Bioactive Compounds, Antioxidant Activities, and Health Beneficial Effects of Selected Commercial Berry Fruits: A Review

Epidemiological studies have provided the evidence that regular consumption of fruits and vegetables reduce the risk of pathological condition such as cardiovascular disease, cancer, inflammation, and aging. Among fruits, berries are considered as superfruits due to their highly packed phytochemicals comprising phenolic acids, flavonoids viz. flavonols, flavanols, and anthocyanins. These bioactive compounds are associated with significant antioxidant, antidiabetic, antiinflammation, and anticancer properties. This review highlights the basic information and interesting findings of some selected commercial berries with their phytochemical composition, antioxidant properties, and potential health benefits to human.


Source
Historically, blueberries have been a popular fruit due to their well-known health and nutritional benefits. Blueberries belongs to family Ericacea and genus Vaccinum. Numerous species (approx. 450) of blueberries are grown wildly or cultivated worldwide. Major commercially available blue berries that are grown across the worldwide are rabbit eye blueberries (Vaccinium ashei), lowbush blueberry (Vaccinium angustifolium A.) and highbush blueberry (Vaccinium corymbosum L.). USA is the largest producer of blue berries in world after Australia and Canada. However various part of the Europe and other countries produce blueberries commercially. Blueberries are highly perishable and therefore blueberries are processed after harvesting. Various postharvest techniques for storage and processing are applied to prolong their shelf lives and preserve quality properties of blueberry.

Composition
Blueberries are packed with various nutrients and bioactive active compounds. They are listed top of the superfoods. Blueberries are the richest source of polyphenolic compounds. It also contains several vitamins including vitamin C. Numerous studies have been carried out to screen the level polyphenolic compounds including analysis by chromatographic and mass spectrophotometric analysis. Analysis in the content of total phenolic compounds and total anthocyanins demonstrated that it has several folds differences among the different varieties depending on the geographic location and agricultural practices. Major polyphenolic compounds of blueberries are flavonols (mainly quercetin derivatives), anthocyanins, flavan-3-ols, proanthocyanidins, and phenolic acids (Table 1). Among the phenolic acids of blueberries hydroxycinnamic and hydroxybenzoic acids and their derivatives such as chlorogenic, caffeic, gallic, p-coumaric, ferulic, ellagic, syringic, vanillic acids are common (Kalt & McDonald, 1996;Kalt, Forney, Martin, & Prior, 1999, Gu et al., 2004Rodriguez-Mateos, Cifuentes-Gomez, Tabatabaee, Lecras, Spencer, 2012,;). Anthocyanins are the major polyphenolic compounds comprising 60% of total phenolic compounds in blue berries. In a study of 215 phenotypes of blueberries cyanidin-3-glucoside was reported to be the major again among the anthocyanin compounds (Kalt, et al., 2001). In some other studies it was found that malvidin, delphinidin, petunidin, and peonidin are the major components comprising 75% of all identified anthocyanins (Scibisz & Mitek, 2007;Routray & Orsat, 2011).The composition and levels of anthocyanins in blueberries vary with cultivars and varieties. The color of blueberries also varies with the composition of anthocyanins (Routray & Orsat, 2011). The level of polyphenolic compounds differs with maturity stages of blueberries where ripening stages showed higher level of anthocyanins than the other phenolic compounds. Postharvest condition such as oxygen level, temperature, and light of blueberries impacts the nutritional quality and phenolic contents (Kalt, Forney, Martin, & Prior, 1999).

