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Polyphenols and Its Effect on the Immune System

Authors:
Kanchan Gairola at G. B. Pant University of Agriculture and Technology, Pantnagar
Kanchan Gairola
Shriya Gururani at G. B. Pant University of Agriculture and Technology, Pantnagar
Shriya Gururani
Shiv Kumar Dubey at G. B. Pant University of Agriculture and Technology, Pantnagar
Shiv Kumar Dubey
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Abstract

The mainstay of good health is well functioning and strong immune system which involves interaction between acquired and innate components of the immune system that leads to immune responses. In the recent few years, polyphenols are extensively studied for their immunomodulatory properties to achieve the preferable and desirable effects. Polyphenolic compounds exert many biological activities and are known to considerably affect the efficiency of the immune system either in a positive or in a negative manner by either stimulating or suppressing the immune response; hence, they are regarded as important immunomodulatory agents. As these bioactive leads generally show minimal toxicity and have better efficacy, a lot of scientific studies are focused on their clinical uses. The aim of this chapter is to focus on the adequacy and effect of the plant’s polyphenol, such as tannins, lectins, flavonoids, glycosides, anthocyanins, and other phenolic compounds on the immune system at the molecular level and their mechanism of immunomodulation. Keeping the importance of polyphenols in medicinal field and immunomodulation in the view, this chapter mainly highlights the effect of polyphenol on modulation of the immune system.
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... Polyphenols can help protect immune cells from damage by reducing oxidative stress, maintaining their functionality, and supporting an appropriate immune response. 3. Immunomodulation: Polyphenols can modulate immune responses by regulating the activity and function of immune cells involved in the antiviral defence [83]. They can enhance the phagocytic activity of macrophages and promote the maturation and activation of dendritic cells, leading to improved antigen presentation and activation of adaptive immune responses [43]. ...
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... IL-10, transforming growth factor-beta-1 (TGF-β1), IL-6, and IL-17 are found to be balanced by polyphenols as a result of the regulation of Th17 and Tregs. Additionally, polyphenols block NF-κB activation, which prevents the development of dextran sulfate sodium-induced colitis [114]. A graphical representation of the roles of polyphenols in protecting gut health is shown in Figure 2. les 2024, 14, x FOR PEER REVIEW 10 of 19 Figure 2. Polyphenols enhance the well-being of the digestive system by promoting a healthy community of beneficial bacteria and preserving an equilibrium between Th17 and Treg. ...
Polyphenols: Role in Modulating Immune Function and Obesity
Article
Full-text available
  • Feb 2024
Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 75% of the world’s population still use plant-based medicinal compounds, indicating the ongoing significance of phytochemicals for human health. This study emphasizes the growing body of research investigating the anti-adipogenic and anti-obesity functions of polyphenols. The functions of polyphenols, including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids, are distinct due to changes in chemical diversity and structural characteristics. This review methodically investigates the mechanisms by which naturally occurring polyphenols mediate obesity and metabolic function in immunomodulation. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role, in part, in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function and the effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required to understand the prudent and precise mechanisms underlying polyphenols’ therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes a holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.
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... Interleukin-10 (IL-10), transforming growth factor-beta-1 (TGF-β1), interleukin-6 (IL-6), and interleukin-17 (IL-17) are found to be balanced by polyphenols as a result of regulation of Th17 and Tregs. Additionally, polyphenols block NF-κB activation, which prevents the development of dextran sulfate sodium (DSS)-induced colitis (105). A graphical representation of the roles of polyphenols in protecting gut health is shown in Figure 2. ...
Polyphenols: Role in Modulating Immune Function and Obesity
Preprint
Full-text available
  • Jan 2024
Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.
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... Different immune cells express multiple types of polyphenol receptors that recognize and allow cellular uptake of polyphenols, which subsequently activate signaling pathways to initiate immune responses. 20 While the concept of mucosal innate immunity as an early warning system is not new, we believe its full clinical potential is not been realized. Should mucosal immunomodulation with olive polyphenols be able to overcome viral suppression of mucosa innate host defenses, then it can be a useful strategy in this regard. ...
Buccopharyngeal route administered high polyphenolic olive oil and COVID‐19: A pilot clinical trial
Article
Full-text available
  • Oct 2023
Introduction Waning immunity after vaccination justifies the need for additional effective COVID‐19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS‐CoV‐2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID‐19. Summary This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID‐19 incidence, duration, and severity. Importance Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID‐19. Objective Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS‐CoV‐2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID‐19. Design, Setting, and Participants Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID‐19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3‐month study, conducted between July 1, 2021 and August 31, 2022. Intervention Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. Main Outcome and Measures Primary outcomes were incidence, duration, and severity of COVID‐19 after intervention. Results There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no‐treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. Conclusion and Relevance Among full‐vaccinated adults recent infected with COVID‐19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID‐19.
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... 170 Polyphenol is a bioactive substance with high antioxidant activities and antibacterial properties. 171 Feeding of grape seed polyphenols to pigs at a dose of (300 mg/kg) reduced the stillbirths, trum. 173,174 This extract minimizes the inflammatory response by reducing nuclear factor-κB signaling along with activation of the Nrf2/ HO-1 pathway. ...
