**7. Health perspectives of wheat antioxidants**

There are multiple evidences which prove that utilization of wheat antioxidants is linked with the lower incidence of oxidative stress-related chronic diseases and age-related disorders, such as carcinogenesis, cardiovascular diseases, type II diabetes, and obesity. They perform health-endorsing perspectives due to the presence of vitamin C, vitamin E, carotenoids, phenolic acids, and flavonoids [25, 26]. They also facilitate digestion in human body by allowing the bound phenolics in the colon [67]. Similarly, they improve insulin and inhibit the tumor necrosis factor (TNF) alpha serum levels, lowering the serum cholesterol, fasting glucose, and triglyceride. They also exert anticancer effects on cell growth and apoptosis of human breast cancer cells such as MCF-7 and MDA-MB-231 [72].

The fact is that diet can completely change the life quality and human health. Wheat has numerous essential nutrients, which are important part of diet. It is one of the most dominating nutritious crops. Intake of whole grain or wheat reduces the cardiovascular risk and diabetes [73]. The antioxidants of wheat and the insoluble fibers impart the valuable properties. Nevertheless, metabolism and cholesterol biosynthesis are directly standardized through wheat antioxidants as compares to antioxidative agents, which are acting simply. The productive impacts are examined regarding the effect of antioxidants present in wheat on the enzymes which participate in cholesterol biosynthesis.

materials depends mainly on the bioavailability and absorption of soluble/ insoluble and free/

In case of insoluble fiber, the greater number of bound ferulic acid, for example, wheat bran, is believed to evade from the stomach or intestinal digestion or absorption to hold out the colon. Microbial enzymes of the colon, for instance, esterase and xylanase, release and solubilize feruloylated oligosaccharides (FOs) (i.e., feruloyl-arabinoxylan, 5-o-feruloyl-arabinofuranose) or free ferulic acid, just after reaching the colon. An esterase from mucosa acts on a part of bound ferulic acid during the flow within the gastrointestinal tract leading to the colon, and feruloylated oligosaccharides or free ferulic acid is released [68, 69]. The newly emancipated phenolic acid is absorbed through the gastrointestinal epithelium into the bloodstream jointly with ingested free phenolic acid and delivered to various tissues. The microbial esterases and mucosal substrates like 5-o-feruloyl-arabinofuranose are examples of soluble free and conjugate phenolic acids which are used for absorption of nutrients [70].

In short, phenolic acid in wheat which is of various forms (i.e., insoluble, soluble, and free conjugated bound forms) is converted by the breakdown reaction of free phenolic acid involving colonial and mucosal enzymes. These free phenolic acids destined to blood stream after distribution and metabolized into the body by the action of different enzymes. Wheat phenolic acids have different stages where various factors affects absorption and bioavailability. These factors include (a) the absorption of phenolic acids in the lumen of digestive system and capacity of the biomembrane and monocarboxylic acid transporter; (b) conjugating enzyme susceptibility, tissue having free phenolic acid metabolism, and transporter of monocarboxylic acid affinity; (c) ingestion of wheat phenolic acid, phenolic acid-bound content in conjugated, free, insoluble, and soluble; and (d) discharge of free phenolic content and soluble and insoluble bound of phenolic acid which are attacked by enzymes and the area of GI tract. In recent studies the effect of ingested food components having phenolic acid has been discussed in Ref. [71]. The health benefits of whole grain such as rice and wheat should be studied in detail to find the effect of different aspects on bioavailability and absorption of phenolic acid present in wheat.

There are multiple evidences which prove that utilization of wheat antioxidants is linked with the lower incidence of oxidative stress-related chronic diseases and age-related disorders, such as carcinogenesis, cardiovascular diseases, type II diabetes, and obesity. They perform health-endorsing perspectives due to the presence of vitamin C, vitamin E, carotenoids, phenolic acids, and flavonoids [25, 26]. They also facilitate digestion in human body by allowing the bound phenolics in the colon [67]. Similarly, they improve insulin and inhibit the tumor necrosis factor (TNF) alpha serum levels, lowering the serum cholesterol, fasting glucose, and triglyceride. They also exert anticancer effects on cell growth and apoptosis of human breast

The fact is that diet can completely change the life quality and human health. Wheat has numerous essential nutrients, which are important part of diet. It is one of the most dominating nutritious crops. Intake of whole grain or wheat reduces the cardiovascular risk and

**7. Health perspectives of wheat antioxidants**

cancer cells such as MCF-7 and MDA-MB-231 [72].

conjugate phenolic acids.

372 Wheat Improvement, Management and Utilization

The expression of genes involved in metabolism and cholesterol biosynthesis are examined by the wheat antioxidants. Wheat antioxidants at a concentration of 0.12 mg/mL are treated with the rat hepatocytes which is equivalent to 2 mg of wheat grain /mL of medium for 24 hours. Ribonuclease protection assay (RPA) are used for the examination of mRNA levels of HMG-CoA reductase (HMG-CoA-R), LDL receptor (LDLR) and cholesterol 7R-hydroxylase (CYP7A1). CYP7A1 and HMG-CoA-R are rate limiting enzymes for the conversion of cholesterol to bile acids and cholesterol biosynthesis respectively. It is precisely evident that wheat antioxidants considerably boosted the breakdown of HMG-CoA-R mRNA due to the progressive studies of impacts of wheat antioxidants on the mRNA stabilities of HMG-CoA-R and CYP7A1 but rise the CYP7A1 mRNA stability. Wheat antioxidants also participate in continuous boosting of bile synthesis. The data concludes that the control of the important genetic factors participating in metabolism and biosynthesis may be illustrated as among basic and important mechanism on molecular/cellular bases due to which the dangers of heart-related disorders are reduced by wheat antioxidants [74].

The polyphenols from wheat have been proven effective against cervical cancer cells (HeLa) and colon cancer cells (HT-29 and Caco-2) due to their antioxidant potential and induction of apoptosis and inhibit the proliferation of uncontrolled growth of cell lines [75]. Similarly, in human neuroblastoma cells (SH-SY5Y), they enhanced the viable cell numbers by 37%, lowered the release of lactate dehydrogenase, suppressed the H<sup>2</sup> O2 -induced formation of reactive oxygen species, and maintained the mitochondrial transmembrane potential. They also enhanced the Bcl-2/Bax ratio and blocked cleavage poly(ADP-ribose) polymerase by inhibiting caspase-3 activation [76]. They also exert anticancer effects on cell growth and apoptosis of human breast cancer cells such as MCF-7 and MDA-MB-231. Wheat bran is rich in alkylresorcinols (ARs), and having colon cancer cell lines (HT-29 and HCT-116) through increasing or decreasing the side-chain lengths, it diminished the activities. On the aromatic ring of the AR analogue, there are two hydroxyl groups at C-1 and C-3, greatly contributed to their antitumor activity. There is no significant enhancement in activity against HCT-116 cells on the third hydroxyl group at C-2 into the aromatic ring of the AR analogues [77]. Moreover, wheat bioactive compounds caused significant reduction in lipid peroxidation (LPO) and enhancement in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in Swiss albino mice [78]. Similarly, the administration of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) (24 μmol/l) from fermented wheat germ extract (FWGE) exhibited the antiproliferative properties in vitro in nine human cancer cell lines after 24 h of culture by causing cell cycle arrest, inducing apoptotic cell death and neutralizing the effect of reactive oxygen species [79]. Ferulic acid is another promising antioxidant of wheat that induced the apoptotic cell death in human breast cancer cells such as MCF-7, MDA-MB-231, osteosarcoma 143B, and MG63 cells lines in dose-dependent fashion through multiple mechanisms such as (1) induction of apoptosis; (2) caused G0/G1 phase arrest, enhancement of caspase-3 activity; (3) downregulation of the expression of cell cycle-related protein, CDK 2, CDK 4, and CDK 6; (4) downregulation of Bcl-2 expressions, upregulation of Bax, and inhibition of PI3K/Akt activation [80, 81]. In another study conducted by [82], wheat ethanolic extracts provide protection to hepatic microsomes through reducing the proliferation of the HCT 116 and A549 cancer cell lines. The *in vivo* inclusion of β-Glucans has a great potential against number of conditions like tumor development and infections caused by fungal, viral, prozoal and bacterial pathogens [83]. It also activates the T-helper and natural killer (NK) cells, cytotoxic macrophages, and promotion of T-lymphocyte differentiation and activation [84]. Wheat polyphenols are used to resolve the problem of septic discharge from the ear, relieve ear pain, and eliminate scars [85]. These polyphenols also prevented from the oxidative damage of DNA, proteins, and membrane lipids as well as also protected from the incidence of cardiovascular and cancer [86]. They also suppress the LDL oxidation through binding with apolipoprotein B [87]. Alkylresorcinol from wheat bran suppresses the platelet binding to fibrinogen, stimulates the thromboxane production, and inhibits triglyceride accumulation. In human erythrocytes, they also prevent from the free radical-induced oxidative damage [88, 89]. Wheat antioxidants are also effective to reduce the accumulation of triglycerides, low-density lipoprotein, reactive oxygen species, and concentration of thiobarbituric acid-reactive substances (TBARS) and enhance the high-density lipoprotein, vitamin E, and vitamin A [90]. They also improved insulin, suppressed the tumor necrosis factor (TNF) alpha serum levels, and lowered the serum cholesterol, triglyceride, and blood sugar [72]. The bioactive compounds, such as ferulic acid, tocopherols, and carotenoids, significantly increased the liver glycogen and lowered the glycosylated hemoglobin levels and blood glucose [76, 91, 92].
