Flavonoids as Potential Anti-Inflammatory Molecules: A Review

Abstract

Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions. Flavonoids such as quercetin, genistein, apigenin, kaempferol, and epigallocatechin 3-gallate modulate the expression and activation of a cytokine such as interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); regulate the gene expression of many pro-inflammatory molecules such s nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and E-selectins; and also inhibits inducible nitric oxide (NO) synthase, cyclooxygenase-2, and lipoxygenase, which are pro-inflammatory enzymes. Understanding the anti-inflammatory action of flavonoids provides better treatment options, including coronavirus disease 2019 (COVID-19)-induced inflammation, inflammatory bowel disease, obstructive pulmonary disorder, arthritis, Alzheimer’s disease, cardiovascular disease, atherosclerosis, and cancer. This review highlights the sources, biochemical activities, and role of flavonoids in enhancing human health.

Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model

“…In the current study, the protein expressions of iNOS and COX-2 generated by DSS were markedly suppressed by treatment with QT-NPs. In this context, administration of phenolic compounds can suppress iNOS and COX2 expression [ 122 , 123 ]. As the activity of flavonoids depends on their absorption and bioavailability in the biological system [ 123 ], the incorporation of flavonoids into nanoparticles could enhance their specificity, stability, bioavailability, and biodistribution and subsequently augment their activities in alleviating IBD [ 124 ].…”

“…In this context, administration of phenolic compounds can suppress iNOS and COX2 expression [ 122 , 123 ]. As the activity of flavonoids depends on their absorption and bioavailability in the biological system [ 123 ], the incorporation of flavonoids into nanoparticles could enhance their specificity, stability, bioavailability, and biodistribution and subsequently augment their activities in alleviating IBD [ 124 ]. Herein, the marked downstream ability of inflammatory mediators such as COX-2 and iNOS was regarded as an advantage of QT-NPs in colitis management.…”

NF-kB (p50/p65)-Mediated Pro-Inflammatory microRNA (miRNA) Signaling in Alzheimer's Disease (AD)

“…These approaches include but are not limited to the following strategies, most of which are under very active research and therapeutic development: (i) antioxidant approaches that neutralize the primary NF-kB activation signals such as quenching of reactive oxygen species (ROS) and other oxidizing and/or redox compounds (Kaur et al, 2015 ; Barnabei et al, 2021 ; Jover-Mengual et al, 2021 ; Pogue and Lukiw, 2021 ); (ii) alteration of multiple phosphorylation events that disrupt the activation of the multi-subunit NF-kB transcription complex and alter the interaction of these phosphorylation sites that ultimately determines the selectivity of NF-κB effects on transcriptional activity (by advanced investigation of these highly interactive phosphorylation sites and mechanisms it should be possible to modulate or block many aspects of phosphorylation-mediated NF-kB activation; Christian et al, 2016 ; https://360researchreports.com/global-nf-kb-inhibitors-market-20149725 ); (iii) as previously pointed out, because active NF-kB complexes are assembled from various combinations of RelA, RelB, c-Rel, p50, p52, NFKB1 (p105) etc., it may be possible to specifically block the generation and/or assembly of a single monomeric species of NF-kB by limiting the abundance of one of the subunits of NF-kB by genome editing, including knock-out technologies and/or the Cas9/CRISPR editing system (Wang et al, 2018 ; Dai et al, 2020 ; Katti et al, 2022 ); (iv) NF-kB is directed to bind to its genomic targets by topological features located in certain promoter DNA sequences; therefore, these highly specific promoter DNA binding sites can be masked, blocked, or modulated using genome blocking technologies involving small non-coding RNA (sncRNA), NF-kB decoy sequence, and/or Cas9/CRISPR editing strategies (Taganov et al, 2006 ; Christian et al, 2016 ; Zhang et al, 2017 ; Baltimore, 2019 ; Dai et al, 2020 ; Katti et al, 2022 ; Yoon et al, 2022 ); (v) specific upregulated miRNA abundance and speciation may be blocked or modulated using chemically stabilized anti-miRNA strategies or by targeting miRNA processing enzymes, thus preventing the creation of a fully active and/or biologically available miRNA species; (vi) directed delivery systems to the brain and/or CNS or other tissue and/or organ systems to minimize unwarranted off-target effects; (vii) long-term systemic ingestion of low-dose NF-κB inhibitors including dietary-administered flavonoids, lignans, diterpenes and sesquiterpenes, saponins, polysaccharides, polyphenols, biological fiber, and other natural products that may have general beneficial effects on reducing pro-inflammatory signaling, carcinogenesis, and neurodegeneration by chronic dampening of NF-κB activities. These have been used for millennia in the pharmacopeia associated with ethnic biomedical-treatment approaches (Gilmore and Herscovitch, 2006 ; Li et al, 2020a , b ; Olajide and Sarker, 2020 ; Uddin et al, 2021 ; Al-Khayri et al, 2022 ...…”

“…(vii) long-term systemic ingestion of low-dose NF-κB inhibitors including dietary-administered flavonoids, lignans, diterpenes and sesquiterpenes, saponins, polysaccharides, polyphenols, biological fiber, and other natural products that may have general beneficial effects on reducing pro-inflammatory signaling, carcinogenesis, and neurodegeneration by chronic dampening of NF-κB activities. These have been used for millennia in the pharmacopeia associated with ethnic biomedical-treatment approaches (Gilmore and Herscovitch, 2006;Li et al, 2020a,b;Olajide and Sarker, 2020;Uddin et al, 2021;Al-Khayri et al, 2022;Das et al, 2022); and/or (viii) any combination of these therapeutic strategies. Regarding the creation and testing of synthetic NF-kB modulatory or blocking compounds, about ∼80 pharmaceutical companies are currently in the pursuit of more effective, directed and specifically targeted NF-kB inhibitors for clinical application in human diseases involving excessive NF-kB activation and signaling (https://www.…”

Taro (Colocasia Esculenta (L.) Schott) Extract didn’t Increase Superoxide Dismutase (SOD) but Decrease C-Reactive Protein (CRP) in Male Wistar Rat (Rattus Norvegicus) Diabetes Mellitus Model

“…Flavonoids, as antioxidants, can protect cells against the effects of reactive oxygen species (ROS). Flavonoids' capacity to act as an anti-diabetic has also been extensively researched (Al-Khayri et al, 2022;Bisala et al, 2019;Noviardi et al, 2020). Various plants have been studied and searched for flavonoid content in order to employ them as a medicine companion or supplement.…”