In a recent study published in the journal Biomedicine & Pharmacotherapy, researchers explored the anti-allergic and anti-inflammatory properties of flavonoids.
Chronic inflammation is crucial to the initiation and progression of chronic disorders such as diabetes, cancer, hypertension, asthma, and allergies. Bioactive flavonoids are abundant in numerous food groups, including vegetables, nuts, fruits, beverages, and grains. Recent research on flavonoids has revealed their ability to regulate or prevent inflammation. Due to their antioxidant, anti-inflammatory and immunomodulatory capacities, flavonoids are an indispensable ingredient in pharmaceutical, nutraceutical and medical applications. However, extensive research is required to understand the anti-inflammatory mechanism of these compounds.
Anti-inflammatory and anti-allergic potential of dietary flavonoids: a review. Image credit: Danijela Maksimovic / Shutterstock
Flavonoids as effective anti-inflammatory agents
Flavonoids work as anti-inflammatory agents by blocking transcription factors as well as regulatory enzymes responsible for inflammation and its propagation, among other mechanisms. Several kinases, including protein C kinase, phosphoinositol kinase, tyrosine kinase, cyclin-dependent kinase-4, or phosphatidylinositol kinase, are involved in signal transduction through lipid or protein phosphorylation and play essential roles in cellular activation during inflammation. Flavonoids can potentially affect protein kinases by suppressing nuclear factor kappa-B (Nf-κB). Several studies have shown that flavonoids can modulate IkB and Nf-κB, which directly correlate with cellular activation. In addition, they regulate transcription factors such as signal transducer and activator of transcription (STAT)-6 and GATA-3 of CD4+T helper 2 (Th2) cytokines.
Flavonoids as an anti-allergic agent
Approximately four different types of allergic immunological responses develop after exposure to allergens or medications. Type 1, which is mediated by Th cells, is the focus of research. It consists of two phases, namely the inductive phase which involves the formation of immunoglobulin (Ig)-E against the allergen in the presence of Th2 predominance. The second phase is the triggering phase which involves the robust secretion of chemical mediators from immune cells, including mast cells, which then re-interact with the allergen. The interference of flavonoids with the activation of Th cells appears to be the main mechanism for suppressing allergic reactions. With this approach, flavonoids may play a pathological role in the treatment of allergy-related conditions.
In vitro and in vivo studies of flavonoids
Luteolin, myricetin, kaempferol, and quercetin were found to be beneficial against allergy-specific cytokines in in vitro and in vivo experiments. All have been reported to inhibit the generation of interleukin (IL)-4 and IL-13 from mast cells and basophils.
Quercetin
Quercetin is a potential component due to its antioxidant action in the elimination of radicals and the anti-allergic characteristics that are manifested through immunological activation. It also functions as an antihistamine and anti-inflammatory agent by decreasing the production of histamine by both basophils and mast cells, respectively, and preventing the secretion of proinflammatory cytokines. In vitro and in vivo studies showed the anti-allergic and anti-inflammatory properties of quercetin. Both galangin and quercetin alleviated atopic dermatitis in lipopolysaccharide (LPS)-activated macrophages by targeting NF-κB, extracellular signal-regulated kinases (ERKs)-1/2 and c-Jun N-terminal pathways kinase (JNK). Furthermore, galangin and quercetin alone or together reduce serum IgE and improve skin lesions in a balb-c mouse model of atopic dermatitis (AD).
Kaempferol
Kaemferol is a flavonol of plant origin with anti-allergic, anti-inflammatory and antioxidant activities demonstrated in animal and human studies. By interfering with NF-κB signaling, it significantly controls allergic airway inflammation in mice. Kaempferol decreased the expression of CD69 and the generation of allergen-inducing inflammatory cytokines, such as IL-12. In addition, pulldown experiments showed that kaempferol reduces the activity of multidrug resistance-associated protein 1 (MRP-1) by directly binding to it. Kaempferol inhibited the TAK1-IKK-mediated NF-κB pathway as well as JNK phosphorylation in activated T cells. Similar to in vitro research, kaempferol improved the onset of atopic dermatitis among mice.
Myricetin
Myricetin has antioxidant, anti-inflammatory and anti-allergic properties. Toluene 2,4-diisocyanate (TDI)-induced allergic mice showed a decrease in sneezing, erythema, rhinorrhea and edema after oral treatment of Sonneratia caseolaris crude extract. Polyphenolic chemicals, particularly vanillic acid, myricetin, and ellagic acid, have also been found to reduce allergic symptoms by binding directly to histamine receptors and suppressing cell cytokine production. Th cells involved in allergic disease.
Luteolin
The antiallergic activity of luteolin was investigated in Balb-c mice with egg-albumin-induced asthma. In a mouse model, animals treated with luteolin showed reduced allergy symptoms, including decreased Th2-mediated inflammatory cell infiltration and inflammatory cytokines. Rats with allergic rhinitis were studied to determine how luteolin helps alleviate allergic inflammation and Th1/Th2 balance by regulating the toll-like receptor 4 (TLR4)/NF-κB pathway. In ovum-induced allergic mice, Artemisia argiyi component luteolin significantly decreased airway hypersensitivity, inflammatory cell counts, Th2 cytokines, and IgE.
Overall, the results of the study showed that flavonoids possess anti-inflammatory, antioxidant and anti-allergic properties. Recent studies of four key anti-inflammatory and anti-allergic flavonoids have confirmed their beneficial effects on allergic diseases by balancing Th1/Th2 cells and impairing basophil and mast cell stimulation.
Journal reference:
- Allah Rakha, Nehal Umar, Roshina Rabail, Masood Sadiq Butt, Marek Kieliszek, Abdo Hassoun, Rana Muhammad Aadil, Anti-inflammatory and anti-allergic potential of dietary flavonoids: a review, Biomedicine and Pharmacotherapy, Volume 156, 2022, 113945, ISSN45 0753- 3322, DOI: