Bioactive Polyphenols and Carotenoids PDF

Bioactive Polyphenols and Carotenoids Dr. Zaheer Ahmad Outline Introduction Structure-Function Considerations Specific Polyphenols Products Carotenoids 2  Introduction Polyphenolic compounds are widespread in various food plants and are a...

Bioactive Polyphenols and Carotenoids Dr. Zaheer Ahmad Outline Introduction Structure-Function Considerations Specific Polyphenols Products Carotenoids 2  Introduction Polyphenolic compounds are widespread in various food plants and are a significant component of the human diet. Traditionally, polyphenols were considered to have adverse effects on health due to their ability to bind and reduce the bioavailability of nutrients like minerals, proteins, and carbohydrates. However, recent research highlights the potential health benefits of certain polyphenols as antioxidants and free radical scavengers. These benefits include their role in: 9/8/20XX PRESENTATION TITLE 3  Introduction continue… Polyphenols can enhance antioxidant enzyme levels such as NADPH-quinone oxidoreductase, glutathione S-transferase, cytochrome P450, glutathione peroxidase, and catalase, which increases capacity of the body to detoxify carcinogens Polyphenols downregulate the p38/CREB signaling and inhibit protein phosphorylation (blocks cell cycle progression) and COX-2 expression to attenuate cancer cell growth. 9/8/20XX 4 1. Anticancer Activity: Polyphenols act against cancer by removing carcinogenic agents, modulating cancer cell signaling and cell cycle progression, inducing various enzyme activities, and promoting apoptosis (programmed cell death). They enhance the body's capacity to detoxify carcinogens. 2. Cardiovascular Health: Polyphenols can improve blood circulation by reducing plasma cholesterol and free fatty acids, potentially reducing the risk of cardiovascular diseases. 3. Protection Against Oxidative Stress: Polyphenol-rich extracts, such as those from blackberries, can protect against oxidative stress by increasing the activity of antioxidant enzymes like catalase, glutathione peroxidase, and superoxide dismutase. 5 4. Preventing Advanced Glycation End Products (AGEs): Polyphenolic extracts from berries and grapes can scavenge carbonyl compounds implicated in the production of AGEs, which are linked to chronic diseases like diabetes and aging. 5. Atherosclerosis Prevention: Anthocyanin-rich mulberry extracts can prevent atherosclerosis by increasing apoptosis, reducing hepatic lipid accumulation, and improving lipid metabolism. 6. Vasodilation and Blood Pressure Regulation: Catechins from oil palm leaves have vasodilatory properties, lower blood pressure, and act as antioxidants, protecting various organs from injury. 7. Cognitive Function: Blackberry polyphenols have been associated with improved memory scores, potentially due to their antioxidant properties. 6  Plant polyphenols vary in molecular structure, some soluble and others non-extractable but highly potent antioxidants. While non-extractable polyphenols are less readily absorbed, they protect nutrients during digestion. Soluble polyphenols are absorbed and transported to organs and tissues, exerting physiological benefits. The health benefits of polyphenols primarily stem from their antioxidant properties, which involve donating protons to free radicals and acting as antioxidants in the body. However, in certain conditions, such as high concentrations, high pH, and the presence of iron, polyphenols can act as prooxidants by initiating free radical formation. 7 Structure- Function Consideration s Structur e: - Their chemical structure determines the antioxidant efficiency of polyphenols, as phenol alone does not possess antioxidant properties. - Diphenols in the ortho- and para-forms exhibit antioxidant activity, further enhanced when hydrogen atoms on the aromatic rings are substituted by ethyl or n-butyl groups. - Certain structural characteristics are known to enhance the antioxidant properties of flavonoids, including: 1. The presence of an o-diphenolic group in the B ring. 2. A 4-oxo function that is in conjugation with a 2,3 double bond. 3. Hydroxyl (OH) groups in the 3rd and 5th positions. 9 10 11 12 13  Function s:  Flavonols like quercetin are potent natural antioxidants because they possess all three of the above-mentioned structural characteristics.  The number of OH groups in flavonoids correlates directly with their antioxidant efficiency. However, attached sugar molecules (glycosides) negatively affect antioxidant activity.  