EC50 for fruit was 91-133 s. In another study, elderflowers exhibited stronger DPPH radical inhibition activity (91.95-94.15%) in comparison to berries (50.25-67.69%) and leaves (16.76-48.52%). These values also depended on the temperature of alcoholic extraction-in each case, extraction at a temperature of 100°C resulted in a higher percentage rate of free radical inhibition than extraction at a lower temperature (20°C) (Dawidowicz et al., 2006; Kołodziej & Drożdżal, 2011) . The results obtained by Stoilova et al. demonstrate that the extract of elderflowers possess greater radical scavenging properties in comparison to rutin, BHT and BHA used as standards. Elderflower extract showed the highest inhibition of DPPH (97.70%) at the lowest concentration (10 µg/ml) in comparison with the standards (77.47; 82.40; 89.98% and 40; 20; 20 µg/ml, respectively) and the IC 50 concentration of S. nigra extract for the inhibition was the lowest (0.152 µg/ml) compared to IC 50 of rutin, BHT and BHA (14.65; 4.407; 1.120 µg/ml, respectively). In addition, this extract eliminated the highly reactive hydroxyl radicals, thus preventing the deoxyribose degradation, more effectively as compared to rutin and quercetin (IC 50 = 0.0122; 0.505; 4.61 µg/ml, for elderflower, rutin and quercetin extracts, respectively). Furthermore, extract of elderflowers showed metal-chelative properties, preventing the initiation of hydroxyl radicals, that were also stronger than those of rutin and quercetin standards (Stoilova, Wilker, Stoyanova, Krastanov, & Stanchev, 2007) .

In a study which investigated the metabolism of various anthocyanins after oral administration of elderberry juice, small amounts of Sambucus nigra anthocyanins were identified in human urine. Seven volunteers took 4 g of spray-dried elderberry juice, corresponding to 50 ml of fresh juice and containing 500 mg of anthocyanins (12.5%). Several peaks appeared in the chromatogram and two of them had the same retention time as the major cyanidin-3-glucoside and cyanidin-3sambubioside from juice. Only 0.04% of the consumed cyanidin-3sambubioside and 0.01% of cyanidin-3-glucoside were excreted into urine and the highest excretion of anthocyanins was noted 3-4 h after the intake of elderberry juice. Even lower amounts of unmetabolized cyanidin-3,5-diglucoside and cyanidin-3-sambubioside-5-gluside were identified in a few samples; however, other substances shown in the chromatogram that were possible metabolites of Sambucus nigra anthocyanins were not identified (Murkovic, Mülleder, Adam, & Pfannhauser, 2001) . According to another study concerning the absorption of anthocyanins, these antioxidants are ingested by humans in their original, unchanged glycosylated forms. The content of anthocyanins in blood plasma and urine was analysed in four women treated with 12 mg of elderberry extract, containing 720 mg anthocyanins consisting mainly of cyanidin-3-sambubioside and cyanidin-3-glucoside. The blood plasma samples, which were collected before and between 10 min and 24 h after the consumption of the extract exhibited at least five additional anthocyanin-like compounds, primarily cyanidin-3sambubioside and cyanidin-3-glucoside. The levels of all detected compounds decreased after 1 h, disappearing after 24 h. Their maximum concentration in blood plasma was reached within 72 min after the intake, and its average value was 97.4 nmol/l of total anthocyanins. In the urine samples, collected before and between 0 and 24 h after the intake, at least six compounds were detected at 520 nm after extract consumption, and the major anthocyanins were also cyanidin-3-sambubioside and cyanidin-3-glucoside. Most anthocyanin-like compounds appeared in urinary excretion during the first 4 h. The total amount of the anthocyanins excreted during 24 h after the intake of the elderberry extract was 397.0 µg of cyanidin-3-glucoside equivalents, while the average excretion rate of these compounds during the first 4 h was 77.2 µg/h and during the second 4 h-13.4 µg/h (Milbury, Cao, Prior, & Blumberg, 2002) . In a study by Bitsch et al., cyanidin glucosides and glucuronides were detected in urinary excretion. Seven healthy volunteers consumed 150 mL of elderberry juice concentrate which contained 3.57 g of total anthocyanins. Within 5 h after the ingestion of the juice dose, the urinary excretion of total cyanidin glucosides (cyanidin-3,5diglucoside, cyanidin-3-sambubioside, cyanidin-3-glucoside) and their glucuronide conjugates was 1.876 mg of cyanidin-3,5-diglucoside, which constituted 0.053% of the administered dose. The percentage of the excreted glucuronides was only 0.003%, while the share of the glucuronides in relation to all excreted anthocyanins was 6.2%. The maximum excretion rate of anthocyanins was reached after one hour of intake, followed by a sharp drop (Bitsch et al., 2004) . In another study, the urinary excretion, the plasma concentration of elderberry anthocyanins as well as other antioxidant parameters were determined. Eight participants received doses of elderberry juice (200, 300 and 400 ml) in separate treatments. The total anthocyanin content, including cyanidin-3-sambubioside and cyanidin-3-glucoside, in urinary excretion increased with the increase in the juice dose taken. The lowest elderberry juice dose (200 ml), which contained 361 mg of total anthocyanins, caused the excretion of, on average, 41.4 µg/h of anthocyanins, while after the highest dose (400 ml) containing 722 mg of total anthocyanins, the average urinary excretion of these compounds was 113.2 µg/h. Within 7 h, the values of the fraction of orally ingested total anthocyanins in urinary excretion were 0.033, 0.038 and 0.040% after the intake of 200, 300 and 400 ml of juice, respectively. The aim of the second treatment was to investigate the effect of the intake of 400 ml elderberry juice or water (control) on the content and antioxidant capacity of total phenolics and anthocyanins and of ascorbic and uric acid in blood plasma. Both the content and the antioxidant activity of total phenolics and anthocyanins increased after juice ingestion, reaching the highest level 1 h after the intake, whereas the values of these parameters did not change in the control group. At the same time, the concentrations of ascorbic and uric acid were unaffected by the elderberry juice or water intake (Netzel et al., 2005) . Czank et al. found that the bioavailability of anthocyanins was higher and the diversity of their metabolites was greater than previously thought. Eight healthy male participants received 500 mg bolus dose of isotopically labelled cyanidin-3-glucoside (6,8,10,3′,5′-13C5-cyanidin-3-glucoside) and their samples of blood, urine, breath and faeces were examined within 48 h after the ingestion. The average recovery of 13C in breath, urine and faeces was 43.9% and the relative bioavailability from urine and breath was 12.38%. The 13C labelled metabolites consisted of 24 compounds and included phase II conjugates of C3G and cyanidin, degradants, phase II conjugates of protocatechuic acid, phenylacetic acids, phenylpropenoic acids and hippuric acid. The metabolites reached a 42fold peak of serum concentration relative to 13C5-C3G, and were detected much later than the parent anthocyanin (Czank et al., 2013) . The results of the above-mentioned studies on the bioavailability of elderberry antioxidants are summarized in Table 2 .

