Cardioprotective Effects of Cultivated Black Chokeberries (Aronia spp.): Traditional Uses, Phytochemistry and Therapeutic Effects

1. Black chokeberries: historical background, taxonomy and botanical aspects

The use of medicinal plants in the prevention and treatment of diseases is an old practice that has been maintained over time and is currently being given special attention by scientists, as well as by people aiming to preserve their health or treat a disease. In the past, the therapeutic properties of the plants were discovered by observing their effects on the animals that ate them [1, 2, 3]. People gathered knowledge about the therapeutic effects of plants and several traditional medicines were born [4]. At the beginning of the nineteenth century, the first plant compounds were isolated and later some of them served as a model for the development of synthetic drugs [4, 5]. Plant-derived products are intensively studied and they are important sources in drug discovery [1]. Studies are directed toward the identification of mechanisms of action of plant compounds [6], exploiting their capacity of reducing the side effects of synthetic drugs [7] and development of new delivery systems that can increase the efficacy of phytochemicals [8].

One of the plants whose health benefits led to numerous studies is black chokeberry, also known as black-fruited Aronia. Its fruits enjoy presently a high recognition as a health food, despite lacking the historical advantage of other well-known rosaceous berry crops (strawberries, raspberries and blackberries). The highly regarded berries (botanically: pomes), cultivated in many European countries and North America, have an unusual history, which reflects on the taxonomic confusions surrounding the plant.

Unlike other edible plants, black Aronia spread from America to Europe due to its decorative interest. The ancestor of today’s cultivated black-fruited Aronia is Aronia melanocarpa(Michx.) Elliott, a species that grows wildly in North America [9] along with two other Aroniaspecies. The small genus AroniaMedik. (chokeberry) includes multistemmed, deciduous shrubs that differ in the color and size of fruits (pomes), as well as in the pubescence of leaves, stems and inflorescences. Three North American and one European species are recognized [10]. Red chokeberry, A. arbutifolia(L.) Pers., grows up to 3 m tall and has obovate to elliptical leaves, which are shiny green on the upper side and tomentose, slightly gray on the lower side. The margins are serrated and the tip is short, acuminate. Flowers are white, in compound corymbs. In late September to early October, red fruits are produced. Black chokeberry, A. melanocarpa(Michx.) Elliott, has a smaller habit (up to 1.5 m) and is not pubescent [11]. Its fruits are black, shiny, with a diameter of 0.8–1.3 cm; they typically ripen in August. A third species native to North America, A. prunifolia(Marshall) Rehder, or purple chokeberry, is considered by certain authors to be a hybrid between the former two species, a distinct species or a variety of black or red chokeberry. It has dark purple to black fruits, and the leaf pubescence is intermediate between A. arbutifoliaand A. melanocarpa[12].

A. melanocarpais cold-hardy member of the Rosaceae family, where it is assigned to the Amygdaloideae subfamily and Maleae tribe [13]. Wild-growing black chokeberry plants were introduced to Europe in the nineteenth century as ornamental shrubs. The first record of the species in Russia (1816) mentions black Aronia under the name Mespilus melanocarpain the catalog of plants of the Kremenets Botanical Garden [14]. Soon, it was grown as a cold-resistant ornament in other botanical gardens; before the twentieth century, it was however not grown for its fruits, which, though edible, are poorly palatable and astringent. The black-fruited Aronia is cultivated nowadays as a distinct morphology in comparison to its wild-growing North American counterparts: its leaves are wider, flowers are larger and more numerous, fruits have a larger diameter, and corymbs bear a higher number of fruits [15]. It has been proposed that this species is the result of breeding and selection experiments performed in the early twentieth century by Ivan Michurin, and that all Aroniaplants cultivated in the former Soviet Union originate from the Russian pomologist’s nursery [14]. Then, it spread to other European countries such as Poland, Norway, Finland, Sweden or Germany [16]. In 1976, chokeberry was introduced to Japan [17]. The distinct differences from its wild-growing progenitors and the constancy in characteristics supported the assignment of the large-fruited chokeberry to a new species, Aronia mitschuriniiA.K.Skvortsov & Maitul [18]. Its origin is however not completely elucidated. One of the hypotheses is that the species is a hybrid obtained by backcrossing A. melanocarpawith an F1 xSorbaroniahybrid (Sorbus aucuparia× A. melanocarpa). Leonard and co-workers using amplified fragment length polymorphism (AFLP) were able to show similarities of A. mitschuriniito xSorbaroniahybrids [19]. Further studies with more sensitive and complex tools (like multilocus nuclear data) are proposed in order to firmly establish the origin of A. mitschurinii[20].