Glycosides generally have little or no antioxidant activity but upon hydrolysis by b- glycosidases, the resulting in aglycones exhibiting antioxidant properties.  Consumption of prebiotics can increase the glycolytic capacity of colon microflora, leading to enhanced conversion of glycosidic polyphenolic compounds into aglycone forms.  Increased microflora activity can also promote the metabolism of complex polyphenols into more simpler and more readily bioavailable breakdown products.  Simultaneously administering prebiotics and polyphenols in the diet may enhance the biological effects of polyphenolic compounds through these mechanisms. 15  Function s:  Flavonols like quercetin are potent natural antioxidants because they possess all three of the above-mentioned structural characteristics.  The number of OH groups in flavonoids correlates directly with their antioxidant efficiency. However, attached sugar molecules (glycosides) negatively affect antioxidant activity.  Glycosides generally have little or no antioxidant activity but upon hydrolysis by b- glycosidases, the resulting in aglycones exhibiting antioxidant properties.  Consumption of prebiotics can increase the glycolytic capacity of colon microflora, leading to enhanced conversion of glycosidic polyphenolic compounds into aglycone forms.  Increased microflora activity can also promote the metabolism of complex polyphenols into more simpler and more readily bioavailable breakdown products.  Simultaneously administering prebiotics and polyphenols in the diet may enhance the biological effects of polyphenolic compounds through these mechanisms. 16 Specific Phenolic Products Grape and Red Wine Polyphenol Extracts Red wine polyphenolic extract (RWPE) acts as an antioxidant and can reduce superoxide anion levels in animal tissues, making it a potential therapeutic tool for treating and preventing endothelial dysfunction. High tissue reactive oxygen species (ROS) levels, like superoxide anion, can potentiate cardiac hypertrophy. RWPE consumption can significantly reduce cardiac hypertrophy associated with fructose-fed rats.  RWPE exhibits vasorelaxing properties, which contributes to its antihypertensive effects. Red wine polyphenols can increase the nitric oxide-cyclic GMP pathway in vascular tissues. Red wine polyphenols have a better affinity for binding with omega-3 fatty acids than omega-6 fatty acids. This protects omega-3 fatty acids from the damaging effects of ROS, potentially increasing anti-inflammatory eicosanoids in the blood and reducing the risk of atherosclerosis. Various polyphenolics in food products can increase health benefits through synergistic effects. For example, a fruit juice mixture containing juices from various fruits showed significantly higher antioxidant power than single polyphenol compounds, protecting cells against lipid oxidation and damage. Lipophilic polyphenols can enter cells or become localized in lipid compartments to exert beneficial effects. These polyphenols prevent the rapid cellular utilization of glutathione, thus contributing to long-term antioxidant status and cell stability against endogenous free radicals and peroxides. Red grape skin polyphenolic extract enriched in anthocyanins can prevent hypertension, cardiac hypertrophy, and ROS formation in a high-fructose diet. 19  Procyanidin B2 (PB2), a flavonoid found in red grape juice, cocoa, and red wine, protects against oxidative stress-related intestinal injury and gut pathologies. It enhances the expression of antioxidant enzymes and nuclear factor, contributing to cellular antioxidant and detoxification capacities. PB2 activates cellular kinases such as extracellular signal- regulated protein kinases (ERKs) and p38 MAPK, improving antioxidant defenses and protecting against oxidative injury. PB2 treatment can protect cells against oxidative damage and cell death induced by peroxide, making it a promising compound for preventing oxidative stress-related health issues. 20  Resveratrol Resveratrol is a non-flavonoid polyphenolic compound in dark-colored grapes, wine, and grape juice. Resveratrol is an inhibitor of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), which are overexpressed in colon cancer. It also inhibits monoamine oxidase, promotes protease degradation of Aβ (associated with Alzheimer's disease), and acts as an antioxidant. Resveratrol has been shown to induce angiogenesis and neurogenesis in the hippocampus, leading to improved spatial learning and potential benefits in Alzheimer's disease and cognitive functions. 