Functional Foods For Chronic Disease Prevention: Epidemiological evidence shows that regular consumption of functional foods, value-added food products, and nutraceuticals is associated with a lowered risk of coronary heart disease, obesity. diabetes: cancer, osteoporosis, and other chronic age-related degenerative diseases like Parkinson’s and Alzheimer’s diseases. For example, Berry fruits and blackcurrants are employed in folk medicine for the prevention and treatment of circulatory disorders and inflammatory diseases. These foods are known to play important roles in modulating oxidative stress in disease states Their observed health benefit has been attributed to the presence of bioactive compounds which accumulate in plasma and tissues of consumers about dietary intakes. They play a role in inhibiting reactions mediated by reactive oxygen species.
Plant foods such as vegetables, fruits, cereals, spices, and legumes have been reported to play crucial roles in the protection against and prevention of various chronic diseases such as diabetes, obesity, cancer, erectile dysfunction, cardiovascular diseases, and Alzheimer’s disease by modulating several metabolic processes. Functional food bioactive compounds are extra nutritional constituents that occur naturally in plants and can exert a biological effect.
Intake of natural dietary bioactive compounds is associated with a low incidence of these chronic diseases. Epidemiological, clinical, and biochemical studies have revealed that these bioactive compounds through different mechanisms have various activities in the human body such as antioxidant, antidiabetic, antihypertensive, anti-alchemic, antiproliferative, and antimicrobial activities. These unique properties have been linked to some bioactive food components that can promote health and prevent diseases.
The biological effects of these chemicals present in food and food-related products may be associated with their affinity for certain proteins, via inhibition or modulation of some enzymes, and their antioxidant activity. Moreover, the antioxidant activities of bioactive compounds from plant foods have been widely studied because of their negative correlation with oxidative stress-mediated diseases. More than 8,000 bioactive compounds, including polyphenols, terpenoids, carotenoids, alkaloids, omega-3, and polyunsaturated fatty acids, have been identified in plants, and there are many yet to be discovered.
Degenerative or chronic diseases such as cancer, platelet aggregation, thrombosis, sexual dysfunction, arthritis, diabetes, obesity, stroke, and respiratory, cardiovascular, and neurodegenerative diseases are among the leading causes of morbidity and mortality globally. Degenerative diseases have a highly significant impact on health, quality of life, and life expectancy. These diseases are rapidly increasing worldwide and have contributed approximately 60% of the 56.5 million total reported deaths in the world and approximately 46% of the global burden of disease. About half of the total deaths arising from chronic diseases are associated with cardiovascular diseases and a high percentage can also be attributed to obesity and diabetes, which now occur early in life.
Cardiovascular disease (CVD) and cancer are the top two leading causes of death in many countries of the world. It has been projected that by 2020 chronic diseases will account for almost three-quarters of all deaths worldwide and that 71% of deaths are due to ischemic heart disease (IHD), 75% of deaths due to stroke, and 70% of deaths due to diabetes will occur in developing countries. Epidemiological and experimental studies have shown that high consumption of fruits, vegetables, spices, beverages, legumes, whole grains, and fish, a high fiber diet, and other food-related products can be strongly linked to reduced risk of chronic diseases such as CVD, cancer, diabetes, Alzheimer’s disease, sexual dysfunction, cataracts, and age-related functional decline, which can be attributed to the bioactive compounds present in the foods.
Foods with medicinal components required for human health promotion and disease prevention, in addition to their nutritional significance, can be regarded as functional foods. These foods may have health-promoting and disease-preventing effects against several chronic diseases and disorders. Several agricultural and industrial residues represent a great alternative as the raw material of bioactive compound production and have been reported to be sources of potentially safe natural additives with different biological activities for the food industry. Furthermore, plant extracts containing bioactive compounds can be used as functional food ingredients and for the production of drugs in the food and pharmaceutical industries. In recent times, more than 80% of functional food bioactive compounds and more than 30% of drugs were produced from bioactive natural products. The bioactive compounds are produced as secondary metabolites, which are substances that have bioactivity in cells and different organs of the body and are referred to as phytochemicals. Plant extracts containing bioactive compounds can be used as functional food ingredients or for the production of drugs for the treatment and/or management of various degenerative diseases.