Flowers and berries of Sambucus nigra are known as a traditional remedy for various kinds of ailments and diseases and both are commonly used in folk medicine (Kohlmünzer, 1998) . They are primarily used to treat common symptoms related to cold, feverish conditions, coughing, nasal congestion, mucous discharge and influenza, as well as a preventively to strengthen the immune system (Elliman, 1994; Grieve, 1971; Hoffmann, 1990 ; The ABC Clinical Guide to Elder Berry). Due to the presence of flavonoids, elderflowers demonstrate primarily diaphoretic, antipyretic and diuretic properties. They obturate the capillary walls, improve their flexibility and prevent infiltration of red blood cells and plasma outside the vessels thanks to the content of compounds (rutin) having the properties of vitamin P. Moreover, elderflowers show anti-inflammatory and antibacterial properties and therefore are used for gargling to treat sore throats or as compresses to treat conjunctivitis. They are most often used as infusions of dried flowers for internal or external application. The fruit of Sambucus nigra, similarly to flowers, exhibits diaphoretic, antipyretic and diuretic properties, but apart from that it act as a laxative and detoxifier, hence elderberries are often a component of herbal mixtures used as a remedy for constipation or to help slimming. In addition, elder fruit demonstrates a moderate analgesic effect and can be used as an adjuvant painkiller against migraine, sciatica and neuralgic pains (Beaux, Fleurentin, & Mortier, 1999; Bown, 1995; Grieve, 1984; Ożarowski & Jaroniewski, 1987; Schmersahl, 1964) . Not only elder flowers and berries are beneficial to health, but also bark, root, stem and leaves of Sambucus nigra have been used especially by the rural population as medicine or food. For instance, elder bark has been known for its diuretic and slimming properties, while elder leaves may help strengthen resistance to infectious diseases (Baytop, 1984; Wójcik, 2002) . Nowadays remedies against cold, flu and other infectious illnesses are being developed using Sambucus nigra fruit or flowers. Thole et al. used mass spectrometry and liquid chromatography-mass spectrometry to demonstrate the chemopreventive potential of elderberry. It was found that elderberry fruit extract, or rather an extract fraction that in addition to the phenolic compounds included e.g. iridoid monoterpene glycosides, phytosterols and sesquiterpenes, caused a strong induction of quinone reductase and inhibition of cyclooxygenase-2. This indicates antitumor activity of Sambucus nigra fruit, especially that preventing the initiation and promotion of cancerogenesis stages (Thole et al., 2006) . The results of the studies on the health-promoting properties of elderberry are shown in Table 3 (in vitro) and in Table 4 (in vivo).