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Article
Full-text available
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anti-sars-cov-2-activity-chalcones-synthetic-derivatives-salar-hafez-ghoran-fatemeh-taktaz-pouya-alipour-farah-khameis-farag-teia-pascal-douanla-amna-hamad-abdallah-atia
Chapter
  • May 2024
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Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer
Article
Full-text available
  • Apr 2019
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Article
Full-text available
  • Mar 2019
  • INT J MOL SCI
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Article
Full-text available
  • Nov 2018
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The Immunomodulatory and Anti-Inflammatory Role of Polyphenols
Article
Full-text available
  • Nov 2018
This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.
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Polyphenols in the treatment of autoimmune diseases
Article
  • May 2019
  • AUTOIMMUN REV
In addition to protecting body from infections and diseases, the immune system produces auto-antibodies that can cause complex autoimmune disorders, such as Type I diabetes, primary biliary cirrhosis, rheumatoid arthritis, and multiple sclerosis, to name a few. In such cases, the immune system fails to recognize between foreign agents and its own body cells. Different factors, such as genetic factors (CD25, STAT4), epigenetic factors (DNA methylation, histone modifications)and environmental factors (xenobiotics, drugs, hormones)trigger autoimmunity. Glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive and biological agents are currently used to manage autoimmune diseases of different origins. However, complete cure remains elusive. Many dietary and natural products including polyphenols have been widely studied as possible alternative treatment strategies for the management of autoimmune disorders. Polyphenols possess a wide-range of pharmacological and therapeutic properties, including antioxidant and anti-inflammatory activities. As immunomodulatory agents, polyphenols are emerging pharmaceutical tools for management of various autoimmune disorders including vitiligo, ulcerative colitis and multiple sclerosis (MS). Polyphenols activate intracellular pathways such as arachidonic acid dependent pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)signaling pathway, mitogen-activated protein kinases (MAPKs)pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)signaling pathway and epigenetic modulation, which regulate the host's immune response. This timely review discusses putative points of action of polyphenols in autoimmune diseases, characterizing their efficacy and safety as therapeutic agents in managing autoimmune disorders.
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Toll-like Receptors as a Novel Therapeutic Target for Natural Products Against Chronic Diseases
Article
  • Feb 2019
Toll-like receptors (TLR) are one among the initial responders of the immune system which participate in the activation inflammatory processes. Several different types of TLR such as TLR2, TLR4, TLR7 and TLR9 have been identified in various cell types, each having distinct ligands like lipids, lipoproteins, nucleic acids and proteins. Thought its prime concern is xenobiotic defences, TLR signalling has also recognized as an activator of inflammation and associated development of chronic degenerative disorders (CDDs) including obesity, type 2 diabetes mellitus (T2DM), fatty liver disease, cardiovascular and neurodegenerative disorders as well as various types of cancers. Numerous drugs are in use to prevent these disorders, which specifically inhibit different pathways associated with the development of CDDs. Compared to these drug targets, inhibition of TLR, which specifically responsible for the inflammatory insults have proven to be a better drug target. Several natural products have emerged as inhibitors of CDDs, which specifically targets TLR signalling, among these many, are in the clinical trials. This review is intended to summarize the recent progress on TLR association with CDDs and to list possible use of natural products, their combinations and their synthetic derivative in the prevention of TLR-driven CDD development.
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Resveratrol Alleviates Rheumatoid Arthritis via Reducing ROS and Inflammation, Inhibiting MAPK Signaling Pathways, and Suppressing Angiogenesis
Article
  • Dec 2018
Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting joints and is featured by chronic synovial inflammation and angiogenesis. We employed a bovine type-II collagen (BIIC)-induced Sprague-Dawley rat arthritis model and an in vitro RA model based on interleukin (IL)-1β-stimulated rat synovial cells (RSC-364) to explore the preventive effect of resveratrol on RA and the underlying mechanisms. We found that resveratrol ameliorated BIIC-elicited synovitis and RA-related pathological hallmarks such as inflammatory cell infiltration and angiogenesis in the synovial tissue. Also, BIIC-stimulated rats displayed increased serum levels of proinflammatory cytokines and reactive oxygen species (ROS), as manifested by elevated serum malonaldehyde contents combined with reduced superoxide dismutase activity. It is noteworthy that resveratrol abolished BIIC-induced ROS and inflammation, confirming the antioxidative and anti-inflammatory actions of resveratrol in the context of RA. Furthermore, immunoblotting indicated that resveratrol downregulated the increase in the levels of hypoxia-inducible factor-1α (HIF-1α) and that of the activated phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in IL-1β-stimulated RSC-364 cells. Moreover, we observed that resveratrol-treated RSC-364 cells displayed both G0/G1 cell-cycle arrest and enhanced levels of apoptosis. Altogether, the present evidence established the preventive role of resveratrol in RA progression. Mechanistically, resveratrol inhibits MAPK signaling pathways, likely by reducing ROS accumulation, to suppress the inflammatory response and cell proliferation and to provoke cell apoptosis in the synovial tissue, along with mitigation of HIF-1α-mediated angiogenesis. Thus resveratrol appears to hold great potential for clinical translation as a novel RA therapeutic.
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