Products from apple fruit

Apple fruit Nutrition facts

Delicious and crunchy, apple fruit are one of the most popular and favorite produces that health-conscious people who firmly believe in the concept of “health is wealth.” This wonderful fruit indeed is packed with rich phytonutrients that in the real sense indispensable for optimal health and wellness.

Certain proven antioxidants in apples have health promoting and disease prevention properties, and thereby, truly justifying the adage, “an apple a day keeps the doctor away.”

Scientific name: Malus domestica.

Apples are obtained from a medium-sized tree belonging to the Rosaceae family. The wild apple tree is thought to have originated in the mineral-rich mountain ranges of Kazakhstan. Today, its cultivation is fostered in many parts of the world, including the US, as a major commercial crop.

Apple fruit is oval or pear in shape. Its outer peel comes in different hues and colors depending upon the cultivar type. Internally, its crispy, juicy pulp is off-white to cream and features a mix of mildly sweet and tart flavor. Its seeds are bitter in taste, and therefore, inedible.

Hundreds of varieties of apples used for either table or dessert and cooking purposes are grown in the US and worldwide. Cooking apples tend to be larger, crispier and, tarter than dessert types.

Health benefits of Apple fruit

Delicious and crunchy apple fruit is notable for its impressive list of phtytonutrients, and antioxidants. Studies suggest that its components are essential for optimal growth, development, and overall wellness.

Apples are low in calories; 100 g of fresh fruit slices provide just 50 calories. They, however, contain no saturated fats or cholesterol. Nonetheless, the fruit is rich in dietary fiber, which helps prevent absorption of dietary-LDL or bad cholesterol in the gut. The fiber also saves the colon mucous membrane from exposure to toxic substances by binding to cancer-causing chemicals inside the colon.

Apples are rich in antioxidant phytonutrients flavonoids and polyphenolics. The total measured antioxidant strength (ORAC value) of 100 g apple fruit is 5900 TE. Some of the important flavonoids in apples are quercetin, epicatechin, and procyanidin B2.

Additionally, they are also good in tartaric acid that gives tart flavor to them. Altogether, these compounds help the body protect from harmful effects of free radicals.

Apple fruit contains good quantities of vitamin-C and β-carotene. Vitamin C is a powerful natural antioxidant. Consumption of foods rich in vitamin-C helps the body develop resistance against infectious agents and scavenge harmful, pro-inflammatory free radicals from the body.

Further, apple fruit is an ideal source of B-complex vitamins such as riboflavin, thiamin, and pyridoxine (vitamin B-6). Together, these vitamins help as co-factors for enzymes in metabolism as well as in various synthetic functions inside the human body.

Apples also carry small quantities of minerals like potassium, phosphorus, and calcium. Potassium is an important component of cell and body fluids that helps controlling heart rate and blood pressure; thus, counters the bad influences of sodium.

See the table below for in depth analysis of nutrients:

Apple fruit (Malus domestica), Fresh,

Nutrition value per 100 g, ORAC value-5900

(Source: USDA National Nutrient data base)

Principle Nutrient Value % of RDA Energy 52 Kcal 2.5% Carbohydrates 13.81 g 11% Protein 0.26 g 0.5% Total Fat 0.17 g 0.5% Cholesterol 0 mg 0% Dietary Fiber 2.40 g 6% Vitamins Folates 3 Вµg 1% Niacin 0.091 mg 1% Pantothenic acid 0.061 mg 1% Pyridoxine 0.041 mg 3% Riboflavin 0.026 mg 2% Thiamin 0.017 mg 1% Vitamin A 54 IU 2% Vitamin C 4.6 mg 8% Vitamin E 0.18 mg 1% Vitamin K 2.2 Вµg 2% Electrolytes Sodium 1 mg 0% Potassium 107 mg 2% Minerals Calcium 6 mg 0.6% Iron 0.12 mg 1% Magnesium 5 mg 1% Phosphorus 11 mg 2% Zinc 0.04 mg 0% Phyto-nutrients Carotene-Гџ 27 Вµg — Crypto-xanthin-Гџ 11 Вµg — Lutein-zeaxanthin 29 Вµg —

Selection and Storage

Keep fresh apples at room temperature for few days and in the refrigerator for up to two to three weeks. Wash them in clean, running cold water before use.