The antibacterial activity of elder flowers, berries and leaves (aqueous or ethanol extracts of freeze-dried elder concentrates) was studied against 13 nosocomial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), which is known as a clinically significant pathogen connected with infections of skin and soft tissue. Despite a 100-fold dilution, ethanol extracts of both elder flowers and berries exhibited inhibitory activity for most of the analysed bacteria, both Gram-positive, such as Staphylococcus sp. or Bacillus cereus, and Gramnegative, such as Salmonella poona or Pseudomonas aeruginosa. Elderflower extracts displayed a higher antimicrobial efficacy and larger zones of inhibition against a broad range of bacteria, particularly MRSA (17 mm) or Pseudomonas aeruginosa (9 mm), than other extracts. A ten-fold diluted aqueous extract of elder leaves showed moderate activity against the development of Bacillus cereus and Serratia marcescens (6 mm), but was not able to inhibit the growth of any crucial nosocomial pathogens (Hearst et al., 2010) . Sambucus nigra fruit possesses antimicrobial activity against human pathogenic bacteria that cause infections of the upper respiratory tract. The addition of (Rubini®), a standardized liquid extract of elderberry, at a concentration of 10%, to bacterial liquid cultures decreased the growth of Gram-positive bacteria strains of Streptococcus pyogenes and Streptococcus Group C and G, as well as Gram-negative bacteria Branhamella catarrhalis, by more than 70% compared to the control samples. A concentration of 20% of the elderberry extract inhibited the bacterial development by 99% (Krawitz et al., 2011) .

The antiviral activity of Rubini® was investigated against two different human pathogenic virus strains, such as influenza A (KAN-1,  H5N1) and B (B/Mass), in the Madin-Darby canine kidney cell culture (Fig. 1) . Treatment with elderberry extract distinctly reduced the spread of the foci size of influenza B virus, whereas the foci size of KAN-1 was enlarged, but its number was reduced in comparison to the untreated control (Krawitz et al., 2011) . It was found that the elderberry extract at a concentration of 252 µg/ml caused a 50% inhibition (IC 50 ) of human influenza A (H1N1) virus applied to infect the Madin-Darby canine kidney (MDCK) NBL-2 cells, while a concentration of 1000 µg/ ml allowed a 100% inhibition of this virus infection. In addition, it was shown that phenolic compounds from the elderberry fruit extract bind to H1N1 virions, thus blocking their ability to infect host cells. Two compounds which bind to H1N1 were identified: 5,7,3′,4′-tetra-O-methylquercetin and 5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl) chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate (Fig. 1) . Both compounds were synthesized and it was demonstrated that compound 1 achieved an IC 50 of 0.13 µg/ml for inhibition of H1N1 infection, and dihydromyricetin corresponding compound 2 gave an IC 50 of 2.8 µg/ ml. The mechanism of action was shown in Fig. 2 . Taking into account these parameters, the effect of elderberry flavonoids related to inhibition of H1N1 is comparable to that of the known anti-influenza medicines, such as Oseltamivir (Tamiflu®) and Amantadine (Roschek, Fink, McMichael, Li, & Alberte, 2009 ). In another study in which MDCK was used as well, it was observed that concentrated elderberry juice could affect H1N1 in the early stages of viral replication: IC 50 was achieved with an extract concentration of 720 µg/ml when the samples were given during infections, and with an extract concentration of 3600 µg/ ml when the samples were applied immediately after infection. Additionally, in vivo experiments showed that elderberry effectively suppressed viral replication and could stimulate the immune response. Concentrated elderberry juice was separated in three fractions (low, medium and high molecular weight) that were administered to infected mice. The most effective fraction was the high-molecular-weight fraction (HM), which suppressed the viral yield in the bronchoalveolar lavage fluids (BALFs) and lungs. Fraction II, which was isolated from HM and contained mainly acidic polysaccharides, caused an increase in the level of IFV specific neutralizing antibody in the BALFs and serum and also the level of the secretory IgA in the BALFs and feces. The mediummolecular-weight fraction, which was rich in polyphenols, showed a lower activity (Fig. 1) (Kinoshita et al., 2012) . Furthermore, elderberry extracts demonstrate an inhibitory effect on infectious bronchitis virus (IBV), a pathogenic chicken coronavirus, at an early stage of the virus infection. Elderberry extract reduced IBV titers by several orders of magnitude, in dependence of the dose applied. The increase in the elderberry extract concentration caused a decrease in virus titers and vice versa. In addition, electron microscopy of virions that were treated with elderberry extract demonstrated compromised envelopes and the presence of membrane vesicles. There are data that indicate that the pretreatment with elderberry extract of IBV infection leads to damage to the virus extensive membrane and probably renders the virus non-infectious (Chen et al., 2014) . Antiviral activity of elder bark was evaluated in relation to feline immunodeficiency virus (FIV), which frequently occurs in domestic cats and from the point of view of biological and pathogenic functions is very similar to the human immunodeficiency virus (HIV). It was shown that elder bark extract had a high activity against FIV because it inhibited syncytia formation, with the inhibition level being dependent on extract concentration. Syncytia inhibition level of 100% was achieved when the extract concentration was 500 µg/ml (Uncini Manganelli, Zaccaro, & Tomei, 2005) .

