"Functional foods tor immuno-boosting" NYAB Webinar Series - - PDF document

"Functional foods tor immuno-boosting" NYAB Webinar Series Presentation on

18

• Md. Atiar Rahman

• Md. Atiar Rahman PhD, Vice President NYAB

Professor and Chairman, Department of Biochemistry and Molecular Biology University of Chittagong We are available here: https://am-npr.org/ “Functional foods tor immuno-boosting” NYAB Webinar Series Presentation on

19 May 2020

Fu Func nctiona tional l Foo

• ods

ds in a in a brief brief

The term ‘functional food’ was born in Japan in mid-1980s. The Japanese were the first to observe that food could have a role beyond gastronomic pleasure and energy and nutrient supply to the human organism. Following this pioneering, Japan is the country where most functional foods are on the market and the first country to legislate these products in the FOSHU (Foods of Specified Health Use) legislation.Only the products which meet certain requirements can have the FOSHU stamp. Europe and the American countries incorporated later the concept of an added value of food.

Definition and Introduction

The Japanese ‘FOSHU’ criteria for functional food Functional Food in Europe

Approach to Explore

The functional food market has been steadily developing, reaching

• ver $ 21.3 billion in the United States over the past years and
• ver $ 8 billion in Europe.

Knowledge and Expansion

Prebiotics - ingredients or compounds that have a beneficial effect on the microflora in the host itself, such as fiber, fructooligosaccharides, inulin, lactulose, sugar alcohols. Probiotics - living micro-organisms which when ingested in certain amounts, have a positive impact on host health, which goes beyond conventional nutritional effects

Major functions and sources

• f Functional Foods

Lis Listing ting the the functio unctiona nal l foods

• ods us

used ed for

• r dis

diseas eases es

Immu Immunity nity, Immu Immune ne System System and and Immu Immuno no-bo boostin

• sting

Immu Immunit ity y and r rela lated factors

In biology, immunity is the balanced state of multicellular organims having adequate biological defenses to fight infection, disease, or other unwanted biological invasion, while having adequate tolerance to avoid allergy, and autoimmune diseases.

The immune system acts to protect the host from infectious agents that exist in the environment (bacteria, viruses, fungi, parasites) and from other noxious insults. The immune system is constantly active, acting to discriminate ‘non-self’ from ‘self’.

Immuno-boosting

What are you actually boosting? So when something allegedly boosts the immune system, I have to ask what part. How? What is it strengthening/boosting/supporting? Antibodies? Complement? White cells? Are the results from test tubes (often meaningless), animal studies, or human studies? And if in human studies, what was the study population? Are the results even meaningful? Or small, barely statistically significant, outcomes in poorly-done studies? The answer, as we shall see, is usually nothing. If you google the phrase “boost the immune system” you will find over 288,000 pages that give advice on how to give that old immune system a lift. Curiously, a Pubmed search with the same phase yields 1,100 references, most concerning vaccination. If you Pubmed ‘enhanced immune system’ you get 41,000 references mostly concerning

• immunology. None of the references concern taking a normal person

and making the immune system work better than its baseline to prevent or treat infection. I have yet to see a quality clinical study that demonstrates that, in normal, not nutritionally- or otherwise- compromised people, that some intervention can lead to a meaningful increase in immune function and as a result have fewer

• infections. Maybe such a study exists. I can’t find it. Send me the
• reference. I suppose the comment section will soon flood me with

examples. The immune system is your body’s natural defense system. It’s an intricate network of cells, tissues, and organs that band together to defend your body against invaders. Those invaders can include bacteria, viruses, parasites, even a fungus, all with the potential to make us sick.

Integration of Immune response (Calder and Kew, 2002)

Immun Immunob

• balan

alance ce for

• r

imm immuno-boost sting ing

Sou Source ces s of

• f v

varia ariation tion in i in immun mmune e fu func nction tion

(Calder and Kew, 2002)

Mode

• de of
• f Vir

iral al Inf nfection ection

How does Virus infect??

Viruses Commonly causes infections for neonates

How does virus cause damage to host cells??

How do functional foods help attenuate the infections?