Preparation and Serving Tips

Wash apples thoroughly in the running water to remove any surface dust, insecticide/fungicide sprays. Trim off its stem-end using a paring knife, and cut the fruit into halves. Remove centrally placed, tiny, bitter seeds. Slice the fruit into desirable cubes or slices.

Apple pie.
Photo by: kanko

Here are some serving tips:

Eat apple fruit «as it is» along with its peel to get maximum health-benefits.

Sliced apple turns brown (enzymatic brownish discoloration) on exposure to air due to conversion in iron form from ferrous oxide to ferric oxide. If you have to serve them sliced, rinse slices in water added with few drops of fresh lemon.

Cloudy as well as clear apple juice is a healthy alternative drink with dinner.

Apple fruit is also used in the preparation of fruit jam, pie, and fruit salads.

Safety profile

Good apple fruit produce demands close attention and supervision of crops. According to the environmental working group reports, the apple fruit is one of the heavily pesticide-contaminated produces. The most common pesticides found in apples are organo-phosphorous and organochloride pesticides like Permethrin and DDT. Therefore, it is recommended to wash the fruit thoroughly before use. If possible, buy organic-certified apples. (Medical disclaimer).

≺≺- Back to Fruits from Apple fruit. Visit here for an impressive list of all variety of fruits with complete illustrations of their nutrition facts and health benefits.

Stanford School of Medicine Cancer information Page- Nutrition to Reduce Cancer Risk.

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Products from Apple fruit

A candy is a sugar based confectionery, made from concentrated sugar solution, to which they generally add the apple flavor, to produce yummy, mouth watering apple candies, which melts slowly in the mouth, with a rich taste of apple, for each and every swallow you do.

Though they are synthetic, quality branded candies are real and natural in taste. They give you the real taste of the fruit as such.

Since it is a product which has high concentration of sugar, bacteria or any other micro organisms will not be able to grow in candies.

Consequently, the shelf life of candies is longer than any other processed product of apple. It is applicable to only the hard candies, and not the soft candies which might not have a shelf life same as hard candies.

A good jam has a soft and even consistency with good fruit flavor, bright color and a semi jellied texture, that is easy to spread over, but has no free liquid.

Apple jam has the fresh flavor of ordinary apples. This jam can be relished by spreading a generous amount over a slice of bread with cheese or butter.

All jams are processed in a boiling water bath to prevent mold growth. The hot boiling jam is poured directly in to the jars in to which they have to be packed and sealed, the container is sterilized well before this action, generally processors leave a head space of � inch and then seal it.

Jams sealed aseptically has a long shelf life unlike homemade jams , it is due to the aseptic packaging at the same time the preservatives and amount of sugar used to prepare the jam, sugar itself acts as a preservative.

Apple Jelly is a semi solid food made from fruit juice, sugar and pectin. Generally the pectin present in the fruit should act as a gelling agent, but since it is insufficient to form a proper gel, pectin is added externally to help enhance the gelling capacity.

It is a clear or translucent fruit spread, made from sweetened fruit juice and set using naturally occurring pectin present in the fruit or by adding pectin if it is inadequate. Flavoring and coloring is also added in order to enhance the quality and acceptability of the product.

Jelly’s are packed either in plastic cups with a seal or in sterilized glass bottles or jars leaving half an inch of head space before placing the caps.

Apple jellies are manufactured using the clarified concentrate of the fruit. They have an excellent rich apple flavor which is soft and smooth which just slides from your mouth into the tract silkily.

Apple juice is one of the fruit juice which is manufactured by maceration and pressing of apples. The expelled juice is further processed by centrifugal and enzymatic clarification to remove the pectin and starch.

The resulting juice just holds the fine particulate in suspension which is then pasteurized for packing in glass, metal or aseptic processing system containers.

There is also unfiltered fresh apple juice without further processing which is also packaged and sold in markets, but generally when they refer to apple juice; they mean the clarified and pasteurized one, which is commonly known as apple cider.

Apple pulp is manufactured by picking fresh fruits, which are clean, sound and properly matured. The fruit and the pulp is processed and packed in accordance with proper manufacturing practices, following aseptic packaging.

