What Are the Active Ingredients in Blueberry Extract?

Blueberries are plants in the genus Vaccinium of the family Ericaceae. Blueberry fruits are rich in various functional ingredients, mainly polyphenols. Their health benefits involve antioxidant, cardiovascular protection, assisting in lowering blood lipids, enhancing memory, boosting immunity, anti-tumor and relieving visual fatigue, etc.[1-6]. They are one of the five major healthy fruits recommended by the FAO. This article aims to systematically review the main functional components, health benefits and current development and utilization status of blueberries, with the aim of providing a reference for the in-depth development and utilization of blueberries.

1 Active Ingredients of blueberries

1.1 Anthocyanins

Anthocyanins contained in blueberries are a kind of water-soluble flavonoid pigment that is widely found in plants. Anthocyanins have unpaired electrons in their molecular structure, which can supply electrons and hydrogen to free radicals, thus effectively terminating active oxygen free radicals in the body. The antioxidant capacity of anthocyanins is 50 times that of VE and 200 times that of VC [7], and they are one of the natural plant ingredients with the best antioxidant effect discovered so far.

Ye Hongling et al. [8] used ultrasound to extract anthocyanins from blueberry pomace and analyzed them to obtain five anthocyanins, namely, malvidin, cyanidin, delphinidin, petunidin and peonidin. The color of the blueberry peel is determined by the ratio and content of anthocyanin compounds. Tian Mixia et al. [9] analyzed the anthocyanin content of 60 blueberry varieties collected in Jilin and found that the average anthocyanin content of fresh blueberries was as high as 5.378 mg/g. Anthocyanins are considered to be the main substance basis for the antioxidant, vision protection, anti-cancer, anti-radiation, anti-aging, and immunity-enhancing effects of blueberries [10-11]. The development of new blueberry functional products meets the current huge market demand for health products such as anti-aging, anti-tumor and beauty products, and the control of technological losses of blueberry anthocyanins has also become a core concern in the processing of blueberries.

1.2 Phenolic acids

Phenolic acids are a class of organic acids with a phenolic ring in their structure, mostly derivatives of hydroxybenzoic acid and p-hydroxycinnamic acid. Phenolic acids are one of the main functional ingredients in blueberries. They have strong antioxidant properties, can effectively remove free radicals in human cells, and reduce oxidative damage. Phenolic acids also have antibacterial, cardiovascular disease prevention, blood pressure lowering, and central nervous system stimulation functions. Natural phenolic substances are currently a research hotspot in the fields of nutrition, medicine, and food science, and are widely used in health foods, cosmetics, pharmaceuticals, and other fields [12-13]. Blueberries are rich in phenolic acids and provide the basis for their various health benefits. Liu Yixiang et al. [14] found that wild blueberries from the Greater Khingan Mountains contain more than 11 phenolic acids, and identified 7 phenolic acids: chlorogenic acid, gallic acid, caffeic acid, cinnamic acid, ferulic acid, protocatechuic acid and p-coumaric acid. Mattila et al. [15] determined the phenolic acid content in blueberries to be 85 mg/100 g using HPLC.

1.3 Ursolic acid

Ursolic acid, also known as ursoic acid and ursolic acid, is a pentacyclic triterpenoid compound that exists in plants as a free aglycone or glycoside. Ursolic acid has a variety of biological effects such as antibacterial, antidiabetic, hepatoprotective and other biological effects and antioxidant effects, and has been widely used in clinical practice. Geon-Hee et al. [1 6] showed that ursolic acid can inhibit the growth of liver cancer cells by lowering cholesterol, and can be used for the prevention and treatment of liver cancer and chronic diseases related to cholesterol. Meng Yanqiu et al. [17] used the MTT method to study the in vitro antitumor effect of ursolic acid and found that ursolic acid has a certain degree of inhibitory effect on the proliferation of HeLa, HepG2 and BGC-823 cells, and the activity is significantly higher than that of the marketed drug gefitinib.

Ursolic acid can also improve type 2 diabetes by increasing the transport and expression of the GLUT4 protein in mouse muscle cells[18]; it has a significant stabilizing and cooling effect on the central nervous system, can significantly reduce mouse body temperature and reduce mouse activity[19]. A study[20] measured the ursolic acid content of dried blueberries to be 11. 8 mg/100 g. Based on the free radical theory of antitumor, the antioxidant effect of blueberry polyphenols can work synergistically with blueberry ursolic acid to exert an antitumor effect.