An important feature of the cultivated black-fruited Aronia is its extremely low variability due to the apomictic formation of seeds, a process occurring without fertilization of the egg. Plants resulting from apomixis are clones of the mother plant. Cultivated varieties of A. mitschurinii, including ‘Nero,’ ‘Viking’ and ‘Galicjanka,’ have in fact undistinguishable phenotypes [21] and are tetraploid (2n = 68) [14]. On the contrary, ‘Hugin’ and ‘Elata’ cultivars are considered true A. melanocarpagenotypes [21].

Taking into account the better understanding of Aroniataxonomy and genetics, in recent years, it has become accepted that the cultivated black-fruited Aronia berries, which were the subject of most biomedical and phytochemical studies, are not A. melanocarpafruits as reported. Research results should rather be assigned to A. mitschurinii, which is the only species used for commercial fruit production [21].

Further developments on the subject of black-fruited Aronia taxonomy should certainly lead to a more stable and correct nomenclature of the chokeberry species investigated by biomedical research. A unified, proper nomenclature is essential to enable researchers to assign correctly a therapeutic activity to A. melanocarpa, A. mitschurinii, or even X Sorbaronia mitschurinii,all of them used in various publications to assign cultivated black-fruited chokeberry.

2. Traditional use of black chokeberries

Although wild-growing black chokeberries (Aronia melanocarpa) were known to the North American settlers, the taste of the fruits was dissuading for a use as foodstuff. They employed fruits and bark as an astringent. The Forest Potawatomi Native Americans used the fruits of this plant in cold treatment and the preparation of traditional pemmican [17].

In Russia and Lithuania, the cultivated black chokeberry fruits were used as adjuvant treatment for high blood pressure and as anti-atherosclerotic agent [22]. Other uses include treatment of hemorrhoids, achlorhydria, avitaminosis and convalescence [17].

Because of their astringent taste, black chokeberry fruits are not usually consumed as such, but they are used for the production of juices, wines, teas, jellies or syrups, especially in fruit blends [23, 24]. Chokeberry powders are used as a natural dye in the food industry [25].

The high content of phenolic compounds, mainly anthocyanins, which are responsible for the black color of the fruits, determined an increased interest in the medicinal properties of this plant. Aroniassp. fruits have a higher antioxidant activity than other berries. Various studies emphasized antioxidant, anticancer, anti-diabetic, anti-inflammatory and hepatoprotective properties for the juice or fruit extract, which made cultivated black-fruited Aronia an important health food and dietary supplement [26].

3. Phytochemistry

Several analyses have been performed in order to evaluate the organic as well as inorganic constituents of black chokeberries. They include the research of the differences in the chemical composition of wild vs. cultivated chokeberry [21, 27], the influence of the cultivar type [28, 29, 30], the degree of fruit maturity [31], fertilization [32], the application of biosynthesis regulators [33] and geographic location [34]. Wild Aroniagenotypes contain less water and more phenolics and have a higher antioxidant activity than cultivated black chokeberries [21]. Typical values for the dry weight of cultivated black chokeberry fruits are 17.9–26%; fresh chokeberries afford 11.1–17.4% juice and 44.6–50% pomace [35]. The majority (72%) of the dry weight is constituted by dietary fiber, higher than other fruits like bilberries and currants. The study of dietary fiber with solid-state NMR could show that its components are water-insoluble fibers (cellulose, hemicellulose, lignin, cutin and pectins), soluble fibers and other constituents, which are valuable antioxidants, anthocyanins and procyanidins [36].

The sour taste of Aroniassp. berries is due to the presence of organic acids, mainly malic and citric acids. Their total content is however lower than in other berries [37]. Cultivated black chokeberries contain between 5.71 and 19.36% reducing sugars [23] and are characterized by a relatively high sorbitol amount (median content of 70 g/kg) [34] when compared to other berries. The high sorbitol content, shared as well by rowan berries (Sorbus aucuparia), may be related to the possible hybrid nature of cultivated chokeberry. Large-fruited Aronia cultivars have been hypothesized to contain the genomes of Aronia melanocarpaand Sorbus aucupariain a ratio of 3:1 [19, 21]. The high sorbitol content has been proposed to serve as an analytical tool in the control of juice blends [38]. Another feature of the sugar profile in cultivated black chokeberry is the absence of sucrose; its presence in black Aronia-based products suggests the addition of sugar or other fruits [34].

The lipid content of black cultivated chokeberries is reduced (below 0.2%) [23] and is mainly owed to hydrophobic constituents of the skin and seeds. The content in proteins is also low, with values of 10.7% in the pomace. The main amino acid was glutamic acid (19.8%), followed by aspartic acid (8.9%) and arginine (7.9%) [39].