Health Benefits
Blueberries have tremendous pharmacological properties. Consumption of blueberries help in controlling diabetes and its complication such as lowering blood pressure and blood cholesterol Basu, et al.,2010;Stull, Cash, Johnson, Champagne, & Cefalu, 2010, McAnulty, Collier, Pike, Thompson, & McAnulty, 2019. It possesses anti-diabetic properties and help to protect pancreatic β-cells from glucose-induced oxidative stress (Al-Awwadi, et al., 2005;. It has been reported that consumption of blueberry significantly reduced H 2 O 2 -induced DNA damage (Del Bo′, et al., 2013). Phytochemicals present in blueberry could inhibit the growth and metastatic potential of breast and colon cancer cells (Adams, Phung, Yee, Seeram, Li, & Chen, 2010;Schantz, 2010). It was found that pure anthocyanins, such as cyanidin, delphinidin, as well as peonidin 3-glucoside, suppressed growth of human tumor cells and apoptosis of colon and breast cell line. In a recent clinical study comprising 52 US adult veterans reported that consumption of 22 g freeze-dried blueberries for 8 weeks could beneficially affect cardiometabolic health parameters in men with type 2 diabetes (Stote, et al., 2020). Recently Rodriguez-Daza et al., (2020) revealed the key role of blueberry extract with proanthocynaidins in modulating the gut microbiota and restoring colonic epithelial mucus layer triggering health effects of blueberry polyphenols (Rodriguez-Daza et al., 2020). Moreover Türck, et al., (2020) evaluated the effect of blueberry extract on functional parameters and oxidative stress levels in rat lungs with pulmonary arterial hypertension (PAH) and reported that intervention with blueberry extract mitigated functional PAH outcomes through improvement of the pulmonary redox state (Türck et al., 2020). Tian et al., (2019) reported that cyanidin-3-arabinoside extracted from blueberry as a selective Protein Tyrosine Phosphatase 1B Inhibitor (PTP1B) which is an important target for type 2 diabetes (Tian et al., 2019). PTP1B inhibitors can reduce blood glucose levels by increasing insulin sensitivity. Jielong et al., (2019) reported that extracts of blueberry reduces obesity complications through the regulation of gut microbiota and bile acids via pathways involving FXR(Farensoid X Receptor) and TGR5 (Jielong, Xue, Hongyu, Weidong, Yilin, & Jicheng, 2019).

Source
Bilberry (Vaccinium myrtillus L.) a small dark blue berry belongs to Ericacea family and is native to Europe and North America. Bilberry is also known as European blueberry differs from blueberry relative to Vaccinium corymbosum and Vaccinium angustifolium with their morphology and flesh color. The blue coloration is due to its high content in anthocyanin (Prior et al., 1998). Cultivation of bilberries have been increasing continuously during several years.

Source
Cranberries (Vaccinium macrocarpon Ait.) also known as lowbush cranberries are native to USA belongs to Ericaceae family. USA is the world leader of cranberry producer with 90% of world production. Cranberries are consumed as fresh fruits, dried, jams, and juices. The US per capita consumption of cranberries is raising continuously mostly in the form of juices and remains at the top of healthy drinks.

Composition
Cranberries are rich source of various phytochemical compounds viz., flavan-3-ols, A type procyanidins (PACs), anthocyanins, benzoic acid, ursolic acid, and vitamin C (Table1). Among the PAC's comprising catechin, epicatchin, epigallocatechin cranberries have been known to have epicatechin as the major one. Although many fruits have proanthocyanidins but only cranberry have significant level of A type PAC. Recently Wang et al., (2020) investigated the analysis of cranberry proanthocyanidins using UPLC (Ultra Performance-ion mobility-high-resolution mass spectrometry and identified total of 304 individual A-type and B-type proanthocyanidins, including 40 trimers, 68 tetramers, 53 pentamers, 54 hexamers, 49 heptamers, 28 octamers, and 12 nonamers (Wang, Harrington, Chang, Wu, & Chen, 2020). Anthocyanins in cranberries are composed of glycosides of the 6 aglycones with cyanidin, peonidin, malvidin, pelargonidin, delphinidin, and petunidin (Wu, & Prior, 2005). The major phenolic acid including hydroxycinnamic acids in cranberry are p-coumaric, sinapic, caffeic, and ferulic acids. Quercetin is the major flavonol compound present in cranberries. Ellagic acid with and without glucosides represent more than 50% of total phenolic compounds. However, level of phenolics and anthocyanins depends on the maturation stage of the cranberries.