1.4 Chlorogenic acid

Chlorogenic acid is a condensed phenolic acid composed of caffeic acid and quinic acid, also known as coffee tannic acid. Chlorogenic acid is widely found in plants such as honeysuckle, sunflower, blueberry, and coffee. It is a phenylpropanoid compound produced during aerobic respiration of plants through the shikimic acid biosynthesis pathway. It is the main active ingredient in many Chinese herbal medicines for anti-inflammatory, heat-clearing and detoxification purposes[21].

Long Yan et al. [22] used HPLC to determine the chlorogenic acid content in blueberry fruit to be 0.69 mg/g, and the chlorogenic acid content in blueberry leaves was significantly higher than that in the fruit [23]. Pharmacological tests have shown that chlorogenic acid has various physiological activities such as antioxidant, anti-inflammatory, hepatoprotective, anticoagulant and antitumor activities [24]; chlorogenic acid can chelate with aluminum ions, and its antioxidant effect can reduce the cytotoxicity of aluminum chloride on PC12 cells [25]. Therefore, eating foods rich in chlorogenic acid can reduce the damage of aluminum to the nervous system.

1.5 Ellagic acid

Ellagic acid is a kind of polyphenol di-lactone, a dimer derivative of gallic acid, which is widely found in various soft fruits, nuts and other plant tissues in the form of free or condensed forms. It has various biological effects such as anti-oxidation, inhibition of cancer cell proliferation, antibacterial and antiviral effects[26-27]. Liu Yan et al. [28] used high-performance liquid chromatography to determine the average content of ellagic acid in blueberry fruit to be 6.893 mg/g. Ellagic acid has a whitening and freckle-reducing effect, can inhibit tyrosinase activity and block melanin production, and effectively remove age spots and sun spots [29].

1.6 Pterostilbene

Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene) is one of the functional ingredients in berries such as blueberries and grapes. Rodríguez-Bonilla et al. [30] used RP-HPLC to determine that the pterostilbene content in blueberries is 110 mg/100 g. Pterostilbene is a methylated derivative of resveratrol, which is more lipophilic than resveratrol and is more easily taken up by body cells [31]. Pterostilbene has a variety of biological activities, including anti-tumor, hypolipidemic, and anti-inflammatory effects, and has broad application prospects in dermatological diseases such as sun damage, antifungal, and skin tumors [32].

1.7 Superoxide dismutase

Superoxide dismutase (SOD) is a widely-occurring antioxidant metalloproteinase in living organisms. The SOD content in 100 g of fresh blueberries can reach 5. 39 IU[33] . SOD can catalyze the disproportionation of free radicals to form oxygen and hydrogen peroxide, and plays a key role in the balance between oxidation and antioxidants in the body. It is closely related to the occurrence and development of many human diseases. SOD can be divided into three categories according to different metal ions: blue-green eukaryotic cell cytoplasmic Cu, Zn-SOD, pink mitochondrial Mn-SOD, and tan-brown nuclear Fe-SOD. Studies[34] have confirmed that SOD plays a very important physiological role in the human body in terms of disease prevention, improving the body's immune system, anti-aging, anti-tumor, and anti-inflammatory effects.

1.8 Pectin

Pectin is a polysaccharide composed of galacturonic acid. It is widely found in the form of protopectin, pectin and pectic acid in the fruits, roots and stems of plants. Pectin has physiological effects such as inhibiting fat digestion and absorption, regulating blood sugar and inhibiting tumors. Low molecular weight pectin also has a certain effect of sobering up and preventing drunkenness[35] and can be used as a functional ingredient in the development of liver protection and hangover products. The total pectin content of blueberries can reach 4.1 g/kg[36]. Pectin is an important functional dietary fiber that gives blueberry foods an excellent texture and is also beneficial for reducing calorie intake and promoting intestinal health.