Considering clinical trials randomized, double-blind and placebocontrolled research concerning influenza A and B virus infections was carried out in the autumn/winter season 1999/2000 in Norway (Fig. 1) . The study was attended by humans suffering from at least two symptoms of flu including fever ≥38°C and one or more respiratory influenza symptoms. The study used a standardized elderberry extract, the Sambucol® syrup. The participants, who were randomly divided into two groups, received either 15 ml of the elderberry syrup or placebo four times a day during five days. The effects of the treatment were monitored by a visual analogue scale. It turned out that in the group treated with the elderberry syrup, symptoms ebbed on average four days earlier than in the placebo group (Zakay-Rones et al., 2004) . In 2009, during the spring flu season, a randomized, short-term, doubleblind and placebo-controlled clinical trial was conducted with participants who showed three or more flu symptoms, such as fever, coughing, headache, muscle aches, nasal mucus discharge or nasal congestion, for less than 24 h (Fig. 1) . The patients were divided at random into two groups. The first group received 4 slow-dissolve lozenges of a proprietary elderberry extract a day (each lozenge contained 175 mg of the proprietary elderberry extract) and the second group received placebo lozenges. After 48 h of treatment, patients from the group treated by elderberry extract demonstrated significant reduction in most of the flulike symptoms -28% of patients were void of all symptoms and 60% of patients received relief of some symptoms and had one or two mild symptoms, whereas the placebo group demonstrated either no improvement or even aggravated symptoms (Kong, 2009) . Selected antiviral properties of elderberry fruit (regarding to influenza A and B virus) are illustrated in Fig. 1 .

Elder may be an effective traditional remedy for diabetes, and as such, it could be used as a dietary adjunct in diabetes treatment. It was found that water-soluble compounds included in elder flowers were able to directly stimulate glucose metabolism and promote insulin secretion through clonal pancreatic β-cells. An extract of elder flowers (1 g/L) significantly increased glucose uptake, glucose oxidation and glycogenesis in vitro in mice abdominal muscles without added insulin (Gray, Abdel-Wahab, & Flatt, 2000) . The fruit of Sambucus nigra positively influences the treatment of diabetic osteoporosis. A polyphenolic extract of elderberry improved the bone mineral density and reduced the body fat of diabetic rats. Also, the antioxidative capacity of serum improved in rats treated with the polyphenolic extract as the concentration of reduced glutathione (GSH) was restored to normal. The concentration of malondialdehyde, which is an index of the lipid peroxidation level, decreased in the serum, thus resulting in an improved osteoporosis status (Badescu, Badulescu, Badescu, & Ciocoiu, 2012) . Salvador et al. investigated the effect of elderberry lipophilic and polar extract supplementation on diabetes management indices in rats. Type 2 diabetic rats (induced by streptozotocin) were fed a high-fat diet and received for 4 weeks 190 and 350 mg/kg body weight/day doses of lipophilic and polar elderberry extract, respectively. The polar extract lowered fasting blood glucose, whereas the lipophilic extract decreased secretion. Both extracts reduced insulin resistance and no significant alterations in the hematological indices, sera lipids and trace elements homeostasis from sera and tissues were observed (Salvador et al., 2017) . Farrel et al. studied the effect of anthocyanin-rich elderberry extract on metabolism in a diet-induced obese mouse model. Four types of diet were used for 16 weeks: low-fat diet (LFD), high-fat lard-based diet (HFD), HFD with 0.25% of elderberry extract and HFD with 1.25% of elderberry extract. It was found that both groups of mice which received elderberry extract were characterized by a significantly lower liver weight and serum TAG concentration, and by significantly lower serum inflammatory markers, insulin resistance and hepatic fatty acid synthase mRNA, in comparison to HFD. In addition, HFD with 1.25% of elderberry extract reduced liver cholesterol and PPARγ2 mRNA compared to HFD and HFD with 0.25% of elderberry extract (Farrel, Norris, Ryan et al., 2015) . Furthermore, supplementation with 1.25% of elderberry extract of hyperlipidemic mice was conducted in order to determination the effect on atherosclerosis and HDL dysfunctions. It Table 3 Medicinal potential of elderberry (Sambucus nigra) preparationsin vitro studies.

Antibacterial activity Ethanol extract of elder flowers and berries Inhibitory activity for most of the 13 nosocomial pathogens (e.g. At least 3 L of elderberry juice, 3 Sambucus nigra tablets and 9

Asparagus officinalis tablets/day 15 days The BMI index dropped by approx. 3%, the weight fell by an average of 3.2 kg, systolic blood pressure decreased by an average of over 5% and diastolic blood pressure by 2.5% Chrubasik et al. (2008) Effect on weight reduction and urinary parameters 11 volunteers Diluted (1:5) concentrate of elderberries (from 120 g of berries) and flowers (flower juice and extract from 3.9 g of dried flowers)

200 ml divided into up 6 portions 7 days An average weight reduction was 2.6 kg; no effect on pH, hydrogen ion concentration and 24 h hydrogen excretion in urine; no effect on the solubility of stone-inducing ions Walz and Chrubasik (2008) (continued on next page)

was not observed significantly differences in serum lipids between elderberry and control group, however, aspartate transaminase and fasting glucose were decreased in elderberry group of mice. Hepatic and intestinal mRNA changes with an improvement in HDL function and a decrease in hepatic cholesterol levels were also reported in elderberryfed mice. Additionally, this group showed significantly higher activity of serum paraxonase-1 arylesterase. The results indicate the reduction of elderberry in aorta total cholesterol content and then less atherosclerosis progression (Farrel, Norris, Lee, Chun, & Blesso, 2015) . A randomized, placebo-controlled and double-blind study was conducted to determine the impact of anthocyanins obtained from elderberry juice on the lipid and antioxidant status. 34 healthy volunteers received 400 mg of spray-dried elderberry powder in gelatinous capsules or placebo three times a day during 2 and 3 weeks. Each capsule contained 10% anthocyanins and represented the equivalent of 5 ml of elderberry juice. Furthermore, an additional trial was carried out to study the short-term effect of elderberry anthocyanins on serum lipid concentration, where six volunteers received a single dose of 10 capsules, which was the equivalent of 50 ml of elderberry juice. In the placebo-controlled study, the elderberry group did not show statistically significant differences in changes in serum lipids as well as vitamin A, E and β-carotene, compared to the placebo group, and even, a decrease in the level of vitamin C was observed in both groups. In a single-dose experiment conducted as part of the same study, an increase in total anthocyanins in serum was found during the postprandial phase. The serum lipids concentration was lower in the elderberry group, but differences were not significant (Murkovic et al., 2004) . In a study in which patients took, among others, dietary supplements from the fruit and flowers of Sambucus nigra, the BMI index dropped by approx. 3%, the weight fell by an average of 3.2 kg, systolic blood pressure decreased by an average of over 5% and diastolic blood pressure by 2.5%. Moreover, physical and mental well-being as well as the quality of life of the patients significantly improved . A diluted concentrate from elder berries and flowers, used among others in hypocaloric diet in Switzerland, resulted in average weight loss of 2.6 kg in 11 volunteers during 7 days of diet (Walz & Chrubasik, 2008) . Mahmoudi et al. (2014) evaluated the antidepressant activity of elderberry extracts by exposing mice to the forced swimming test (FST) and the tail suspension test (TST). The tests demonstrated very good antidepressant properties of the extract tested: it shortened the immobility time and increased the activity of mice which were given the extract as compared to the control group, with the immobility time and activity level being dependent on the extract dose. Moreover, elderberry extract at a dose of 1200 mg/kg caused a far higher activity of mice in the FST than imipramine (10 mg/kg), a strong and effective antidepressant drug (Mahmoudi et al., 2014) .

Research on the impact of some proprietary elder concentrate on the urinary electrolyte balance showed that 200 ml of concentrate made from fresh berries, flower juice and dried flower extract, did not influence pH, hydrogen ion concentration and 24 h hydrogen excretion in urine collected from 11 participants. Elderberry concentrate also had no impact on the solubility of stone-inducing ions, which suggests that it can be used in patients with idiopathic nephrolithiasis without any risk of harm (Walz & Chrubasik, 2008) . Elderberry as a dietary supplement in the form of capsules containing flower extract had no apparent inhibitory effect on uridine diphospho-glucuronosyltransferase (UGTs). IC 50 values were higher than 500 µg/mL for all the five studied UGTs enzymes in vitro, such as UGT1A1, UGT1A4, UGT1A6, UGT1A9 and UGT2B7 (Choi, Park, Yoon, & Bae, 2014). (Kinoshita et al., 2012; Kong, 2009; Krawitz et al., 2011; Roschek et al., 2009; Zakay-Rones et al., 2004) .

Sambucus nigra L. K. Młynarczyk et al. Journal of Functional Foods 40 (2018) 377-390 13. Industrial uses of elderberry

Being rich in anthocyanins, elderberry belongs to several berry species that are used as natural colorants in different industries. Particularly, elderberry fruit is used as a food colorant, an ingredient in pharmaceuticals, concentrates, juices, syrups, jams, jellies, powders and other food preserves, a filling in pies, cakes or desserts, and also for the production of alcoholic beverages, such as wine (Bermúdez-Soto & Thomás-Barberán, 2004; Inami, Tamura, Kikuzaki, & Nakatani, 1996; Kaack, Christensen, Hughes, & Eder, 2005) . Elderberry pomace, which is a waste by-product of juice production, is an important raw material used in the production of anthocyanin extracts and lyophilized dyes. It is also used as animal feed and organic fertilizer (Kaack, 1990; Seabra et al., 2010) .

Elderflowers, similarly to berries, are also widely used in food industry. They are natural flavouring components in alcoholic and nonalcoholic beverages, sparkling, bitter and white wine, fruit brandies and various spirits, as well as in tea and products like yoghurt or ice cream (Fazio et al., 2013; Kaack, Christensen, Hughes, & Eder, 2006) .

According to a 2010 report by the European Herb Growers Association, Sambucus nigra (flowers and berries) was the most harvested medicinal plants intended for export trade and for tea and phytopharmaceutical production in Bulgaria and Romania (European Herb Growers Association (Europam), 2010). Elderberry ranked as the 18th best-selling herbal dietary supplement on the medicine, food and mass market in the USA in 2011 (Engels & Brinckmann, 2013) .

Numerous studies indicate that the fruit and flowers of Sambucus nigra are highly nutritious and rich in bioactive compounds such as polyphenols and anthocyanins. Thanks to these compounds, elderberry is characterized by high antioxidant activity, which significantly affects its health-promoting properties. It was shown that elderberry has mainly antibacterial and antiviral properties, can reduce sugar and lipid concentration, and even exhibit antidepressant and antitumour properties. Most studies have focused on the antiviral properties of elderberry fruit, so there is a high need for further research into the other properties of this valuable plant. Considering the growing fashion for natural, organic and health-promoting food, it can be concluded that elderberry as a natural component of food products fits perfectly into this trend and has a good chance to increase its role as a beneficial component of a healthy diet.

Physico-chemical characteristics of some wild grown European elderberry (Sambucus nigra L.) genotypes

Sambucus nigra L. Biological flora of the British Isles

Mechanism by Sambucus nigra extract improves bone mineral density in experimental diabetes

Türkiye Bitkiler ile Tedavi (Geçmişte ve Bugün)

Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats

Evaluation of commercial red fruit juice concentrates as ingredients for antioxidant functional juices

Urinary excretion of cyanidin glucosides and glucuronides in healthy humans after elderberry juice ingestion

Charakterystyka chemiczna owoców bzu czarnego (Sambucus nigra L.). Roczniki Akademii Rolniczej w Poznaniu

Encyclopaedia of herbs and their uses

Anthocyanins as natural food colours-selected aspects

Life-threatening interaction between complementary medicines: Cyanide toxicity following ingestion of amygdalin and vitamin C