21  Resveratrol inhibits cell proliferation and induces apoptosis in various cancer cells, potentially preventing colon, mammary, and skin cancers. It may also inhibit prostate cancer by inhibiting androgen-stimulated cell growth. Resveratrol has cardiovascular benefits, including increased blood flow, decreased inflammation, and reduced oxidative stress. It upregulates endothelial nitric oxide synthase (eNOS), leading to enhanced nitric oxide-mediated vasodilation. Resveratrol may help ameliorate diet-induced obesity, improve glucose metabolism, and act as an antidiabetic agent by reducing blood glucose levels, improving insulin sensitivity, and inhibiting fatty acid synthesis. The compound's ability to inhibit fatty acid and triglyceride synthesis, increase glucose uptake, promote mitochondrial biogenesis, and suppress lipid accumulation in adipose tissue contributes to its anti-obesity effects. 22  Apple polyphenols Apple polyphenols, especially flavonoids, are believed to offer various health benefits. While there is no definitive data from human studies, several animal and cell culture experiments suggest that apple consumption may reduce the risk of chronic diseases. Apples are rich in polyphenolic compounds, surpassing the combined contents of vitamin C, magnesium, and calcium. The skin of apples contains higher levels of polyphenols, including some anthocyanins, compared to the fruit tissue. Flavonoids in apples can act as antioxidants, spare vitamin C, reduce inflammation, inhibit cell proliferation, and prevent blood clot formation. Quercetin, a polyphenol found in apples, protects against oxidative stress- induced neurodegeneration and may be beneficial in conditions like Alzheimer's. 23  Apple polyphenols Apple polyphenols have been shown to reduce markers of carcinogenesis and enhance the vascular system. They have effectively reduced cell growth and proliferation in liver cancer cells and prevented mammary cancer development in experimental rats. Within the gastrointestinal tract, apple polyphenols have direct effects, such as iron sequestration and scavenging of reactive nitrogen, oxygen, and chlorine species. They also exhibit antioxidant effects, reducing lipid peroxidation associated with high dietary cholesterol. Some studies suggest that the increase in human plasma antioxidant activity attributed to apple consumption may be related to fructose-induced formation of urate, an important physiological antioxidant. It is recommended to consume whole apples, including the skin, to maximize the health benefits of polyphenols and other bioactive compounds found in apples. 24  Lychee fruit Polyphenol Lychee fruit, native to Southern China and Southeast Asia, has a pink-red outer skin rich in polyphenols. A polyphenolic-rich product called Oligonol has been developed from lychee fruits.. Oligonol's polyphenolic compounds have shown high bioavailability, which enhances their physiological effects. In vitro tests have demonstrated that Oligonol inhibits the activity of xanthine oxidase in a dose-dependent manner. Xanthine oxidase is an enzyme involved in the synthesis of uric acid. Human experiments have shown that consumption of Oligonol results in significant reductions in serum and urine uric acid levels, indicating a decrease in uric acid synthesis due to the inhibition of xanthine oxidase activity. Oligonol's polyphenols may have potential applications in reducing the risk of hyperuricemia (high uric acid levels) and gout.  Curcumin - Curcumin exhibits various biological activities, including chemopreventive, anticancer, antiangiogenesis, anti-inflammatory, antioxidant, and chemotherapeutic properties. - Most studies on the effects of curcumin on obesity have been conducted in animal experiments, particularly in mice and rats. - When curcumin was added to a rat diet, it increased bile acid excretion and reduced liver cholesterol, liver weight, plasma free fatty acids, plasma triglycerides, and total body weight. - Curcumin can reduce angiogenesis, essential for the growth of adipose tissues and cancerous tumors. It achieves this by downregulating key cellular factors involved in angiogenesis, such as VEGF, bFGF, EGF, angiopoietin, and HIF-1α. - Curcumin enhances the activation of AMPK while reducing ACC activity, leading to increased mitochondrial oxidation of long- chain fatty acids. This contributes to reduced fatty liver formation, decreased fatty acid and cholesterol synthesis, and increased hepatic β-oxidation. - Curcumin can attenuate the progression of type 2 diabetes and liver inflammation by reducing the expression of NF-κB and inhibiting the migration of macrophages into adipose tissue. - Curcumin also suppresses the expression of key transcription factors involved in adipogenesis and lipogenesis, such as PPARγ and C/EBPα, thereby inhibiting the differentiation of preadipocytes into adipocytes and slowing the growth of adipose tissue. 26  Phytoster ols Phytosterols are plant compounds with a similar chemical structure to cholesterol but are found exclusively in plant-based foods like vegetables, fruits, seeds, and vegetable oils. There are two primary forms of phytosterols: sterols and stanols. Sterols have an unsaturated aromatic ring structure, while stanols are the saturated forms. They have several health-related effects: 1. Cholesterol Reduction: Phytosterols are known for reducing cholesterol absorption from the intestinal tract. They compete with cholesterol for absorption and can induce cholesterol precipitation, limiting its absorption. This cholesterol-lowering effect is particularly effective when phytosterols are consumed as part of an edible fat or oil. 2. Food Fortification: Fortifying margarine with phytosterols has been a popular way to create cholesterol-lowering functional foods. Human trials have shown that combining cholesterol-lowering drugs with phytosterol-fortified margarine can result in an additional 10–20% reduction in LDL cholesterol levels. 27 3. Cardiovascular Health: Phytosterol-fortified beverages and milk have been shown to reduce serum cholesterol levels by up to 8% and 12%, respectively, in hypercholesterolemic and healthy individuals. Phytosterols have a similar cholesterol-lowering benefit in both groups. 4. Safe Consumption: Phytosterols are generally safe for consumption, even at high doses. Studies have not reported adverse side effects like memory impairment or anxiety- related behavior. 5. Mechanism of Action: Phytosterols limit cholesterol absorption and decrease cholesterol esterification within enterocytes. 6. Effects on Atherosclerosis: Phytosterols have been shown to reduce the size and complexity of atherosclerotic plaques in animal studies. 28 7. Absorption of Fat-Soluble Antioxidants: Consumption of plant stanols can reduce the absorption of lipophilic hydrocarbon carotenoids (e.g., β-carotene, lycopene, lutein) and tocopherols (vitamin E) due to their interference with incorporation into mixed micelles. 8. Membrane Integrity: There is some concern that regular consumption of phytosterols might affect the integrity of cell membranes, potentially leading to increased fragility and stiffness in red blood cell membranes. However, these effects have primarily been observed in animal studies. 9. Platelet Aggregation: Phytosterols, when consumed as part of a diet or margarine, can influence platelet adhesion and aggregation, which may help prevent the formation of vascular blood clots. 29  Proanthocyanidins Proanthocyanidins (PAs) are a type of polyphenol found in various fruits and vegetables, including grapes, cherries, plums, blueberries, and cranberries. These compounds contribute to the vibrant colors of these foods and have been studied for their potential health benefits. Here are some critical points about proanthocyanidins: 1. Chemical Structure: PAs are high molecular weight forms of epicatechin, one of the most abundant plant polyphenols. They are soluble in aqueous solutions and can yield anthocyanidins when heated in acidic media. 2. Types of PAs: PAs found in cranberries, for example, come in various types with different linkages between epicatechin units. The size of PAs increases as the plant or seed ages, with older plants containing larger, insoluble polymers. 30 3. Absorption: Studies have shown that monomers, dimers, and trimers of PAs are well-absorbed in the gastrointestinal tract, while larger polymers are less efficiently absorbed. Colon microflora can ferment these polymeric PAs into low molecular weight phenols, which may be absorbed. 