Health Benefits
Cranberries have been used for several decades to prevent urinary tract infection. This health benefit is attributed to cranberries because proanthocyanidin can prevent adhering of Escherichia coli to uroepithelial cells in the urinary tract (Ermel, Georgeault, Inisan, Besnard, 2012). After consumption juice and various products of cranberries it was also believed to enhance the plasma antioxidant activities (Pedersen et al., 2000). In vitro study confirmed that cranberry extracts inhibited activities of angiotensin converting enzyme and thus it showed the potential in lowering blood pressure (Apostolidis, Kwon, & Shetty, 2006). Cranberry also helped to reduce the cardiovascular disease risks and to protect against lipoprotein oxidation. Several studies confirmed that cranberries bioactive compounds have anti-cancer and antimutagenic activities (Prasain, Grubbs, & Barnes, 2020;Howell, 2020). Recently Hsia et al., (2020) investigated that whether consumption of cranberry beverage would improve insulin sensitivity and other cardiovascular complications and reported that daily consumption for 8 weeks may not impact insulin sensitivity but could be helpful in lowering triglycerides and alters some oxidative stress biomarkers in obese individuals with a proinflammatory state (Hsia, Zhang, Beyl, Greenway, & Khoo, 2020). Chew et al., (2019) reported the health benefits of cranberry beverage consumption on gluco regulation, oxidative damage, inflammation, and lipid metabolism in healthy overweight humans (Chew et al., 2019). Consumption of significant amount of cranberry beverage improved antioxidant status and reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Source
Viburnum opulus L. (Adoxaceae), commonly known as European guelder, is also called as European cranberry bush, guelder rose, cherry-wood, and snowball bush. It grows in Europe, North and Central Asia, and North Africa. Viburnum is commonly used both in conventional and folk medicine in Russia. The State Pharmacopoeia of the Russian Federation (XI edition, issue 2) contains a monograph on the preparation of Viburnum fruits, and two medicinal drugs with Viburnum fruits are entered in the State Register of Medicinal Remedies of the Russian Federation. While parts of viburnum such as bark, flowers, and fruits are widely used in traditional medicine some fruits are used as cooking ingredients. In Russia, Ukraine, and among many Siberian nations the viburnum opulus (VO) fruits are used in traditional cuisine such as marmalades, jams, and "Kalinnikov" pies, and herbal teas.

Cherries 2.6.1 Source
Cherry is one of the major small fruits with bigger benefits belongs to family: Rosaceae and genus: Prunus. It is one of the major berries native to United States and is the second-largest producer in the world. The two major types of cherries are sweet cherries (Prunus avium) and tart or sour cherries (Prunus cerasus).

Health Benefits
Various studies demonstrated that tart cherries extract, and its compounds showed strong antioxidant activities (Blando, Gerardi, & Nicoletti, 2004). Kirakosyan et al., (2008) reported the high TEAC (trolox equivalent antioxidant capacity) of two tart cherries viz Balaton and Montmorency and cyanidin and its derivatives were found to be the important antioxidants in the assays (Kirakosyan, Seymour, Llanes, Daniel, Kaufman, & Bolling, 2008). Numerous studies indicated that cherry consumption inhibited inflammatory pathways. Consumption of cherries also helped to lower blood pressure, control blood glucose, protect against oxidative stress, and reduce inflammation (Martin, Burrel, & Bopp, 2018;Martin, & Coles, 2019). Kelley et al. (2006) showed that intake of sweet cherries decreased levels of C-reactive protein (CRP), a biomarker for inflammation and cardiovascular disease in healthy subjects (Kelley, Rasooly, Jacob, Kader, Mackey, 2006). In vitro and in vivo studies suggested that anti-inflammatory properties of polyphenolic compounds of cherries evidenced by the inhibition of activity of the cyclooxygenase II (COX II), another biomarkers for inflammation, carcinogenesis, cell proliferation, and angiogenesis (Wang, Nair, & Strasburg,1999). Consumption of Cherry also showed to lower serum urate levels and inflammation (Martin, & Coles, 2019). Zhang et al., (2012). reported that cherry consumption affected the risk of recurrent gout attacks (Zhang, Neogi, Chen, Chaisson, Hunter, & Choi, 2012). Recently Lamb et al., (2020) also demonstrated the effect of tart cherry juice to reduce risk of recurrent gout flare (Lamb, Lynn, Russell, & Barker, 2020). Di Bonaventura et al., (2020) indicated that tract cherry has potential role to prevent obesity-related risk factors, especially neuroinflammation based on a rat model study (Di Bonaventura et al., 2020). In a mice model study Smith et al., (2019) found that cherry supplementation (5% and 10%) improved bone mineral density (BMD) and some indices of trabecular and cortical bone microarchitecture and they proposed that these effects were likely attributed to increased bone mineralization (Smith et al., 2019).

Source
Sea buckthorn, known as seaberry, (Elaeagnus rhamnoides L.) belongs to the family Elaeagnaceae. Even though sebuckthorn is cultivated mostly in Russia and China, now a days it is cultivated around other countries like Finland, Germany, and Estonia.