Anthocyanin colourants from elderberry (Sambucus nigra L.). 1. Process considerations for production of the liquid extract

Growing and marketing elderberries in missouri

Elderberry: Botany, Horticulture, Potential

Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry and raspberry ketones) commonly used as a herbal supplements to inhibit uridine diphospho-glucuronosyltransferase

Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of elderflower extracts rich in flavonoids and phenolic acids

An observational study and quantification of the actives in a supplement with Sambucus nigra and Asparagus officinalis used for weight reduction

Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: A 13 Ctracer study 1-3

The antioxidant properties of alcoholic extracts from Sambucus nigra L. (antioxidant properties of extracts). LWT -Food Science and Technology

Cyanogenic glycosides from Sambucus nigra

Elemental composition of fruits from different black elder (Sambucus nigra L.) cultivars grown in The Czech Republic

Obst, gemüse, gartenbau. Wiesbaden: Statistisches Bundesamt. Accesed 2016-11-26 at

Lipid classes and fatty acid regiodistribution in triacylglycerols of seed oils of two Sambucus species (S. nigra L. and S. ebulus L.)

In vitro antioxidant properties and anthocyanin compositions of elderberry extracts

Vegetation ecology of Central Europe

Elderberry, flu contrary

European elder. Herbal Gram

Anthocyaninbased natural colorants: A new source of antiradical activity for foodstuff

Production of medicinal and aromatic plants in Europe status 2010

Anhocyanin-rich black elderberry extract improves markers of HDL function and reduces aortic cholesterol in hyperlipidemic mice

Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice

Comparative analyses of seeds of wild fruits of Rubus and Sambucus species from Southern Italy: Fatty acids composition of the oil, total phenolic content, antioxidant and anti-inflammatory properties of the methanolic extracts

Evaluation of American (Sambucus canadensis) and European (S. nigra) elderberry genotypes grown in diverse environments and implications for cultivar development

Preparative high-performance liquid chromatography for the purification of natural anthocyanins

Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins

Polyphenols: A nutraceutical approach against diseases. Recent Patents on Food

The traditional plant treatment, Sambucus nigra (elder), exhibits insulin-like and insulin-releasing actions in vitro

A modern herbal

A modern herbal

Antibacterial activity of elder (Sambucus nigra L.) flower or berry against hospital pathogens

The new holistic herbal

Holunderanbau -Was kann wie erreicht werden

Atlas of North European vascular plants north of the tropic of cancer

Stability of anthocyanins of Sambucus canadensis and Sambucus nigra

Sambucus L. Taxonomic serial no.: 35315. Integrated taxonomic information system

Cyanogenic glucosides in Sambucus nigra L

Isolation and molecular characterization of two lectins from dwarf elder (Sambucus ebulus L.) blossoms related to the Sam n1 allergen

Lectin digestibility and stability of elderberry antioxidants to heat treatment in vitro

Differential sensitivity of D-galactose-binding lectins from fruits of dwarf elder (Sambucus ebulus L.) to a stimulated gastric fluid

New varieties of elderberry (Sambucus nigra L.). Tidsskrift for Planteavl

Processing of anthocyanin colourant from elderberry (Sambucus nigra L.) pomace. Tidsskrift for Planteavl

Sampo' and 'Samdal', elderberry cultivars for juice concentrates

Aroma composition and sensory quality of fruit juices processed from cultivars of elderberry (Sambucus nigra L.)

Interaction of vitamin C and flavonoids in elderberry (Sambucus nigra L.) during juice processing

Effect of packing materials and storage time on volatile compounds in tea processed from flowers of black elder (Sambucus nigra L.)

The relationship between sensory quality and volatile compounds in raw juice processed from elderberries (Sambucus nigra L.). European Food Research and Technology

Relationship between sensory quality and volatile compounds of elderflower (Sambucus nigra L.) extracts

Selection of elderberry (Sambucus nigra L.) genotypes best suited for the preparation of juice

Anti-Influenza virus effects of elderberry juice and its fractions

Amino-acid composition of flowers, leaves and extract of Sambucus nigra flowers

Farmakognozja. Podręcznik dla studentów farmacji. Warszawa: Wydawnictwo Lekarskie

Varieties and candidate varieties for enlarging the assortment of elderberry

Właściwości przeciwutleniające kwiatów i owoców bzu czarnego pozyskiwanego ze stanu naturalnego

Effect of traffic pollution on chemical composition of raw elderberry (Sambucus nigra L.)