4. Health Benefits: Antitumor Effects: Some PAs, such as those from grape seeds, have been studied for their potential to limit the intensity of cancer. They may stimulate the immune system, inhibit digestive enzymes, and prevent tumor growth through various mechanisms. However, their therapeutic role in cancer treatment still requires further investigation. Reduced Food Digestion: PAs can inhibit digestive enzymes, reducing nutrient digestion and potentially contributing to reduced caloric intake. This property might have benefits for weight management and blood glucose control. Urinary Tract Infection Prevention: Cranberry PAs are known for preventing urinary tract infections (UTIs). They do this by preventing bacterial adhesion to the urinary tract lining. PAs interfere with the attachment of E. coli bacteria to the urinary tract walls, helping to reduce UTI incidence. 31 Oral Health: Cranberry PAs and other components can help prevent dental caries and maintain oral health by reducing the hydrophobicity of bacterial cells, inhibiting polysaccharide synthesis, reducing glucan binding, and decreasing acid production by cariogenic bacteria. Additionally, they may prevent periodontal diseases by inhibiting the adherence of periodontitis pathogens, inhibiting proteases, and reducing host-mediated proinflammatory responses. 5.Caveats: PAs have potential health benefits; being aware of some considerations is essential. They can chelate iron and interfere with iron absorption, so individuals with iron deficiency anemia should minimize their consumption. Additionally, high levels of dietary PAs may reduce food digestion and nutrient bioavailability. Overall, proanthocyanidins, especially from sources like cranberries and grape seeds, have shown promise in various health-related applications, including cancer prevention, UTI prevention, and oral health maintenance. However, more research is needed to fully understand their mechanisms of action and therapeutic potential in humans. 32  Plant Anthocyanins Purple corn, rich in anthocyanins and other polyphenolic compounds, has shown promise as a potential chemo-preventive and chemotherapeutic agent. Here are the essential findings and potential health benefits associated with purple corn anthocyanins: 1. Diabetic Nephropathy (DN): Purple corn polyphenolic extracts have been found to ameliorate DN, a condition characterized by renal hardening, interstitial fibrosis, and nephrosclerosis due to diabetes. These polyphenols inhibit the production of connective tissue growth factor (CTGF), contributing to DN fibrosis. They also reduce the secretion of proinflammatory cytokine IL-8, thus attenuating disease progression. 2. Angiogenesis and Cell Proliferation: Purple corn polyphenols inhibit platelet-derived growth factor (PDGF) activity, which plays a role in angiogenesis and cell proliferation. By doing so, they can prevent mesangial hyperplasia-induced glomerulosclerosis. 33 3. Reduced Blood Glucose Levels: In animal studies with diabetic mice, including purple corn polyphenol extract in their diet significantly reduced blood glucose levels and improved glucose tolerance during an oral glucose test. 4. Alleviation of Diabetic Complications: Feeding diabetic mice with a purple corn extract-fortified diet led to reduced plasma levels of glycated hemoglobin, a marker for diabetic complications. It also lowered urinary albumin and creatinine levels, indicating improved kidney function. 5. Glomerular Repair: Purple corn polyphenols increased the expression levels of nephrin and podocin, proteins associated with the renal filtration barrier. This suggests the potential for repairing the damaged renal filtration barrier observed in DN. 6. Antioxidant Effects: Purple corn polyphenols have demonstrated in vivo antioxidant effects in rat-feeding experiments. 34 7. Anti-Obesity Effects: In studies with diet-induced obese mice, purple sweet potato anthocyanin extracts reduced body weight, liver weight, and serum glucose levels. These extracts also reduced hepatic lipid accumulation and decreased the expression of lipogenic enzymes, suggesting potential anti-obesity effects. 8. Promotion of Lipid Catabolism: Anthocyanin treatment increased the expression of adenosine monophosphate- activated protein kinase (AMPK), which decreased the activity of fatty acid synthesis enzymes and increased the activity of enzymes involved in lipid catabolism, favoring the breakdown of fats. Purple corn and purple sweet potato anthocyanins show promise in alleviating diabetic nephropathy, reducing blood glucose levels, preventing diabetic complications, and potentially mitigating obesity-related symptoms. Their antioxidant properties and ability to regulate metabolic processes make them attractive candidates for further research and development as functional foods or nutraceuticals. 