Diabetes mellitus is a chronic metabolic disease associated with an increase in blood glucose that is due to insufficient or inefficient insulin secretion, with alterations in carbohydrate, protein, and lipid metabolism. Type-2 diabetes is the non-insulin-dependent type of diabetes and the most common form of this chronic disease. Studies have shown that only 10% of people who have diabetes mellitus have insulin-dependent diabetes, which is also known as type-1 diabetes. Hyperglycemia is caused by defects or alterations in either the secretion or action of insulin. Previous reports have shown that increased oxidative stress plays a major role in the early onset and progression of diabetes.
Oxidative stress could occur via peroxidation of cellular organelles, ß-cell apoptotic pathways activation oxidative damage to pancreatic ß-cells since the pancreas has been known to be susceptible to free radical attack due to its low antioxidant capacity.
B-cell dysfunction can also be induced by long-term exposure to high levels of glucose, free fatty acids, or a combination of both. In diabetic conditions, low levels of glucose in the muscle and adipose tissue can cause extracellular hyperglycemia, which can lead to tissue damage and diabetic complications such as heart disease, atherosclerosis cataract formation. neurodegenerative diseases, and diabetic retinopathy. In this same condition, hyperglycemia can cause the development of diabetic complications by stimulating the generation of free radicals via different pathways and mechanisms involving oxidative phosphorylation, glucose autooxidation, NAD(P)H oxidase, lipooxygenase, cytochrome P450 monooxygenases, and nitric oxide synthase (NOS). It is worthy to note that the different pathways leading to the incidence and pathogenesis of diabetes mellitus could represent therapeutic targets for functional food bioactive compounds. A good approach to reduce postprandial hyperglycemia involves the prevention of carbohydrate absorption after a meal.
Enzymes such as a-amylase and a-glucosidase catalyze the breakdown of complex polysaccharides and oligosaccharides into glucose, which is absorbed into the intestinal epithelium and finally goes into blood circulation. Inhibition of these enzymes by plant phenolics will delay the absorption of glucose in the blood and reduce postprandial hyperglycemia. Some phenolic compounds from plant foods and food-related products have been reported to be good inhibitors of a-amylase and a-glucosidase activities, Numerous studies have shown that polyphenols are potent natural inhibitors of a-amylase and a-glucosidase activity.
Furthermore, plant foods and food-related products such as bitter leaf (Vernonia amygdalina Del), Ethiopian pepper (Xylopia acthiopica), calabash nutmeg (Monodora myristica), clove bud (Syzygium aromaticum), black pepper (Piper guineense), bastered melegueta (Aframomum danielli), and alligator pepper (Aframomum melegueta), ginger (Zingiber officinale), shaddock fruit and peels (Citrus maxima), etc. have been reported to have strong antidiabetic activity. The antidiabetic properties of some of these plant foods were reported to be associated with their phenolic constituents as well as other bioactive components that may have synergistically or additively interacted to elicit the observed biological effects.
Role of flavonoids in Diabetes
Flavonols and their glycosides are potent glucosidase inhibitors. The structure-activity relationship has shown that flavonoids with more hydroxyl groups have higher inhibitory effects on a-amylase activity attributed to the inhibitory effects of quercetin, daidzein, and myricetin on a-amylase activity to the number of hydroxyl groups on the B ring and the formation of hydrogen bonds between these hydroxyl groups and amino acid residues on the active site of the enzyme. Some reports have also revealed that phenolic compounds with unsaturated 2,3-bond in conjugation with a 4 carbonyl group have been associated with stronger enzyme inhibition. In addition, galloylated catechin derivatives, catechol-type catechin derivatives, catechin derivatives with 2,3-trans structure, and ellagitannins with ß-galloyl groups at glucose C-1 positions have displayed high inhibitory effects on a-amylase activity, Green tea has been reported to be rich in catechin and its derivatives, which are potential antidiabetic agents. Interestingly, cyanidin and its glycosides can inhibit pancreatic a-amylase and intestinal a-glucosidase activity. The structure-activity relationship revealed that the presence of glucose moiety at the 3-0-position of cyanidin markedly increased the inhibition of pancreatic α-amylase.
Other flavonoids such as xanthones, quercetin, genistein, apigenin, luteolin, isoquercitrin, and vitevin isorhamnetin-3-0-rutinoside have been shown to have high a-glucosidase inhibitory activity. In addition, in silico docking analysis has shown that quercetin, myricetin, and rutin have stronger a-glucosidase activities than acarbose.
Phenolic acids such as gallic, caffeic, chlorogenic, and rosmarinic acids have been shown to have strong a-glucosidase inhibitory activity in vitro and in vivo. However, the inhibitory effects of these phenolic acids were lower than that of acarbose. Furthermore, sarcoidosis and sacrcoviolins isolated from the edible mushroom Sarcodon leucopus showed strong a-glucosidase activity. Their inhibitory activities were attributed to the number of hydroxyl groups present in the structure. These hydroxyl groups have been shown to contribute immensely to the inhibition of the enzyme. In addition, antidiabetic activity of stilbene dimmers such as cassigarol, scirpusin, and scirpusin that were isolated from the rhizomes of Cyperus rotundus L. (Cyperaceae) have been investigated.
Role of alkaloids in Diabetes
The enzyme inhibitory effects of some alkaloids have been reported and documented in the literature. Piper umbellactam B and piperumbellactam C isolated from branches of Piper umbellatum showed moderate a-glucosidase inhibitory activity, while vasicine and vasicinol have been shown to have high sucrase activity. Moreover, the maltase inhibitory activity of 3,4 dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid have been attributed to the number of caffeoyl groups on the structure. It has been reported that conophylline, a vinca alkaloid from Ervatamia microphylla, decreased blood glucose level and increased plasma insulin level in streptozotocin-induced diabetic rats by inducing the differentiation of pancreatic precursor cells to insulin-producing cells. Oxidative stress via free radical generation has also been implicated in the development of diabetic complications, insulin resistance, and ß-cell dysfunction. The islet B-cells are susceptible to oxidative damage by reactive oxygen species (ROS) due to low antioxidant enzymes, which can lead to dysregulation of insulin secretion. Dysregulation of insulin secretion could also be influenced by protein tyrosine phosphatase-1B (PTP-1B), a negative regulator of the insulin signaling pathway that has been implicated in the progression of diabetes mellitus. Some alkaloids such as Gwendoline, vindolidine, vindolicine, and vindolinine have been reported to inhibit PTP-1B, thereby ameliorating insulin resistance and enhancing cellular glucose uptake activity. The hypoglycemic activity of catharantine, vindoline, vindolinine, and arecoline has also been reported. Similarly, trigonelline and 4-hydroxy isoleucine isolated from Trigonella foenumgraecum seeds have been reported to show hypoglycemic activity in alloxan-induced diabetic rats. These two compounds showed a glucose-lowering effect in hyperglycemic conditions. Moreover, oral administration of 4-hydroxy isoleucine to alloxan-induced diabetic rats brought about the regeneration of beta cells in the pancreas compared to the control rats, which had damaged cells. Previous work on natural antidiabetic agents has shown that ß-carboline alkaloids have antihyperglycemic activity. Harmane, norharmane, and pinoline, which are members of the ß-carbolines, are capable of increasing insulin secretion in human islets of Langerhans.
Role of Triterpenoids Steroids in Diabetes
Triterpenoids are known to be potent antihyperglycemic agents. Many studies have revealed the antidiabetic activity of triterpenoids and their glycosides. The hypoglycemic effects of triterpenoids. and their glycosides such as 5-3,19-epoxy-3-3.25-dihydroxycucurbita 6,23-(E)-diene,3-3,7-8,25 trihydroxycucurbita-5,23-(E)-dien-19-al.3b-Acetoxy-16b-hydroxybetulinicacid, betavulgaroside, and boussingoside have also been reported. The hypoglycemic effect of steroidal glycosides pseudoprototimosaponin and prototimosaponin isolated from the rhizomes of Anemarrhena asphodeloide in streptozotocin-induced diabetic rats was linked to the inhibition of gluconeogenesis and/or glycogenolysis. Charantin, a steroidal saponin present in Momordica charantia, elicited its antidiabetic effects by inducing the release of insulin and inhibiting the absorption of glucose in the bloodstream.
The inhibition of aldose reductase is another relevant therapeutic approach for the management of diabetes. Aldoreductase catalyzes the reduction of glucose to sorbitol via the polyol pathway. Hyperglycemia may influence high levels of glucose into the polyol pathway, thereby leading to the accumulation of sorbitol.
Moreover, the accumulation of sorbitol has been implicated in the development of diabetic complications such as neuropathy, nephropathy, retinopathy, and cardiovascular diseases. Some natural bioactive compounds are potent inhibitors of aldose reductase. Over the years, flavonoids and their derivatives have gained the interest of researchers as aldose reductase inhibitors. Recent reports have revealed that the hydroxylation, glycosylation, and hydrogenation of the C2 =C3 double bond in the flavonoid structure are responsible for their inhibitory effects on aldose reductase activity. Polyphenolic compounds from green tea leaves are also potent inhibitors of aldose reductase. The major polyphenols in green tea are epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG), and gallocatechin gallate (GCG). The higher inhibitory effects were attributed to the glycosylation of the catechins. Phenolic compounds such as hispidin, hispolon, and inotilone isolated from ethanol extract of Phellinus merrillii are also strong inhibitors of aldose reductase. Phenolic acids such as caffeic acid, chlorogenic acid, gallic acid, and caffeoylquinic acid, and p-coumaric acids identified in coffee beans have been reported to be potent inhibitors of aldose reductase. In another study, gallic acid and protocatechuic, p-hydroxybenzoic, p-coumaric, vanillic, syringic, ferulic, and trans-cinnamic acids from Eleusine coracana were shown to inhibit aldose reductase activity. The inhibitory effects of Paulownia coreana seeds on aldose reductase activity have also been reported. The inhibitory effects were attributed to phenylpropanoids such as verbascoside, is verbascoside, and isocampneoside, which were identified in the seeds. Polydatin, resveratrol, and its derivatives, naturally known as stilbenes, are important polyphenols present in plant foods that are also potent aldose reductase inhibitors.
Cardiovascular disease (CVD) is a complex and multifactorial disease and is characterized by multiple factors. Epidemiological studies have shown that the prevalence of CVD is on the increase. CVD is the major cause of death in both developing and developed countries. It is characterized by different risk factors such as family history, ethnicity, age, unhealthy diets, high blood pressure (BI), obesity, type 2 diabetes (T2D), elevated serum lipids (cholesterol and triglycerides), increased plasma fibrinogen, and coagulation factors, increased platelet activation, alterations in glucose metabolism, smoking, and oxidative stress. On the other hand, hypertension is a common cardiovascular disease that has become a worldwide problem.
However, there are limited comparable data on the global prevalence of hypertension; the estimated prevalence of hypertension in different European countries appears to be about 30% 45% of the general population, with a gradual increase with age. The renin-angiotensin system (RAS) is another important enzyme involved in the regulation of blood pressure, water and salt balance, and pathophysiology of cardiovascular and renal diseases. Angiotensin I, released from angiotensinogen by renin, is acted upon by angiotensin I converting enzyme (ACE) to produce a potent vasoconstrictor, angiotensin II. Thus, ACE inhibition is regarded as a vital therapeutic strategy in the treatment and management of hypertension in both diabetic and nondiabetic patients. The renin-angiotensin-aldosterone system (RAAS) is a hormonal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders. Renin activates the release of angiotensin I from angiotensinogen, which is subsequently cleaved by ACE for the production of angiotensin II (a potent vasoconstrictor). ACE inhibitors (ACEIs) competitively block the action of ACE and thus the conversion of angiotensin I (Ang D to angiotensin II (Ang II, thereby reducing circulating and local levels of Ang II ACEL, also decrease aldosterone and vasopressin secretion and sympathetic nerve activity, but there is controversy regarding their efficacy in blocking other “tissue” actions of the RAAS. ACEIs are currently indicated for the treatment of hypertension, diabetic nephropathy, and chronic heart failure, and their use has been associated with improved survival and considerable cardiovascular and renal benefits in high-risk patients. These remarkable benefits have been obtained even though blocking RAAS with currently available agents may be incomplete, raising the possibility that additional therapeutic modalities for RAAS blockade might help to further slow the progression of cardiovascular and renal diseases. Functional foods and food products such as cocoa, coffee, and condiments are beneficial in the prevention and treatment of hypertension and heart-related diseases. Moreover, the therapeutic effects exerted by these functional foods have been attributed to their bioactive constituents Recent investigations show that these bioactive compounds play a beneficial role by normalizing the abnormal lipids, lipoproteins, blood pressure, and inhibition of platelet aggregation, and increasing antioxidant status.
