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Received Aug 29; Accepted Sep Copyright © by the authors. This article has been cited by other articles in PMC. Abstract A balanced metabolic profile is essential for normal human physiological activities.

Disproportions in nutrition give rise to imbalances in metabolism that are associated with aberrant immune function and an elevated risk for inflammatory-associated disorders. Inflammation is a complex process, and numerous mediators affect inflammation-mediated disorders.

The available clinical modalities do not effectively address the underlying diseases but rather relieve the symptoms. Therefore, novel targeted agents have the potential to normalize the metabolic system and, thus, provide meaningful therapy to the underlying disorder.

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In this connection, polyphenols, the well-known and extensively studied phytochemical moieties, were evaluated for their effective role in the restoration of metabolism via various mechanistic signaling pathways. The various flavonoids that we observed in this comprehensive review interfere with the metabolic events that induce inflammation.

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The mechanisms via which the polyphenols, in particular flavonoids, act provide a promising treatment option for inflammatory disorders. However, detailed clinical studies of such molecules are required to decide their clinical fate. Keywords: flavonoids, metabolic disorders, inflammation, oxidative stress, nuclear factor-κB, inflammatory mediators 1.

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In overall summation, the immune system and metabolic pathways are among the primary essentialities, without which the animal kingdom would cease to exist [ 1 ]. Furthermore, both the immune and metabolic pathways co-evolved in a manner in which they are closely linked and interdependent.

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Nutritional imbalances disrupt metabolism, leading to irregular immune function and an elevated risk for inflammatory-associated disorders [ 2 ]. In ancient history, inflammation was characterized based on the visual observations of five cardinal signs specifically named as rubor rednesstumor swellingcalor heatdolor painand lastly function laesa loss of function [ 3 ].

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In short, inflammation could be described as a response of living tissue to local injury [ 45 ]. There is evidence to support that inflammation plays a decisive role in neoplastic progression. This concept is based on the relationship between incessant inflammatory activities due to viruses, bacteria, parasites, infections, and carcinogenesis and their effects within the organs and tissues [ 678910 ].

Inflammation can be further divided into acute and chronic. The local effects of acute inflammation include modifications of metabolic and functional activities of polymorphonuclear cells and macrophages.

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The systemic effects of acute inflammation include modification of immune response and non-specific defenses against infection and neoplasia [ 11 ]. Acute inflammation can also lead to fever and leukocytosis [ 4 ]. Chronic inflammation is characterized by the medical condition of chronic inflammatory disease.

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This medical condition can be defined as a lengthy and persistent pro-inflammatory state marked specifically by the formation of new connective tissue [ 12 ]. There are many diseases included in this category: autoimmune disease, metabolic syndromes, neurodegenerative disease, chronic inflammatory bowel disease, chronic obstructive pulmonary disease, and cardiovascular disease CVD [ 1213 ].

Among the abovementioned diseases and syndromes, metabolic syndromes are strongly associated with chronic inflammation [ 1 ]. These receptors activate major mitogen-activated protein kinase MAPK cascades and stimulate deep 6 pro fat burner recenzii of regulatory nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB [ 7 ]. It was documented that the expression of pro-inflammatory cytokine deep 6 pro fat burner recenzii orchestrates an indispensable role in various CVDs, metabolic syndromes, and atherosclerosis [ 1415161718 ].

A number of investigators reported the natural amelioration of inflammation via the use of polyphenols due to their anti-inflammatory activities [ 192021 ]. It was found that deep 6 pro fat burner recenzii polyphenols, such as flavonoids, are active suppressors of inflammatory cytokines, modulators of transcription factors and inflammation-related pathways, and reducers of accumulated of nitric oxide NO or reactive oxygen species ROS [ 22 ]. Another investigator showed that glabridin also inhibited the maturation of dendritic cells by blocking NF-κB and MAPK signaling cascade [ 27 ].

Research shows that phenolic phytochemicals possess strong antioxidant activity due to the presence of hydroxyl groups within their aromatic rings [ 2930 ].

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The molecular mechanism involved lies in the capacity of the phenolic phytochemicals to increase the level of anti-inflammatory genes, such as glutathione peroxidase GPxsuperoxide dismutase SODand hemeoxygenase-1 HO-1via activation of the nuclear factor erythroid 2-related nhs pierdere gravă în greutate 2 Nrf2 [ 30 ]. To manage metabolic syndromes, global strategies initially focused on lifestyle changes such as diet and physical activity.

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Polyphenols are available in various regular diets, indicating negligible side effects if taken in a controlled manner. This fact makes them a good candidate for their use in various clinical trials in treatment of various diseases.

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There is a large body of evidence to suggest that polyphenols play an effective role as anti-inflammatory agents in various metabolic diseases [ 343536 ]. However, there is no review article that specifically concentrates on this subject.

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In addition, there is little information on the utilization of polyphenols to ameliorate the effect of metabolic disorders, as well as their in vitro and in vivo evaluation. The purpose of this review is to summarize recent data on dietary polyphenols, with a special emphasis on flavonoids, which affect the inflammation involved in various metabolic disorders, and to gather the results of clinical studies on the chronic supplementation of flavonoids on metabolic syndromes features.

Inflammation and Metabolic Disorders Inflammation is a defensive strategy developed in higher organisms in reaction to the harmful effects of tissue injury, microbial infection, and other detrimental conditions.

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It is an important immune response by the host that aids in tissue repair and the elimination of harmful stimuli [ 37 ]. However, long-term inflammation is often harmful and can cause several metabolic diseases [ 13 ] Figure 1.

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