1.9 Vitamins and minerals

Blueberries contain 81 to 100 IU/100 g of VA and 2.7 to 9.5 μg/100 g of VE, which is much higher than the content of grapes and apples[37]. Blueberries are rich in trace elements, with contents of 220 to 920 μg/g of calcium, 2.0 to 3. 2 μg/g, phosphorus 98 ~ 274 μg/g, germanium 0.8 ~ 1.2 μg/g, magnesium 114 ~ 249 μg/g, iron 7.6 ~ 30.0 μg/g, zinc 2.1 ~ 4.3 μg/g[37].

1.10 Other nutrients

In addition to the main functional ingredients mentioned above, blueberries also contain fructose, fat, amino acids, protein and cellulose. The protein content of blueberries is 400 to 700 mg/100 g, containing 19 amino acids and 8 essential amino acids in the right proportions, the fat content is 500 ~ 600 mg/100 g, and the total acid content is 1.6% ~ 2.7% [37].

2 Health benefits of blueberries

2.1 Antioxidant

The theory of free radical oxidation is the theoretical basis for the mechanism of aging and many diseases in the human body. 80% to 90% of aging-related diseases are related to free radicals in the human body. Blueberries are rich in polyphenols such as anthocyanins and ellagic acid, which have strong free radical scavenging abilities. Zhou Xiaoli et al. [38] extracted a crude anthocyanin extract from blueberry pomace and determined its antioxidant activity, which showed that the blueberry anthocyanin free radical inhibition rate was similar to that of VC, and its antioxidant effect on lipids was stronger than that of VC. Zhang Zhuorui et al. [39] found that after 30 days of administering blueberry anthocyanins to mice by gavage, the total antioxidant capacity and total superoxide dismutase activity of the liver in mice fed anthocyanins were significantly higher than those in the control group, indicating that blueberries, which are rich in anthocyanins and phenolic acids, have good in vivo antioxidant effects. Free radicals and antioxidants are currently an important theoretical basis for diseases such as aging, tumors and cardiovascular diseases. The polyphenol components and good antioxidant activity of blueberries make them have broad application value and prospects in disease prevention and health maintenance.

2.2 Helps improve memory

The incidence of cognitive decline and neurodegenerative diseases in the elderly increases with aging. Research [40] has shown that blueberries have a significant preventive effect on age-related transient memory loss and can help improve memory. Yang Hongpeng et al. [41] found that blueberry anthocyanins can significantly improve memory function in mice, and the mechanism is related to reducing the accumulation of lipofuscin and improving antioxidant defense. Li Yawei et al. [42] further showed that blueberry anthocyanins can reduce the expression of NF-κB p65 and cleaved caspase-3 proteins in the hippocampus of mice induced by scopolamine, thereby significantly improving learning and memory disorders in mice, effectively reducing the number of platform jumping errors in mice, and significantly prolonging the latency period. Memory loss is closely related to age-related diseases. The health benefits of blueberries and their anthocyanins in improving memory may be related to their free radical scavenging effects in the body.

2.3 Eliminating eye fatigue and improving eyesight

Blueberry anthocyanins can promote blood circulation and maintain normal intraocular pressure [43]. Anthocyanins can promote the resynthesis of rhodopsin in retinal cells, thereby improving the dark adaptation of the human eye. Blueberries have adjuvant therapeutic effects on visual fatigue and amblyopia. Daily intake of 40 to 80 g of blueberries has a protective effect on eyesight [44]. Anthocyanins can be used to treat refractive errors, cataracts, glaucoma and other eye diseases [45]. As various types of vision problems are becoming increasingly prominent due to the worsening urban light pollution, the development of eye-care functional foods based on anthocyanins and their functions using blueberries as raw materials will greatly satisfy the huge potential market demand.

2.4 Prevention of cardiovascular and cerebrovascular diseases

In recent years, the incidence of cardiovascular and cerebrovascular diseases such as hypertension, hyperlipidemia and atherosclerosis has been increasing year by year, and these diseases are developing at a younger age. The occurrence and development of these diseases are closely related to modern people's eating habits. Research[46] found that the flavonoids contained in blueberries have obvious hypolipidemic activity. Li Yingchang et al. [47] found that after ingesting blueberry anthocyanins, the blood lipid levels and atherosclerosis index of hyperlipidemic rats were significantly lower than those of the high-fat group, while the activities of serum and liver T-AOC, SOD and GSH-Px were significantly enhanced, and the production of MDA was significantly reduced. Blueberry anthocyanins can regulate vasoconstriction and maintain normal blood pressure range, thereby protecting blood vessels and maintaining capillary permeability. Continuous consumption of blueberries at a dose of 200 g/d for 30 days can effectively improve cardiovascular function and lower systolic blood pressure [48]. The lipid-lowering function and antioxidant effect of blueberry anthocyanins may be the main reason and mechanism for their ability to reduce the risk of atherosclerosis.