Health Benefits
Sea buckthorn exhibits a wide spectrum of pharmacological activities such as anti-inflammatory, anticancer, antioxidant, and anti-atherosclerotic activities (Zeb, 2006;Basu, Prasad, Jayamurthy, Pal, Arumughan, & Sawhney, 2007;Olas, 2016). They also induce apoptosis and strengthen the immune system. In a study on the content and antioxidant activities of phenolic compounds of seabucthorn Gao et al., (2000) reported that antioxidant activities were strongly correlated with the content of total phenolic compounds and ascorbic acid (Gao, Ohlander, Jeppsson, Bjork, & Trajkovski, 2000). It was also found that antioxidant activity of the lipophilic extract correlated with the total carotenoids content. A strong correlation existed between flavonoid content in seabuckthorn and their antioxidant activities (r = 0.96) (Criste et al., 2020). To investigate other health benefits recently Guo et al., (2020) reported that administration of freeze-dried seabuckthorn powder lowered body weight, Lee's index, adipose tissue weight, liver weight, and serum lipid levels induced by obesity (Guo, Han, Li, & Yu, 2020). Tkacz et al., (2019) reported high in-vitro anti-oxidant and anti-enzymatic activities related to digestion system due to the presence of phytochemicals such as phenolic acids, flavonols, xanthophylls, carotenes, tocopherols, and tocotrienols ( Tkacz, Wojdyło, Turkiewicz, Bobak, & Nowicka, 2019). Number of studies reported that seabuckthorn oil exhibits anti-tumor properties due to the presence flavonoid compounds kaempferol, quercetin, and isorhamnetin (Christaki, 2012). Hao et al., (2019) found that seabuckthorn seed oil extracts were effective in reducing blood cholesterol in hypercholesterolemia hamsters (Hao et al., 2019).

Source
Raspberries, a popular soft fruit grown in Eastern Europe belongs to the family Rosaceae and genus Rubus. It is cultivated all over the world mainly in Europe (European red raspberry), North America (American variety), and Asia. In the early of 19 th century raspberries were grown in the United State of America. Now it is the third highest producer of raspberries. Black raspberries are also grown commercially in America. Purple raspberries are the hybrid of red and black raspberries. There are approximately 250 species of Rubus genera fruits however red raspberry (Rubus idaeus L.), the North American red raspberry (R. idaeus), and the black raspberry (Rubus occidentalis L.) are the most important commercial varieties .

Health Benefits
Raspberries confers significant antioxidant activities because of their polyphenolic compounds. (Lee, Dossett, & Finn, 2012;Chen, Xin, Zhang, & Yuan, 2013). Raspberries have been known to use traditional drug such as antipyretic and diaphoretic drug. It has been used in managing diabetes and hypertension, and inflammation (Liu,Schwimer, Liu, Greenway,Anthony, & Woltering, 2005;Cheplick, Kwon, Bhowmik, & Shetty, 2007;Medda et al., 2015 ). Polyphenol compounds of raspberries exerted antiproliferative activities against cervical and colon cancer cells (McDougall, Ross, Ikeji, & Stewart, 2008). The raspberries extract also showed anti-proliferative activities against colon, prostate, breast, and oral cancer cells. (Wedge et al., 2001;Seeram et al., 2006;Ross, McDougall, & Steward, 2007;Peiffer, 2018). Raspberry phenolics exhibited antimicrobial and antiviral activities. A growing evidence was found that berries could modify the composition of the gut microbiota (May, McDermott, Marchesi & Perry, 2020). Recently Tu et al., (2020) investigated that administration of a diet rich in black raspberry changed the composition and diverse functional pathways in the mouse gut microbiome which suggested important role of the gut microbiome in the health effects of black raspberry extract (Tu et al., 2020).

Source
Aç aí a palm fruit, belongs to family Arecaceae and genus Euterpe. They are native to South America and grows significantly in the Amazon River delta in Brazil. Two primary species of aç aí fruit that are popular are Euterpe precatoria (EP) and Euterpe oleracea (EO).They are highly consumed by the native people in that region but it has gained international reputation because of their potential nutrition and health benefits. The use of aca̧ı́ berries by native people to treat malaria related symptoms such as fever, pain, inflammation, and anemia has been seen long time. In the US marketplace commercial products containing aç ai fruit have been increasing rapidly during recent years (Lee, 2019).