The fruit as such as slices or as pulp is pre heated and then packaged. These kind of pulp or slices apples are mostly used in the processing of apple juice and then they are sold as such. Apple pulp is used in making of cookies, cakes, muffins and other such bakery products.

The slices of apple are also used in cakes or as a decorative in bakery products; they are also eaten as such. Since it is packaged in aseptic method, they generally have a long shelf life.

Apple juice concentrate is generally produced by evaporating the fresh apple juice, which is extracted from farm fresh juicy apples. Fresh apple juice has a concentration of around 11 to 13 brix. Evaporating the fresh juice, yields a good apple concentrate.

This is very helpful for packaging and the same time reduces the spoilage, giving an extended shelf life.

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Apple fruit

Apple (Malus sp., Rosaceae) is cultivated worldwide as a fruit tree, and is the most widely grown species in the genus Malus. The apple tree originated in Central Asia, where its wild ancestor, Malus sieversii, is still found today. Apples have been grown for thousands of years in Asia and Europe, and were brought to North America by European colonists.

Apples are popular because of the many ways that they can be consumed and because of their convenience and durability. Apples can be processed into sauce, slices, or juice and are favored for pastries, cakes, tarts, and pies.

The apple pulp has been processed into candies (fruit leathers) and used as a source of pectin. The apple juice can be consumed fresh, either natural or filtered, fermented into alcoholic beverages such as cider or wine, distilled into brandy, or transformed into vinegar.

Is apple a fruit ?

By definition, a fruit is the sweet and fleshy product of a tree or other plant that contains seed and can be eaten as food.

In fact apples are common fruits consumed worldwide!

Apple fruit facts

The apple fruit matures in late summer or autumn and cultivars exist with a wide range of sizes. Commercial growers aim to produce an apple that is 7.0 to 8.3 cm (2.75 to 3.25 in) in diameter, due to market preference. Some consumers, especially those in Japan, prefer a larger apple, while apples below 5.7 cm (2.25 in) are generally used for making juice and have little fresh market value. The skin of ripe apples is generally red, yellow, green, pink, or russetted although many bi- or tri-colored cultivars may be found 1) . The skin may also be wholly or partly russeted i.e. rough and brown. The skin is covered in a protective layer of epicuticular wax 2) . The exocarp (flesh) is generally pale yellowish-white, though pink or yellow exocarps also occur.

Commercially, apples can be stored for some months in controlled atmosphere chambers to delay ethylene-induced ripening. Apples are commonly stored in chambers with higher concentrations of carbon dioxide and high air filtration. This prevents ethylene concentrations from rising to higher amounts and preventing ripening from occurring too quickly. Ripening continues when the fruit is removed from storage. For home storage, most cultivars of apple can be held for approximately two weeks when kept at the coolest part of the refrigerator (i.e. below 5 °C). Some, including ‘Granny Smith’ and ‘Fuji’, can be stored up to a year without significant degradation.

Non-organic apples may be sprayed with 1-methylcyclopropene blocking the apples’ ethylene receptors, temporarily preventing them from ripening.

Apple nutrition facts

A typical apple serving weighs 242 grams and provides 126 calories with a moderate content of dietary fiber (Table 1). Otherwise, there is generally low content of essential nutrients.

Apples are a rich source of various phytochemicals including flavonoids (e.g., catechins, flavanols, and quercetin) and other phenolic compounds (e.g., epicatechin and procyanidins) found in the skin, core, and pulp of the apple 3) .

Phenolic compounds, such as polyphenol oxidase, are the main driving force behind browning in apples. Polyphenol oxidase catalyzes the reaction of phenolic compounds to o-quinones causing the pigment to turn darker and therefore brown.

Ideain (cyanidin 3-O-galactoside) is an anthocyanin, a type of pigment, which is found in some red apple cultivars 4) .

Phlorizin is a flavonoid that is found in apple trees, particularly in the leaves, and in only small amounts if at all in other plants, even other species of the Malus genus or related plants such as pear trees 5) .