Regarding the content in minerals, chokeberries may be valuable to complement dietary potassium and zinc intake. Among vitamins, Aronia fruits contain vitamins B1, B2, B6 and C, pantothenic acid and niacin; the detailed content has been extensively reviewed [23, 38].

The analysis of the volatile constituents in Aronia berry juice afforded the detection of 74 constituents, of which the most abundant were 3-penten-2-one, 3,9-epoxy-p-menth-1-ene and benzaldehyde. Among the aroma-active compounds, ethyl-2-methyl butanoate, ethyl-3-methyl butanoate and ethyl decanoate could account for the “fruity” aroma notes, while nonanal is responsible for the “green” notes [40]. The bitter-almond scent of the fruits is due to the presence of amygdalin [34]. This compound is a cyanogenic glycoside present in many representatives of the Rosaceae family [35]. Interestingly, a recent research aimed at identifying compounds, which inhibit adipocyte differentiation, was able to isolate from the butanol fraction of a chokeberry extract amygdalin and prunasin as active compounds [41]. These two cyanogenic glycosides suppress the expressions of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c, fatty acid synthase (FAS), and adipocyte fatty-acid–binding protein (aP2) [42].

The most intensively studied compounds in cultivated black chokeberries are phenolic compounds, mainly anthocyanins, procyanidins and phenolic acids. The total phenolic content ranges from 3440 mg/100 g dry weight to 7849 mg/100 g dry weight, depending on cultivar, ripening stage at harvest, cultivation conditions or analytical methods used for the quantification [38]. Analysis of several chokeberry cultivars identified a higher polyphenolic content for the fruits of ‘Hugin’ cultivar compared to ‘Viking,’ ‘Galicjanka’ and ‘Nero’ cultivars [29]. There are differences in the polyphenols content in chokeberry products; for example, the pomace has a five-fold higher content compared to juice [16].

Polymeric proanthocyanidins represent 66% of chokeberry polyphenols, while anthocyanins represent about 25%. The fruits contain up to 5181.60 mg/100 g dried weight polymeric procyanidins [43]. The constitutive unit is mainly (−)-epicatechin and the units are connected by C4▬C6 and C4▬C8 bonds (B-type bonds). The degree of polymerization ranges from 2 to 23 units. The main proanthocyanidins found in the fruits and bark of chokeberry are dimeric procyanidin B2 and procyanidin B5 and trimeric procyanidin C1 (Figure 1) [44].

Anthocyanins are a class of flavonoids that give blue, dark red or purple color of the fruits and they are important compounds for the biological activity of chokeberries [38]. Black chokeberries have a higher content of anthocyanins than other berries, such as blackberries, strawberries or red raspberries [45]. Anthocyanins are found mainly in fruit skin [46]. They are represented by cyanidin glycosides such as cyanidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-xyloside and cyanidin-3-arabinoside [43]. The study of the fruits of black chokeberry, ‘Viking’, ‘Nero’ and ‘Galicjanka’ cultivars revealed that ‘Nero’ and ‘Viking’ cultivars had higher anthocyanin content. Cyanidin-3-galactoside and cyanidin-3-arabinoside are the major anthocyanins in chokeberries, while cyanidin-3-xyloside and cyanidin-3-glucoside are found in lower amounts [47]. The fruits also contain pelargonidin-3-arabinoside and pelargonidin-3-galactoside in trace amounts [17, 38]. Other anthocyanins such as cyanidin-3-pentoside-(epi)catechin, cyanidin-3,5-hexoside-(epi)catechin, and cyanidin-3-hexoside-(epi)cat-(epi)cat were identified in black chokeberry juice and powder [46].

The main phenolic acids in black chokeberries are chlorogenic and neochlorogenic acids. They represent about 7.5% of fruit polyphenols [43]. In addition to chlorogenic and neochlorogenic acids, other phenolic acids such as cryptochlorogenic acid, 3-O-p-coumaroylquinic acid and di-caffeic quinic acid have been reported in chokeberries [46]. Chokeberry juice contains a greater amount of these compounds than pomace [43]. Fruits of ‘Viking’ cultivar and wild chokeberry have a higher content of phenolic acids compared to fruits of ‘Nero’ and ‘Galicjanka’ cultivars [47].

Chokeberry also contains flavonol glycosides such as quercetin 3-O-galactoside, quercetin 3-O-rutinoside, quercetin 3-O-glucoside, quercetin 3-O-arabinoside, isorhamnetin 3-O-rutinoside or kaempferol 3-O-glucoside [48]. Other phenolic compounds identified in chokeberry fruits and flowers are the flavanone eriodictyol-7-O-β-glucuronide and the flavonols quercetin-3-robinobioside and quercetin-3-vicianoside [49]. Even though the fruits were the most investigated for the polyphenols in their composition, black chokeberry leaves also contain these compounds, with a higher content in the young leaves compared to the old ones (Figure 1) [50].