2.5 Cancer prevention and treatment

Anthocyanins' remarkable anti-cancer effects are mainly achieved by scavenging active oxygen, reducing the production of oxidized DNA adducts and lipid peroxidation, and blocking cell proliferation [49]. Studies[49] have found that anthocyanins can effectively inhibit the occurrence of prostate cancer by inducing apoptosis of cancer cells, and prevent the occurrence of gastric cancer by blocking the synthesis of nitrites and scavenging nitrites. Lin Yang et al.[50] found that blueberry anthocyanins can significantly inhibit the proliferation of human colon cancer cells, upregulate the expression of the tumor suppressor gene p53, and effectively inhibit colon cancer cells. The treatment and prevention of cancer is a difficult and hot topic in the field of healthcare today. Safe and effective cancer prevention and treatment products are widely popular in the market. The active substances in blueberries, such as anthocyanins, ellagic acid and pterostilbene, have a clear mechanism of action and are highly safe for consumption in the prevention and treatment of cancer.

2.6 Weight loss

Obesity has been officially recognized as an epidemic disease, and research on the weight loss function and mechanism of blueberry anthocyanins has attracted widespread attention. When Yang Han et al. [51] studied the effects of wild blueberries and anthocyanin extracts on the intestinal flora of mice on a high-fat diet, they found that blueberry anthocyanin extracts can effectively improve the intestinal microecological imbalance of mice on a high-fat diet, exert a regulatory effect on the intestinal flora, and have a potential weight loss and fat loss effect. Other studies [52] have shown that anthocyanins can inhibit the proliferation and differentiation of pre-adipocytes, regulate the activity of adipocyte regulatory enzymes, and thus inhibit obesity. The mechanism by which blueberry anthocyanins intervene in obesity may also be related to inhibiting the expression of fatty acid synthesis genes, up-regulating the expression of lipid oxidation genes, and reducing the secretion of obesity-related factors [53].

2.7 Enhances immunity

Blueberry anthocyanins have been shown to promote the proliferation of mouse splenocytes and to synergize with ConA to promote the secretion of interferon-α and interleukin-2 by mouse splenocytes, with a certain dose-dependent effect [54]. Pterostilbene can work synergistically with VD to increase the expression of the cAMP gene and promote the body's immune function [55]. Hu Xiangyang et al. [56] studied the effect of Pterostilbene on the immune function of mice with stress load + hyperlipidemia and found that the immune indicators of T lymphocytes in the spleen of mice were elevated to varying degrees, which suggests that Pterostilbene has a certain effect on immunity. Therefore, Pterostilbene and anthocyanins in blueberries may be the main components affecting immunity.

2.8 Auxiliary hypoglycemic

Diabetes is a metabolic disorder syndrome characterized by hyperglycemia, and its pathological process involves multi-organ damage. Tian Mixia et al. [57] found that blueberry anthocyanins can significantly reduce the blood glucose levels and MDA levels in the livers of experimental diabetic mice, while maintaining the integrity of liver cells. Therefore, blueberry anthocyanins have a certain effect of enhancing the antioxidant capacity of liver tissue and protecting liver cells. Anthocyanins may control diabetes by promoting glucose absorption and glycogen synthesis, regulating lipids, intestinal flora balance, insulin synthesis and secretion, and pancreatic β-cell proliferation.

3 Development and utilization of blueberries

3.1 Blueberry common foods

Blueberries are suitable for making drinks because they yield more than 80% juice. Currently, the development of blueberry common foods mainly focuses on products such as drinks, fruit wines and jams. Currently, the main blueberry drinks on the market include fruit juice drinks, clear juice drinks, cloudy juice drinks, tea drinks, fruit pulp drinks, fruit vinegar drinks, solid drinks, lactic acid bacteria fermented drinks and compound functional drinks.