Health Benefits
Due to the presence of various polyphenolic composition, aca̧ı́ berries exhibit important health benefits. Various cell and animal model studies indicated that aç aí extracts showed antioxidant, anti-inflammatory, anti-atherosclerotic, anti-aging, analgesic, and neuromodulatory properties.
Through antioxidant and anti-inflammatory activities acai berry extracts reduced the risk of atherosclerosis (Mertens-Talcott et al., 2008). Moreover, Xie et al. (2012) proposed that anti-inflammatory activities were attributed to the flavone velutin (Xie, et al., 2012). In-vivo and in-vitro cell and animal model study confirmed that extracts of acai fruits reduce oxidative stress and neuroinflammation via inhibition of activities and expression of nitrous oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (p38-MAPK), tumor necrosis factor-α (TNF-α), and nuclear factor κB (NF-κB) (Poulose et al., 2012). Extract of aç aí fruit pulp specially from EO protected from neurotoxicity induced by lipopolysaccharide in mouse brain (Noratto, Angel-morales, Talcott, & Mertenstalcott, 2011;Poulose et al., 2012). In addition to the in vivo and in vitro antioxidant and anticancer activities it was reported that Aç aí juice from EO exhibited neuroprotective, anticonvulsant, and anti-seizure properties (Souza-Monteiro et al., 2015). Ferriera, et al., (2019) investigated potential use of aca̧ı́ polyphenols as novel antimalarial compounds in vitro and in vivo and indicated its potential effects of proteostasis as major molecular target (Ferriera, et al., 2019). Magalhã es et al., (2020) demonstrated the protective effect of aç aí pulp components on intestinal damage in 5-fluorouracil-induced Mucositis, as well as the ability to control the response to oxidative stress, in order to mobilize defense pathways and promote tissue repair (Magalhã es et al., 2020). Recently de Liz et al., (2020) evaluated the effects of moderate-term aç aí juice intake on fasting glucose, lipid profile, and oxidative stress biomarkers in healthy subject by assigning 200 mL/day for four weeks and collected blood before and after consumption. They found that there were increased the concentrations of HDLC (high-density lipoprotein cholesterol) by 7.7%, TAC (total antioxidant capacity) by 66.7%, antioxidant enzyme activities catalase by 275.1%, and glutatathone peroxidase activity by 15.3% (de Liz et al., 2020).

Source
Maqui berry (Aristotelia chilensis), belongs to the family Elaeocarpaceae. This purple berry is native to Chile (Aristotelia chilensis) is one of the emerging Chilean superfruit with high nutraceutical value. It is consumed as fresh and dried fruits or also used to make tea, jam, cakes, drink, juice, alcoholic beverages.

Health Benefits
Maqui berry is reported to exhibit high antioxidant activities. The ORAC values of maqui was found to be 37,174 µmol Trolox per 100 g of dry weight which was much higher than in commercial berries such as raspberries, blueberries and blackberries cultivated in Chile (Speisky, López Alarcón, Gómez, Fuentes, & Sandoval Acuña, 2012). Bastí as-Montes (2020) et al., also recently showed that seed oil from Maqui berry and their tocols (α, β, γ, δ-tocopherols, tocotrienols, and β-sitosterol) promoted for clinical investigation due to their high antioxidative and antiobesity potential against DPPH, HORAC (Hydroxyl Radical Antioxidant Capacity), ORAC (Oxygen Radical Absorbance Capacity), FRAP (ferric reducing antioxidant power), Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase (Bastí as-Montes et al., 2020). The purified delphinidin extract maqui berry helped in the generation of nitrogen oxide (NO) in endothelial cells, decreased platelet adhesion, and possessed anti-inflammatory effects. Miranda-Rottmann, et al., (2002) reported that maqui berry extracts could prevent the oxidation of low-density lipoproteins and protected the cultures of human endothelial cells (Miranda-Rottmann, Aspillaga, Pé rez, Vasquez, Martinez, & Leighton, 2002). Maqui berries are used as dietary management in patients with respiratory disorders as anthocyanin maqui extract could normalize H 2 O 2 and IL-6 concentrations in exhaled breath condensates (EBC) by asymptomatic smokers (Vergara, Ávila, Escobar, Carrasco-Pozo,, Sá nchez, & Gotteland,2015). Recently Zhou et al., (2019) reported that ethyl acetate fraction from maqui berry crude extract was rich in phenols and exhibited strong antioxidant and anti-inflammatory activities. They suggested that there was a possible prevention of cognitive damage due to the antioxidant activity of the maqui berry (Zhou et al., 2019). In a study with male rat brain exposed to ozone and treatment with extract of Maqui berry it was found that maqui berry extracts improved memory and decreased oxidative stress (Bribiesca-Cruz, Moreno, Garcí a-Viguera, Gallardo, Segura-Uribe, Pinto-Almazá n, & Guerra-Araiza, 2019).