Table 1. Apple (raw with skin) nutrition facts

Nutrient	Unit		Value per 100 g
Approximates
Water	g		85.56
Energy	kcal		52
Energy	kJ		218
Protein	g		0.26
Total lipid (fat)	g		0.17
Ash	g		0.19
Carbohydrate, by difference	g		13.81
Fiber, total dietary	g		2.4
Sugars, total	g		10.39
Sucrose	g		2.07
Glucose (dextrose)	g		2.43
Fructose	g		5.9
Lactose	g		0
Maltose	g		0
Galactose	g		0
Starch	g		0.05
Minerals
Calcium, Ca	mg		6
Iron, Fe	mg		0.12
Magnesium, Mg	mg		5
Phosphorus, P	mg		11
Potassium, K	mg		107
Sodium, Na	mg		1
Zinc, Zn	mg		0.04
Copper, Cu	mg		0.027
Manganese, Mn	mg		0.035
Selenium, Se	µg		0
Fluoride, F	µg		3.3
Vitamins
Vitamin C, total ascorbic acid	mg		4.6
Thiamin	mg		0.017
Riboflavin	mg		0.026
Niacin	mg		0.091
Pantothenic acid	mg		0.061
Vitamin B-6	mg		0.041
Folate, total	µg		3
Folic acid	µg		0
Folate, food	µg		3
Folate, DFE	µg		3
Choline, total	mg		3.4
Betaine	mg		0.1
Vitamin B-12	µg		0
Vitamin B-12, added	µg		0
Vitamin A, RAE	µg		3
Retinol	µg		0
Carotene, beta	µg		27
Carotene, alpha	µg		0
Cryptoxanthin, beta	µg		11
Vitamin A, IU	IU		54
Lycopene	µg		0
Lutein + zeaxanthin	µg		29
Vitamin E (alpha-tocopherol)	mg		0.18
Vitamin E, added	mg		0
Tocopherol, beta	mg		0
Tocopherol, gamma	mg		0
Tocopherol, delta	mg		0
Vitamin D (D2 + D3)	µg		0
Vitamin D	IU		0
Vitamin K (phylloquinone)	µg		2.2
Lipids
Fatty acids, total saturated	g		0.028
04:00:00	g		0
06:00:00	g		0
08:00:00	g		0
10:00:00	g		0
12:00:00	g		0
14:00:00	g		0.001
16:00:00	g		0.024
18:00:00	g		0.003
Fatty acids, total monounsaturated	g		0.007
16:1 undifferentiated	g		0
18:1 undifferentiated	g		0.007
20:01:00	g		0
22:1 undifferentiated	g		0
Fatty acids, total polyunsaturated	g		0.051
18:2 undifferentiated	g		0.043
18:3 undifferentiated	g		0.009
18:04:00	g		0
20:4 undifferentiated	g		0
20:5 n-3 (EPA)	g		0
22:5 n-3 (DPA)	g		0
22:6 n-3 (DHA)	g		0
Fatty acids, total trans	g		0
Cholesterol	mg		0
Phytosterols	mg		12
Amino Acids
Tryptophan	g		0.001
Threonine	g		0.006
Isoleucine	g		0.006
Leucine	g		0.013
Lysine	g		0.012
Methionine	g		0.001
Cystine	g		0.001
Phenylalanine	g		0.006
Tyrosine	g		0.001
Valine	g		0.012
Arginine	g		0.006
Histidine	g		0.005
Alanine	g		0.011
Aspartic acid	g		0.07
Glutamic acid	g		0.025
Glycine	g		0.009
Proline	g		0.006
Serine	g		0.01
Other
Alcohol, ethyl	g		0
Caffeine	mg		0
Theobromine	mg		0
Anthocyanidins
Cyanidin	mg		1.6
Petunidin	mg		0
Delphinidin	mg		0
Malvidin	mg		0
Pelargonidin	mg		0
Peonidin	mg		0
Flavan-3-ols
(+)-Catechin	mg		1.3
(-)-Epigallocatechin	mg		0.3
(-)-Epicatechin	mg		7.5
(-)-Epicatechin 3-gallate	mg		0
(-)-Epigallocatechin 3-gallate	mg		0.2
(+)-Gallocatechin	mg		0
Flavanones
Hesperetin	mg		0
Naringenin	mg		0
Flavones
Apigenin	mg		0
Luteolin	mg		0.1
Flavonols
Kaempferol	mg		0.1
Myricetin	mg		0
Quercetin	mg		4
Isoflavones
Daidzein	mg		0
Genistein	mg		0
Glycitein	mg		0
Total isoflavones	mg		0
Formononetin	mg		0
Coumestrol	mg		0
Proanthocyanidin
Proanthocyanidin dimers	mg		13.2
Proanthocyanidin trimers	mg		8
Proanthocyanidin 4-6mers	mg		24.7
Proanthocyanidin 7-10mers	mg		19.2
Proanthocyanidin polymers (>10mers)	mg		28.8