Perspective: ROS production and Common functional foods

• The volatile oil (0.4-0.45 %) contains saturated fatty acids which includes:

nigellone that is the only component of the carbonyl fraction of the oil, Thymoquinone (TQ), thymohydroquinone (THQ), dithymoquinone, thymol, carvacrol, α and β-pinene, d-limonene, d-citronellol, p-cymene volatile oil of the seed also contains: p-cymene, carvacrol, t-anethole, 4-terpineol and longifoline (3, 4, 6).

• Black cumin seed have two different forms of alkaloids: isoquinoline alkaloid

that includes: nigellicimine, nigellicimine n-oxide and pyrazol alkaloid that includes: nigellidine and nigellicine (3, 4).

• The study of cinchona bark and its extracts is a key part of the history of

medicinal chemistry as a science – the pure compound was extracted in 1820 by Caventou and Pelletier, and the development of Perkin’s mauve was an attempt by Perkin himself to synthesize quinine. From a chemical standpoint, that work was doomed – no way, no how, was he going to make quinine – but the purple dye he did produce made him wealthy, famous, and kick-started the synthetic dyestuffs industry and industrial organic chemistry in general. Quinine itself wasn’t synthesized until 1944, a wartime effort by Woodward and von Doering, and there has never been a synthesis that can compete with extraction from the bark.

Plant based functional foods: full of antiviral resources Polyphenols

Antibacterial, antifungal and antiviral properties. Fruits and intensely colored plants (blueberries, blackberries, cherries, kiwi, broccoli, spinach, parsley leaves) have antioxidant effects.

Functional Foods in Plants

Feeding fibers (cellulose, pectins, gums, starch) are hydrophilic, draw water in the intestine, gel, increase volume, and regulate intestinal peristalsis. They are found in cereal bran, potatoes, mushrooms, cabbage, carrots, broccoli, pears, apples, quinces,

• bananas. Vegetables

saponins and vitamin A with neurotrophic and neuroprotective

• effect. Cereals (wheat, oats, rye,

rice) act as a lipid antioxidant in the membranes of the immune system cells by the content of vitamin A, E, folic acid, polyphenols, phytoestrogens and their degradation products

Polyphenol Enriched

Production of ROS and scavenging by Functional Foods

Marked signs of increased production

• f

ROS accompany all respiratory viral infections. (Lm et al., 2014).

Ho How the the ROS OS pr prod

• duc

uction tion co could uld be be reso esolv lved ed?

Ncotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases, Nox), Dual oxidase (Duox) and xanthine oxidase (XO). Respiratory viruses also contribute to the production of superoxide anion by Nox2, an enzyme expressed in macrophages and, to a lesser extent, in epithelial cells.

SOD, Catalase, GPx

Antiviral activity of antioxidants and antioxidant enzymes towards respiratory viral infections.

Sources

• f

reactive

• xygen species (ROS) in

airway epithelial cells infected with influenza virus (IV, the left cell)

• r human respiratory

virus (HRSV) and rhinovirus (HRV, the right cell). Cellular events, triggered by ROS production, are detailed in the text.

Curcumin reduces the Nox subtypes

• Fig. Mechanisms of cytokine production (cytokine storm) and epithelial barrier disruption by respiratory viruses. Infection leads

to the enhanced ROS production that may trigger cell death and subsequent macrophage activation. This

activation is accompanied by cytokine production leading to the inflammation and destruction of epithelial cell contacts.

Proinflammatory cytokines could also be produced by infected cells via activation of redox-sensitive nuclear factor kappa B (NFκB) pathway that drives transcription of their genes and via activation of NLRP3 inflammasome in ROS-dependent manner that mediates maturation and secretion of cytokines. Disruption of epithelial barrier results in the increased susceptibility to bacterial infect.

Cytokine production (cytokine storm) and epithelial barrier disruption

Ex Expr pression of ession of CAT T and and S SOD1

Reduces oxidative stress Receptor binding promoted

Conclusion

Number of signaling pathways are upregulated and downregulated Attenuation of PI3K/Akt and NF-κB signaling pathways Targeting cellular transcription Factors affecting cellular post-transcriptional and post- translational modifications

Anti-Inflammatory effects

Wha hat t other

• ther mec

mechanis hanisms ms and and factor actors ar are e rela elated? ted??