Elderberries
2.11.1 Source Elderberry (Sambucus nigra) is one of the richest sources of anthocyanins and are used as great source for production of antioxidants, colorants, and bioactive compounds industrially. Traditionally they have been used as medicinal components and food ingredients in fruits, jams, and juices. They are also more frequently used in the manufacture of various types of liqueurs.

Health benefits
Elderberry has been used as folk medicine for the treatment of common cold, fevers, allergies, and ailments. Several reports demonstrated that elderberries are associated with antioxidant, anti-inflammatory, antibacterial, antiviral, and inflammation properties and various health beneficial properties (Sidor & Gramza-Michałowska, 2015;Porter & Bode, 2017;Olejnik, et al., 2015). Antioxidant activities of elderberries and its extracts were confirmed by in vitro antiradical activity assays viz., DPPH, ABTS, hydroxyl, and peroxyl. However, the potency of antioxidant activities depended on the assay, method of extraction bioactive compounds as well as type of elderberry cultivars. In some studies, it showed a less activities than choke berries and black berries and whereas in some other studies it showed higher than other berries (Viskelis, Rubinskiene˙, Bobinaite˙, & Dambrauskiene, 2010;Wu et al. (2004)). Wu et al. (2004) investigated ability of elderberry extract to scavenge the peroxyl radical (ROO•) in the ORAC assay and reported upto 5783 µmol TE/g extract which was higher than the activity of other extract of berries in the respective assay (Wu, Gu, Prior, & McKay,2004). In vivo studies showed that an enhanced plasma and serum antioxidant activity was observed after consumption of elderberry (Netzel et al. (2005).
Several studies indicated the antidiabetic properties of elderberry extract. Administration of elderberry extract to diabetic rats helped to maintain glycemic index and reduced the increase in glycemia (Badescu, Badulescu, Badescu, & Ciocoiu, 2012). Bhattacharya et al., (2013) reported the possible role of elderberry in the prevention and treatment of diabetes via the increasing in the secretion of insulin (Bhattacharya et al., 2013). Ho et al., (2017 a, b) reported that elderberry extracts showed high stimulation of glucose uptake in human liver cells and human skeletal muscle cells and inhibitory effect towards carbohydrate hydrolyzing enzymes after treatment with elderberry extracts (Ho, Nguyen, Kase,Tadesse, Barsett, & Wangensteen, 2017). In vivo studies with STZ-induced diabetic rat fed with high fat diet Salvador et al., (2017) found that polar extract of elderberry modulated glucose metabolism by correcting hyperglycemia and in other way the lipophilic extract lowered insulin secretion (Salvador et al., 2017). Elderberry extract reported to boost immune system (Badescu, Badulescu, Badescu, Ciocoiu, 2015). Anti-inflammatory properties by elderberry extracts were evident from the findings that elderberry stimulated the production of proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α (tumour necrosis factor) as well as anti-inflammatory cytokine IL-10 ( Barak, Birkenfeld, Halperin, & Kalickman, 2002). Several studies indicated elderberry extract for antimicrobial and antiviral activity against human pathogenic bacteria as well as influenza viruses (Krawitz, Mraheil, Stein, Imirzalioglu, Domann, Pleschka, &Hain, 2011). Elderberry flower extract inhibited the influenza A virus (H1N1)-induced Madin-Darby canine kidney (MDCK) cell infection (Roschek, Fink, McMichael, Li, & Alberte, 2009). Recently it was reported that Sambucus Formosana Nakai stem ethanol extract displayed strong anti-HCoV-NL63 related to respiratory tract illnesses including runny nose, cough, bronchiolitis, and pneumonia (Weng et al. 2019). A significant study demonstrated the anticancer properties of elderberries including European and American elderberry fruits which demonstrated chemopreventive potential through strong induction of quinone reductase and inhibition of cyclooxygenase-2 (Thole et al, 2007).

Conclusion
A wide spectrum of in vitro and in vivo, and human studies has proven the berries antioxidant status and potential health benefits including cardiovascular, neuroprotective, anticarcinogenic potential, and antidiabetic properties. However, the bioavailability of polyphenolic compounds appears to be different with their structure, composition, and diet sources. Abundancy of polyphenols may not correlate strongly with the bioavailability. A thorough knowledge of the bioavailability of the series of polyphenolic compounds will help in promoting healthy choices for maximum health benefits. Further studies in profiling bioavailability and medicinal value are needed for potential application.