Pilot clinical study on a proprietary elderberry extract: Efficacy in addressing influenza symptoms

Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses

Anthocyanins and other polyphenolics in American elderberry (Sambucus canadensis) and European elderberry (S. nigra) cultivars

Antyoksydacyjne właściwości owoców wybranych gatunków dziko rosnących drzew i krzewów

Predicting the spatial distribution of climate: Temperature in Great Britain

Antidepressant activities of Sambucuc ebulus and Sambucus nigra

Czarny bez. Zdrowie z natury czarny bez. Warszawa: Wydawnictwo RM

Demand increasing for aronia and elderberry in North America

Traditional elderflower beverages: A rich source of phenolic compounds with high antioxidant activity

Bioavailability of elderberry anthocyanins

Discovering niche markets for elderberry juice in the United States

Selection of black elderberry (Sambucus nigra L.) and evaluation of its fruits usability as biologically valuable food

Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: A randomized, doubleblind, placebo-controlled study

Detection of anthocyanins from elderberry juice in human urine

The excretion and biological antioxidant activity of elderberry antioxidants in healthy humans

Species of sambucus. Germplasm Resource Information Network (GRIN)

Classification for Kingdom Plantae Down to Family Caprifoliaceae

PLANTS database. Classification for kingdom plantae down to genus sambucus L. The United States Department of Agriculture

Zawartość metali ciężkich oraz azotanów (V) i azotanów (III) w owocach bzu czarnego i aronii czarnoowocowej w zależności od miejsca pozyskania i okresu wegetacyjnego

Gastrointestinal digested Sambucus nigra L. fruit extract protects in vitro cultured human colon cells against oxidative stress

Tannins in some anthocyanin rich fruits (in Polish). Zeszyty Naukowe Akademii Rolniczej we Wrocławiu

Rośliny lecznicze i ich praktyczne zastosowanie

Separation of flavonol-2-O-glycosides from Calendula officinalis and Sambucus nigra by high-performance liquid and micellar electrokinetic capillary chromatography

Biologicznie czynne związki polifenolowe zawarte w owocach różnych odmian hodowlanych i dziko rosnącego bzu czarnego

Fruits and vegetables in the prevention of cellular oxidative damage

Structure -antioxidant activity relationships of flavonoids and phenolic acid

Growing currants, gooseberries & elderberries in Wisconsin

Elderberry flavonoids bind to and prevent H1N1 infection in vitro

Effect of elderberry (Sambucus nigra L.) extract supplementation in STZ-induced diabetic rats fed with a high-fat diet

Über die Wirkstoffe der diaphoretischen Drogen des DAB 6

Elderberry (Sambucus nigra L.) wine: A product reach in health promoting compounds

Fractioned high pressure extraction of anthocyanins from elderberry (Sambucus nigra L

The higher the better? Differences in phenolics and cyanogenic glycosides in Sambucus nigra leaves, flowers and berries from different altitudes

Erhebung der erwerbsobstanlagen. STATISTIK AUSTRIA Bundesanstalt Statistik Österreich

Color and antioxidant properties of cyanidin-based anthocyanin pigments

Antioxidant activity of extract from elder flower (Sambucus nigra L

Ribosome-inactivating proteins

Elderberries: A source of ribosome0inactivating proteins with lectin activity

The ABC Clinical Guide to Elder Berry (2003) The American Botanical Council

A comparative evaluation of the anticancer properties of European and American elderberry fruits

Antiviral activity In vitro of Urtica dioica L., Parietaria diffusa M. et K. and Sambucus nigra L

European elderberry (Sambucus nigra L.) rich in sugars, organic acids, anthocyanins and selected polyphenols

Determination and quantification of volatile compounds in fruits of selected elderberry cultivars grown in Czech Republic

Chemical characteristics of cultivated elderberry fruit

Assessment of colour changes during storage of elderberry juice concentrate solutions using the optimization method

Impact of a proprietary concentrate of Sambucus nigra L. on urinary pH

Fruit characteristics of elderberry (Sambucus nigra L.) grown on two different soils

Yield in elderberry cultivars grown on two different soils in 1997-2003

Dziki bez czarny -pozyskiwanie surowca i jego zastosowanie

Stockley's herbal medicines interactions. A guide to the interactions of herbal medicines, dietary supplements and nutraceuticals with conventional medicines

Nowe wskazania lecznicze Sambucus nigra L. Wiadomości Zielarskie

Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections

Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries and lingonberries