Other modes of antiviral action showed by Curcumin

(Ulasli et al., 2014)

Curcumin prevents viral attachment and entry by abrogating the function of viral envelope proteins. Additionally, curcumin modulates the host cell signaling pathways, for instance NF-κB, PI3K-AKT, and inflammation, as well as transcription/translation machineries, which then cardinally hinders the virus replication. Moreover, curcumin serves as a virucidal agent via attacking the integrity of viral envelop. The versatile anti-viral effect of curcumin has been demonstrated in numerous viruses as indicated in the boxes.

Turmeric/ Curcumin: another functional food as antiviral

Immune cell functions affected by vitamins D and E, zinc, n-3 PUFA, probiotics, and EGCG. D, vitamin D; E, vitamin E; Z, zinc; n-3, n-3 PUFA; PB, probiotics; EG, EGCG; , increase; , decrease. Effects of probiotics cited here are for some strains; given the strain-specific nature for the effects of probiotics, these results should not be generalized.

Antiviral Properties of Coconut Oil

There are various functional foods like soya beans, mushroom, coconut

• etc. containing functional bioactive components which have also been

found to help in the reduction of HIV-AIDS complications. Human immunodeficiency virus (HIV) is a retrovirus which causes acquired immunodeficiency syndrome (AIDS). The virus attacks and kills CD4 + lymphocytes, which are essential for initiating an immune response against invading microorganisms (Hummelen 2011). As a result the immune system of the host becomes weaker and gets progressively weaker resulting in failure of immune system thus allowing the

• pportunistic infections such as pneumonia and/or Tuberculosis to thrive.

This virus may take several years to make the infected person ill even if it is present in the person. This condition is called asymptomatic stage. The time taken by HIV virus to express itself or cause disease (AIDS) depend

• n the general health and nutritional status of an individual. By taking

care of their health and good nutrition, HIV infected person can improve the quality of life by reducing the progression of HIV. Nutrition and HIV progression Nutrition and HIV progression are inter-related as the progression of HIV is affected by diet. Malnutrition is common in AIDS patients, and those patients in whom it is more severe tend to die sooner (htt4). HIV infection can lead to malnutrition, while poor diet can in turn speed the infection's progress (Avert Averting HIV and AIDS). So it is very much important to eat the food which enhances immune system and thus reduces HIV progression. The foods which enhance the immune system of an infected person in one way or the other are functional foods. Others found to be beneficial for reducing the HIV progression or boosting immune system is probiotics, prebiotics and micronutrients (Fawzi 2002).

Is t Is there an any y rela lation ionship be ship between the R ROS S production ion and Si Sign gnali aling ng pa pathw hway r ay regu gulation

• n??

??

The key transcription factor that controls expression of an array of defense enzymes is nuclear factor E2-related factor 2 (Nrf2). During normal levels of ROS generation, Nrf2 is retained in the cytoplasm by kelch-like ECH-associated protein 1 (Keap1), which targets Nrf2 to ubiquitin-dependent degradation. When ROS production is enhanced, Nrf2 dissociates from Keap1 and translocates into the nucleus, where it binds the antioxidant response element (ARE) in the promoter regions of target genes encoding predominantly antioxidant enzymes. Noteworthy, the Nrf2 gene itself also contains ARE-like sequences in its promoter. Amongst the Nrf2-regulated target genes are superoxide dismutases, catalase, peroxiredoxins, and glutathione peroxidases. O2 radicals are converted into H2O2 by three SOD isoforms in mammalian cells. Soluble peroxides are eliminated by catalase, peroxiredoxins, and glutathione peroxidases Activation of immune responses during IV infection is achieved partly through Duox2-mediated induction of viral dsRNA sensors RIG-I and MDA5 (retinoic acid- inducible gene I and melanoma differentiation-associated protein 5, respectively) [68,70], pattern recognition receptors that trigger type I IFN responses. IV also enhances production of interferons 1 (IL29), and 2/3 (IL28A/IL28B), again via ROS.

Inhibition of molecular signaling pathways involved in EV-A71 infection by flavonoids. Flavonoids are classified according to their ability at the molecular level to inhibit signaling pathways involved in EV-A71-induced apoptosis, inflammation and infection associated cytokine production. GDP = guanosine diphosphate, GTP = guanosine triphosphate, RAF = rapidly accelerated fibrosarcoma, MEK/MAPK = mitogen-activated protein kinase, ERK = extracellular signal-regulated kinase, SRSF/MnK2a = serine/threonine-protein kinase. JNK = c-Jun N-terminal kinase, ASK = apoptosis signal-regulating kinase, PEG = prostaglandins, COX = cyclooxygenase, and FasL = Fas ligand.