35  Pomace Olive Oil Triterpenoids and Polyphenolic Constituents Pomace olive oil, extracted from the residual pomace left after mechanical extraction of virgin olive oil, is rich in triterpenoids such as oleanolic and maslinic acids and alcohols erythrodiol and uvaol. These compounds have various bioactive properties and health benefits: 1. Oleanolic Acid: Oleanolic acid, found in pomace olive oil, is an effective antioxidant. It helps protect LDL (low-density lipoprotein) from oxidative damage and has anti- inflammatory, hepatoprotective (liver-protecting), and antitumoral effects. Additionally, oleanolic acid has vasodilation properties and can act as an antihyperlipidemic (reducing high lipid levels) and diuretic-natriuretic agent, which can be beneficial for preventing hypertension. Therefore, pomace olive oil may serve as a functional food for cardiovascular protection and hypertension prevention. 36 2. Antioxidant Effects: Olive oil polyphenolic extract, which includes compounds like gallic acid and other polyphenols, can reduce free radicals in cells after oxidative stress induction. 3. Phenolic Compounds: Olive oil also contains phenolic compounds like hydroxytyrosol (HTy), tyrosol (Ty), and hydroxytyrosyl acetate (HTyAc), among others. These phenolic compounds have antioxidant properties and are bioavailable in the body. They are transported to the liver, where they exert antioxidant and other biological effects before metabolizing into conjugates for excretion in the urine. 4. Cellular Antioxidant Effects: HTy also reduces oxidative stress by suppressing the peroxide-induced increase in glutathione peroxidase (GPx), reactive oxygen species (ROS) levels, and malondialdehyde, a lipid peroxidation product. These findings suggest that Hty can reduce oxidative stress in cells and may have the potential to prevent chronic degenerative diseases associated with excessive tissue ROS levels. 37  Carotenoids These are phytochemicals abundant in fruits and vegetables, and their increased consumption is associated with several health benefits. The carotenoids as a group consist of over 600 fat-soluble pigments that are responsible for the natural colors (yellow, orange, red) of fruits and vegetables. A major structural feature of carotenoids is the presence of several conjugated double bonds. 38 Lycopen e Lycopene is a major carotenoid responsible for the red color in ripe tomato fruits and several other fruits such as watermelon, pink grapefruit, apricots, pink guava, and papaya. It is a phytochemical with numerous potential health benefits. Here are some key points about lycopene: 1. Bioavailability: Lycopene is not synthesized by the human body, so it must be obtained from dietary sources. Its bioavailability is enhanced when it is present in the cis-configuration and consumed with dietary fats. Cooking or heating tomato products can also increase the availability of cis-lycopene. 2. Antioxidant Properties: Lycopene is a potent antioxidant. It can protect cells from oxidative damage caused by reactive oxygen species and free radicals. This antioxidant activity may contribute to various health benefits. 39 3. Cancer Prevention: While epidemiological studies have shown mixed results regarding lycopene's role in cancer prevention, some research suggests that it may help reduce the risk of certain cancers, especially prostate cancer. Lycopene can interfere with the production of insulin-like growth factor 1 (IGF-1), which is known to stimulate cancer cell growth. It can also inhibit the growth of cancer cells and enhance gap junction communication between cells, preventing tumor growth. 4. Atherosclerosis Prevention: Lycopene has been associated with a reduced risk of atherosclerosis, a condition that contributes to heart disease. It can prevent the oxidative damage of LDL cholesterol, a crucial step in the development of atherosclerosis. Lycopene may also inhibit cholesterol synthesis and reduce the adhesion of molecules to vascular endothelial cells, promoting healthy blood vessel function. 5. Obesity Management: Lycopene may have anti-obesity effects. It can inhibit fatty acid synthesis, reduce lipid droplet size in white adipocytes, and increase thermogenesis in brown adipose tissue (BAT). These actions can help prevent excessive weight gain and fatty liver. 40 6. Diabetes Management: Lycopene has been found to improve endothelial function in diabetic rats, which is important for preventing diabetes- related cardiovascular complications. It can also reduce oxidative stress, lower oxidized LDL levels, and improve blood glucose regulation. 41 Thank you…