Neurodegenerative diseases are characterized by loss of integrity of the neurons from the brain and spinal cord over some time and could lead to dementia. The aging process originating from excess reactive oxygen species (ROS) production has been attributed to the global increase in neurodegeneration. Theories of aging mechanisms have suggested that cumulative oxidative stress might cause mitochondrial dysfunction and oxidative damage leading to neurodegenerative 3 diseases, characterized by memory impairment and cognitive dysfunction. It is generally accepted that the brain is prone to oxidative stress because of the high level of fatty acids, high oxygen consumption, and low level of antioxidant defense. Cognitive enhancement, also known as intelligence enhancement, could be defined as the amplification of one’s power to learn or retain knowledge by increasing internal or external information processing systems. The brain is an important organ in the body that controls physiological and cognitive functions via interconnections among billions of neurons in the brain to form communication networks. Therefore, regulation of the chemical messengers, known as neurotransmitters, and proper maintenance/control of oxidative stress are major ways of ensuring successful regulation and coordination of body activities. The most common form of dementia is known as Alzheimer’s disease (AD), which is the progressive loss of intellectual and social behavior severe enough to interfere with the daily activities of the patients. The cholinergic hypothesis is the most accepted theory to explain the pathogenesis of AD. Acetylcholinesterase (AChE) is the key enzyme responsible for the breakdown of acetylcholine. Inhibition of AChE is considered one of the targets for the treatment of AD. The most prescribed drugs for the treatment of AD are cholinesterase inhibitors. Acetylcholinesterase (ACE) is an enzyme bound to the membrane and hydrolyzes the neurotransmitter acetylcholine (ACh) into choline and acetate after their function in cholinergic synapses at the brain region.
Hypoinsulinemia (decreased level of insulin in the blood), as well as insulin resistance, account for the decreased level of ACh and provide the possible biochemical link between diabetes mellitus and Alzheimer’s disease. The response of ACE to oxidative insults may lead to the incidence and pathogenesis of a variety of central nervous system disorders, such as stroke, Alzheimer’s disease, and diabetes mellitus. Our investigation on the possible effect of protocatechuic acid revealed that protocatechuic acid altered Na+/K+-ATPase, cholinergic, and antioxidant enzyme activity in rats We also reported that alkaloid extracts from shea butter and breadfruits were able to inhibit monoamine oxidase, cholinesterase, and lipid peroxidation in an in vitro model.
Endothelial dysfunction is one of the biomarkers that contribute to the pathogenesis and clinical expression of cardiovascular diseases such as atherosclerosis, myocardial infarction, and erectile dysfunction. The vascular endothelium plays a key role in the regulation of vascular homeostasis by releasing factors that act locally in the vessel wall and lumen, preventing adherence of leukocytes and inhibiting the expression of adhesion molecules at the endothelial surface. Endothelium-derived nitric oxide modulates vascular homeostasis, acts as a potent vasodilator in the endothelial tissues, prevents lesion formation and hypertrophy of the vessel wall, and exhibits anti-inflammatory, antithrombotic, and growth-suppressing properties: This shows that loss of nitric oxide (NO) due to changes in the regulatory mechanism can lead to endothelial dysfunction Furthermore, some reports have suggested that other pathological conditions such as dyslipidemia, hypertension, diabetes mellitus, oxidative stress, aging, systemic inflammation, hyperhomocysteinemia, and infectious processes can also contribute to endothelial dysfunction Other risk factors that influence endothelial dysfunction include dietary, genetic, and environmental factors. However, improving endothelial function can alleviate some effects caused by CVDs. Some investigations also revealed that phenolic beverages can reverse endothelial dysfunction. Flow-mediated dilation improves NO production in the endothelium. Impairment of this physiological response could pose a great risk to coronary heart diseases. Moreover, impaired physiological responses in the brachial artery could lead to the onset of cardiovascular events in high- and low-risk patients. Meanwhile, consumption of tea has been linked to the production and improvement of NO bioactivity. Green tea contains bioactive compounds such as quercetin rutin kaempferol, catechins which have been reported to be responsible for its bioactivity.
Furthermore, flavonoid-containing beverages from grape juice also improved endothelial function and brachial artery-mediated dilation in patients with coronary artery disease. Beverages made with cocoa are rich in procyanidin and can reverse endothelial dysfunction. Phenolics from olive oil and nuts can act on inflammation and endothelial dysfunction, thereby preventing plaque formation and reducing the risk of atherosclerosis. An increase in vasoconstriction and a decrease in vasodilators will lead to a decrease in endothelial-derived NO and endothelial dysfunction. However, bioactive compounds with vasodilatory properties will prevent or reverse endothelial dysfunction. Some polyphenols have been reported to possess vasodilatory properties. Phenolics from red wine (quercetin, resveratrol, and delphinidin) can activate the enzyme involved in NO production and improve endothelial function. These findings corroborate that dietary interventions could reduce CVDS and improve endothelial function via different mechanisms such as NO production, lipid-lowering effects, inhibition of angiotensin-1 converting enzyme. angiotensin receptor blockers, and mediation of anti-inflammation.
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