The antiviral activity of flavonoids in the life cycle of EV-A71. Flavonoids are reported to exhibit antiviral activity against EV-A71 and they are categorized according to the mechanism of inhibition at different stages of the virus life cycle. NR: not reported (Flavonoids that affect uncoating, assembly and release of EV-A71 are not reported). HnRNP = heterogeneous nuclear ribonucleoproteins, IRES = internal ribosome entry site, IFN = interferon, JAK = janus kinase, TYK = tyrosine kinase, and STAT = signal transducer and activator of transcription proteins.

Black Seeds, Garlics, Curcumins----------------------------------------------------------------- Omega-3 enriched eggs. Functional Components: Omega-3 fatty acids (DHA); The fatty acid profile

• f the egg yolks is altered by changing the feed the hens receive. Hens receive feed rich in omega-

3s, typically from flaxseed, fish oil or sea algae. The subsequent eggs the hens lay, contain increased amounts of omega-3s, and decreased amounts of saturated fats. What they do: May lower triglycerides, cholesterol, and reduce the risk for coronary heart disease. Foods: Whole eggs in the carton, labeled “DHA/Omega-3-enriched”. Depending on the brand, omega-3 eggs can contain up to 350 mg omega-3s per egg, compared with 60 mg in a regular egg.

• Oats. Functional Components: ß-glucan and phytochemicals called saponins. What they do:

Reduce total and LDL cholesterol, may help lower blood pressure. Foods: Whole oats, oatmeal, lowfat granola, whole-oat bread, other whole-oat products. Fatty fish. Functional Components: Omega-3 fatty acids (DHA and EPA). What they do: Reduce triglycerides, reduce coronary heart disease. Foods: Salmon, Tuna, Striped Bass, Halibut, Sardines, Trout, Flounder. Fortified margarines. Functional Components: Plant Sterol and stanol esters. What they do: Reduce total and LDL cholesterol for those persons with elevated cholesterol. Foods: Fortified margarines such as Benecol, Take Control, and SmartBalance. Replace your normal serving of margarine or butter with fortified margarines. Soy- Functional Components: Phytochemicals such as isoflavones and genistein, and soy protein . What they do: May reduce total and LDL cholesterol. Foods: Edamame, tofu, tempeh, miso, soynuts. Tomatoes and tomato products. Functional Component: The phytochemical lycopene. What they do: The strongest evidence exists for lycopene’s role in the reduction of prostate cancer, but it also may reduce the risk of certain other cancers, and heart disease. Foods: Whole fresh or canned tomatoes, crushed tomatoes, diced tomatoes, tomato paste, tomato soup (low-salt), salsa, gazpacho.

Some common fnctional foods

• Probiotics. Functional Components: “Good for you” bacteria, typically lactobacillus.

What they do: Support gastrointestinal (GI) health, may boost immunity. Foods: Yogurts supplemented with probiotics (look for a variety of live active cultures), fermented vegetables, and fermented soy products (i.e. tempeh).

• Nuts. Functional Components: Monounsaturated fatty acids (healthy fats), vitamin E

(antioxidant). What they do: May reduce the risk of coronary heart disease. Foods: Walnuts, almonds, pecans, pistachios, peanuts, cashews, hazelnuts, chestnuts, and brazil nuts. Grape Juice or Red Wine. Functional Component: Resveratrol. What they do: Exhibit heart-healthy effects. Foods: 100% juice grape juice or grape juice mixtures (i.e. Grape- Apple 100% juice mixtures); any variety of red wine. Leafy Greens. Functional Components: Phytochemicals such as carotenoids, sulforaphanes, apigenin, and lutein/zeaxanthin. What they do: Carotenoids block carcinogens from entering cells (cancer protective), sulforaphanes and apigenin provide heart protection, lutein reduces blindness in the elderly, and zeaxanthin enhances immune function. Foods: Spinach, kale, collard greens, broccoli, broccoli rabe, broccoli sprouts, arugula and other leafy greens.

Take Home Message

❑ Lets increase functional foods in our daily routine ❑ Lets know the Science to explore new options of functional foods ❑ Make an strive to avoid junk Foods

Thanks for your patience hearing