4. Cardioprotective actions: in vivoand in vitrostudies: clinical trials

Diseases of the circulatory system were reported to be the main cause of death in Europe and America [51, 52]. The affections of the circulatory system are related to high blood pressure, smoking, cholesterol and diabetes (the main pathologies of modern times), resulting in stroke or ischemic heart disease as the major pathologies causing invalidity and death in the developed countries [53].

Obesity, sedentary lifestyle, diet, smoking and stress are the principal inducers of endothelial dysfunction and insulin resistance, which will later induce hypertension and diabetes [54]. Thus, targeting endothelial dysfunction, insulin resistance and the altered metabolic state represents important strategies for decreasing the incidence and complications of cardiovascular diseases, as well as the medical costs [53, 55].

As well known, the vascular endothelium is the single layer of cells that lines the internal lumen of blood vessels [54, 56]. A healthy endothelium is essential for the cardiovascular system and is considered nowadays an organ [53, 57]. It possesses several important functions such as relaxation of vascular smooth muscle cells, inhibition of platelet aggregation, limitation of leukocyte adhesion, regulation of the vascular tone, inhibition of vascular smooth proliferation, and specialized autocrine and paracrine secretion (producing and secreting vasoactive, vasoprotective, angiogenic, inflammatory and thrombotic/antithrombotic molecules) [53, 55, 57]. It also produces growth factors and responds to physical and chemical signals. The term “endothelial dysfunction” is used not only to describe the impaired metabolism of nitric oxide (NO) or the imbalance of endothelium-derived relaxing and constrictor factors, but also to describe an aberrant endothelium activation and abnormalities between endothelium and leukocytes, platelets and other regulatory molecules [53, 58, 59]. Thus, it plays an essential role in the pathogenesis of several cardiovascular (hypertension, atherosclerosis, systemic and pulmonary hypertension, etc.), as well as other diseases (inflammatory diseases or cancer) (Figure 2) [60, 61, 62].

Elevated oxidative stress is another major risk factor of cardiovascular pathologies as an altered metabolic state will increase the reactive oxygen species (ROS) production, which will determine an increase in lipid peroxidation, inflammation, endothelial dysfunction, platelet aggregation and activation [63]. On endothelial cells, oxidative stress has been shown to immediately increase vessel damage. Moreover, the lesion caused by oxidative stress can affect the entire body’s organs and systems (Figure 2) [64].

Thus, it is important to find new therapeutic strategies to improve endothelial function and decrease ROS as strategies for the primary prevention of cardiovascular diseases in the ever-aging Western societies.

In the last decade, several plant bioactive substances (called nutraceuticals) have proven to have outstanding properties, which suggest that they could play an important role in preventing the onset and development of chronic diseases. The term nutraceutical refers to a natural bioactive compound with several properties, such as health promoting, disease preventing or medicinal properties [65].

Cultivated black chokeberry fruits have been discovered to contain an enormous source of bioactive compounds such as antioxidants‑especially polyphenols, flavonoids (anthocyanins, flavonols and flavanols), vitamins (C and E), minerals (potassium, magnesium and calcium), pectins, carotenoids and carbohydrates [16]. Moreover, the in vitroand in vivostudies have highlighted its antioxidant (one of the richest plants in antioxidants), anti-inflammatory, anti-proliferative, anti-atherosclerotic, hypotensive, antiplatelet, gastroprotective, antimicrobial (antibacterial and antiviral), immunomodulatory and anti-tumor profile, making it an excellent candidate for the prevention of cardiovascular and metabolic disorders [16, 66].

Herein, the main and the latest findings regarding the cardioprotective properties of cultivated black chokeberry will be presented and discussed (Figure 3).

5. Conclusions and perspectives

From all the information presented above, one can conclude that black chokeberry is an extremely rich source of bioactive molecules that are offering an excellent cardioprotection among other fruits and that can be used in both primary and secondary prevention of cardiovascular events. Despite the low bioavailability of polyphenols and their variability, they are exceptionally important for their health-promoting properties. Based on the present findings, it can be definitely included in a healthy daily diet. However, much more research is needed to completely understand the exact mechanisms as well as the full-length actions of black chokeberry, especially in humans. Complete bioavailability studies are required concerning Aronia bioactive molecules. Moreover, the investigation of the risk of tissue accumulation, as well as appreciation of the risk/benefit ratio in humans, will be extremely beneficial. The recommended daily intake should also be established.

Conflict of interest

“The authors declare no conflict of interest.”