[Source: United States Department of Agriculture Agricultural Research Service 6) ]

Apple fruit benefits

Apples are a rich source of dietary phytochemicals such as flavonoids. They also contain high levels of polyphenols and other phytochemicals 7) . Polyphenols in apples and their extracts (juices) have been studied in several human studies that have shown promising results related to their beneficial effects 8) . For example, consumption of at least one apple a day was reported to reduce the risk of colorectal cancer 9) . The study also predicted that the risk of colorectal cancer reduced by approximately 50% upon consumption of more than one apple a day. In many laboratory test tubes and animals studies on the anticancer effects of apple extracts have been evaluated, including those of phytochemical compounds in these extracts 10) , 11) and apple juice fractions 12) .

In previous studies, it was demonstrated that phloretin isolated from apple peels exhibits significant antihepatic tumor proliferation capacity through in animal study via the inhibition of type 2 glucose transporter (GLUT2) 13) . A study further demonstrated that phloretin significantly potentiates paclitaxel-induced DNA laddering effects in a human liver cancer cell model 14) . This observation indicated that phytochemical components in apples exhibit a beneficial effect on human health.

For cancer chemoprevention, dietary nutrients should be more readily available. Many studies have demonstrated the chemopreventive effects of dietary polyphenols, especially the most abundant subclasses, including flavonoids (60% of all polyphenols) and phenolic acids (30% of total polyphenols) 15) . Flavonoids are divided into various groups based on their molecular structure, several of which are present in significant quantities in apple, including flavanols, flavonols, and anthocyanidins as well as dihydrochalcones and hydroxycinnamic acids 16) , 17) . The chemical structures of several representative polyphenols present in apple are shown in Figure 1 18) .

Figure 1. Chemical structures of some selected typical biocompounds in apple juice

Apple and cardiovascular disease prevention

A clinical trial evaluated the cardiovascular protective effects of consumption of 75 g (about two medium-sized apples) of dried apple for 1 year in 146 postmenopausal women 20) . The study showed that dried apple significantly lowered serum levels of total cholesterol and LDL “bad” cholesterol by 9% and 16%, respectively, at 3 months and further decreased by 13% and 24%, respectively, at 6 months, but stayed constant thereafter 21) . Furthermore, consumption of dried apple also reduced lipid hydroperoxide and C-reactive protein (a blood test marker for inflammation in the body) 22) . In addition, a study 23) compared the cholesterol-lowering effect of 5 different apple species, Red Delicious, Granny Smith, Fuji, Golden Delicious and Annurca apple, in mildly hypercholesterolaemic healthy subjects. The study 24) detected that Annurca apples led to the most significant outcome, reduced total cholesterol and LDL “bad” cholesterol levels by 8.3% and 14.5%, respectively, and an increased HDL “good” cholesterol level by 15.2% 25) . Moreover, another study 26) compared the effects of whole fresh apple and processed apple products (apple pomace, cloudy apple juice, or clear apple juice) on lipid profiles in healthy volunteers. The result showed that whole apple, pomace, and cloudy juice lowered serum total cholesterol and LDL “bad” cholesterol; however, clear apple juice increased total cholesterol and LDL “bad” cholesterol slightly, from which it could be concluded that the fiber component was necessary for the lipid-lowering effect of apple in healthy humans. Additionally, the acute effects of apple on improving endothelial function were studied in some trials, showing that apple improved endothelial function by affecting nitric oxide metabolites 27) , 28) .