Blueberry wine products are becoming a new consumer hotspot in the fruit wine beverage industry due to their good health benefits and taste. Research and development of blueberry wine, blueberry fruit beer, and blueberry compound wine is increasing. Zheng Wanming [58] studied the process of blueberry wine and determined that the optimal enzymatic hydrolysis process conditions were a pectinase addition of 40 mg/L, an enzymatic hydrolysis temperature of 55 °C and an enzymatic hydrolysis time of 60 min, and that the optimal fermentation process was a yeast inoculum of 7%, an initial sugar content of 220 g/L, an initial pH of 4.0 and a main fermentation time of 8 d. Zhang Fangyan [59] studied the production process of a blueberry-kiwi composite fruit wine, obtaining a blueberry composite fruit wine with a rich fruity aroma, a transparent and bright appearance and a unique flavour. 0 and main fermentation time 8 d. Zhang Fangyan [59] studied the production process of blueberry-kiwi composite fruit wine, obtaining a blueberry composite fruit wine with a rich fruity aroma, a clear and bright appearance and a unique flavor.

Blueberries are rich in high methoxyl pectin and are suitable for making various jelly and jam foods. The recipe for blueberry jam with large fruit particles developed by Xia Qile et al. [60] is 40% fresh blueberries, 10% semi-dried fruit particles, 25% white granulated sugar, 20% fructose syrup, 5% water, 1% xanthan gum, 1% sodium alginate, and 0.2% citric acid. This process is time-consuming but suitable for industrial production. The low-sugar blueberry and rose complex health jam developed by Kou Can et al. [61] has a blueberry flavor and the unique aroma and texture of roses. It is sweet and sour and suitable for diabetics.

3.2 Blueberry health food

The development of blueberry health products is mainly based on the anthocyanin content of blueberries and their antioxidant effects. The main products include blueberry anthocyanin chewable tablets, blueberry anthocyanin eye protection capsules, blueberry lutein ester chewable tablets, blueberry cassia seed tablets, blueberry oral liquid, etc. Deng Yi et al. [62] used blueberries as the main raw material, combined with yellow essence, yam, kudzu root, medlar, etc., to develop a health drink with kidney-benefiting effects; Liu Junjun [63] prepared a functional drink with a combination of ginseng and blueberries, and evaluated its anti-fatigue function.

3.3 Blueberry cosmetics

Active ingredients such as anthocyanins, proanthocyanidins, flavonoids, superoxide dismutase, ursolic acid and arbutin can all be used in cosmetics. Blueberry arbutin and flavonoid substances can inhibit melanin formation and effectively remove blackheads, scars and dark circles under the eyes. Anthocyanin and other extracts can promote the formation of myogenin, making the skin smooth and elastic, and can be made into anti-wrinkle repair masks. The unique fresh fragrance of blueberry essential oil can be used in cosmetics such as wet wipes, masks and lipsticks. The product has a fresh and elegant flavor.

3.4 Other

Wu Jinming et al. [64] found that adding blueberry anthocyanins to cigarettes can significantly increase the smoothness and clarity of the smoke, reduce irritation, enhance the fruity aroma, and enhance the sweet aroma. Blueberry anthocyanins are also used in the development of natural antioxidant packaging materials because of their antioxidant and antibacterial properties.

4 Conclusion

In recent years, the cultivation of blueberries in China has expanded rapidly, and raw material resources are growing. However, due to insufficient technology and capacity for deep processing of products, a complete industrial chain has not yet been formed, resulting in few high value-added blueberry products with clear health benefits. In addition, due to the poor processing stability of polyphenols, improving the retention rate of polyphenols has become a key research direction in the field of blueberry processing.

Changes in the living environment and lifestyle have led to significant changes in the spectrum of human diseases, medical models and medical models. With the development of science and technology and the continuous improvement of living standards, people's understanding of health has been continuously improved, and the pursuit of health has become increasingly strong. Blueberries and their products are very much in line with the modern population's demand for healthy products that are natural and green, delicious, and disease-preventing, meeting the multidimensional physical and mental needs. Therefore, the blueberry industry has great potential for development and market growth.

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