Antioxidant activity of apple polyphenols

Generation of oxygen radicals causes chronic diseases such as diabetes mellitus 29) , retinal degeneration, neurodegenerative disorders, aging, and cancer. Several studies have demonstrated that apple polyphenols, including phloretin, exhibit promising antioxidants effects by playing a role in significant mechanisms responsible for the prevention of illnesses triggered by oxidative stress 30) . For example, in a previous study on Wistar rats, diabetes was induced by a single dose of streptozotocin. Rats in the diabetic group received either apple juice (15 mL/kg) or apple peel extract (1 g/kg) for 21 days. At the end of the study, lipid profile parameters were measured in serum samples and lipid peroxidation level, antioxidant enzyme activities, and level of inflammatory markers were evaluated in pancreatic tissue samples. The study concluded that supplementation with apple juice/extract may have protective effects against deleterious complications of diabetes mellitus due to its antioxidant effects 31) . In a different study on human participants, after 2 weeks of dietary intervention in 25 healthy individuals, the influence of apple and grape juices consumption on body antioxidant status was investigated. The results indicated that such a dietary consumption increased their plasma total antioxidant capacity and decreased their serum and plasma concentration of malondialdehyde 32) .

Anticancer activity of apple polyphenols

In addition to its antioxidant activity, studies 33) , 34) , 35) have demonstrated that apple polyphenols have significant effects in affecting signaling pathways that control cell survival, growth, and proliferation both in vitro and in vivo. The results have shown that phloretin inhibited proliferation and induced apoptosis in nonsmall cell lung cancer cells (A549, Calu-1, H838, and H520) in a dose-dependent manner; phloretin also suppressed the invasion and migration of these cells. In one study, it was found that phloretin (50–150μM) significantly potentiates paclitaxel (10nM)-induced DNA laddering formation in human hepatoma (Hep G2) cells. The antitumor therapeutic efficacy of phloretin (10 mg/kg body weight) was determined by combined treatment of cells with antitumor drug (paclitaxel, 1 mg/kg body weight) in an SCID mouse model 36) . Recently it was also further demonstrated that apple phloretin inhibits human colorectal cancer and liver cancer cells through inhibition of GLUT2 (Figure 2). These results further provide evidence to the hypothesis that glucose deprivation therapy has some important beneficial effects on human cancer therapy 37) . To test this hypothesis, another group evaluated the antiproliferative activity of apple juices in vitro in MCF-7 and MDA-MB-231 human breast cancer cells. The study results showed that Pelingo apple juice has promising effects to inhibit breast cancer cell proliferation 38) . It was demonstrated that 3-beta-trans-cinnamoyloxy-2alpha-hydroxy-urs-12-en-28-oic acid, which is one of the main components of apple peels, showed potent in vitro and in vivo antitumor activity against mammary tumor in a nude mouse xenograft model at a dose of 50 mg/kg/d without body weight loss and mortality 39) .

Figure 2. Apple polyphenol phloretin inhibits growth of cancer cells through inhibition of type 2 glucose transporter

Apple polyphenols inhibit cell migration and invasion

Antimetastasis effects of biocompounds in apple have been studied by our group. Our results have indicated that phloretin is an inhibitor of GLUT2 41) and that targeting GLUT2 significantly inhibited COLO 205 colon cancer cell proliferation, migration, and invasion in vitro and in vivo 42) . In this study 43) , p53-mediated signals were important. Inhibition of the wild-type p53 by dominant negative p53 will attenuate the phloretin-induced colon cancer migration and its related signals. In colorectal cancers, studies have demonstrated that the activation of nuclear factor-κB (NF-κB) occurs via lipopolysaccharide (LPS) binding to the Toll-like receptor 4 (TLR4). Modification of polysaccharide components in apple altered the LPS/TLR4/NF-κB pathway; consequently, supplementation of apple polysaccharide significantly inhibited the migratory ability in vitro on the LPS/TLR4/NF-κB pathway in colorectal cancer cells (HT-29 and SW620 cells) 44) . In a study on liver cancer cells, the effect of apple polyphenol extract on the proliferation and invasion of rat ascites hepatoma cell line (AH109A) was examined in vitro. The apple polyphenol extract suppressed both proliferation and invasion of the hepatoma cell line in a dose-dependent manner up to 200 μg/mL. In an in vivo study, apple polyphenol also reduced the growth and metastasis of solid hepatomas and significantly suppressed the serum lipid peroxide level in rats transplanted with AH109A 45) .

Apple polyphenols induced apoptotic cancer cell death

Previous results demonstrated that apple polyphenol phloretin (50–150μM) significantly potentiates paclitaxel (10nM)-induced DNA laddering formation in Hep G2 cells. It was also demonstrated that the caspases 3, 8, and 9 were involved in apoptosis, as evidenced by activity assays 46) . Previous studies in this area have also demonstrated that phloretin inhibited leukemia cell growth 47) and induced apoptosis of melanoma cells through deprivation of glucose uptake by inhibition of glucose transmembrane transport 48) . Using 18F-fluorodeoxyglucose micropositron emission tomography the effects of phloretin-induced suppression of liver tumor growth were demonstrated to involve regulation of glucose transportation. The 18F-fluorodeoxyglucose uptake in the phloretin-treated Hep G2 tumor-bearing mice was significantly suppressed as compared with the control mice. Effects of phloretin on glioblastoma cancer cells have been investigated via induction of apoptosis and cells’ growth cycle arrest. The identified mechanisms demonstrated increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclin D, and cyclin E. Moreover, the phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin (PI3K/Akt/mTOR) signaling cascades were suppressed by phloretin in a dose-dependent manner 49) . Phloretin-based combination treatment enhanced the anticancer effects of cisplatin on nonsmall cell lung cancer cell lines by suppressing the expression of Bcl-2, increasing the protein expression of cleaved caspases 3 and 9, and deregulating the expression of matrix metalloproteinase-2 and metalloproteinase-9 on gene and protein levels 50) . The results suggest that inhibition of intracellular glucose uptake was the most important mechanism responsible for the cancer cell killing effects. Because many cancer cells rely on aerobic glycolysis for energy production, Xintaropoulou et al 51) targeted this pathway as a potential strategy to inhibit cancer cell growth. In that study, inhibition of five glycolysis pathway molecules (GLUT1, HKII (hexokinase II), PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), PDHK1 (pyruvate dehydrogenase kinase I), and LDH (lactate dehydrogenase)) using nine inhibitors (phloretin, quercetin, STF31 (Glut1 inhibitor), WZB117 (Glut1 inhibitor), 3PO (3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one, glycolytic inhibitor), 3-bromopyruvate, dichloroacetate, oxamic acid, NHI-1 (lactate dehydrogenase A inhibitor)) was investigated in panels of breast and ovarian cancer cell line models. Their results indicated that growth of breast and ovarian cancer cell lines was more sensitive to the glycolytic pathway, with increased sensitivity to the inhibitors under normoxic conditions 52) .

Signaling molecules and disease protection effects of phloretin

As described earlier, apple polyphenols induced anticancer activity mainly through their antioxidant activity. Such results have been confirmed by basic in vitro studies. Moreover, phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclin D, and cyclin E 53) . Inhibition of intracellular signaling pathways as well as the PI3K/Akt/mTOR and ERK/Nrf2 signaling cascades was suppressed by phloretin in a dose-dependent manner 54) . In addition, many previous studies have also proposed that phloretin triggered the mitochondrial apoptosis pathway 55) , 56) and generated reactive oxygen species (ROS) 57) . Most of these studies were accompanied by induction of cell growth arrest and apoptosis through upregulation of proapoptotic molecules such as Bax, Bak, and poly (ADP-ribose (adenosine diphosphate-ribose)) polymerase (cleaved) and downregulation of Bcl-2. The antioxidant agents N-acetyl-l-cysteine and glutathione weakened the effect of phloretin on glioblastoma cells. In conclusion, these results demonstrate that phloretin exerts a potent chemopreventive activity in human glioblastoma cells through the generation of ROS. Such effects may have some potential applications for clinical patients. For example, in acute hepatitis patients, liver damage is induced by several damaging factors, among which viral exposure, alcohol consumption, and drug and immune system issues are most popular 58) . In addition to antioxidant effects, phloretin is also able to modulate inflammatory responses. A previous study demonstrated that phloretin suppressed the activation and function of mouse dendritic cells 59) . The study results showed that phloretin disturbed the multiple intracellular signaling pathways in dendritic cells induced by the TLR4 agonist LPS, including ROS, mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase), and NF-κB, thus reducing the production of inflammatory cytokines and chemokine 60) .

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