Quercetin – Part II: Anti-Inflammatory Action

In the previous article we saw how quercetin, a flavonoid found in various types of fruits and vegetables, shows a marked anti-allergic activity by acting on the immune system, and is particularly effective for treating allergic rhinitis when administered by inhalation - topical route.

In addition to its anti-allergic activity, quercetin also has anti-inflammatory activity, as demonstrated by several studies, and therefore could be useful for treating inflammation of the nasal mucosa associated with allergic diseases. Several clinical studies have shown that quercetin exhibits, both in vitro and in vivo, anti-inflammatory activity.

The potent anti-inflammatory effects exerted by quercetin are exerted mainly through the inhibition of cytokine production, the reduction of cyclooxygenase and lipoxygenase expression, and the maintenance of the stability of mast cells, immune cells important in the pathogenesis of allergic responses and autoimmune diseases.

They influence the release of many cytokines involved in inflammatory reactions such as interleukin 8 (IL-8) and tumor necrosis factor (TNF). Quercetin inhibits the release of histamine and other allergic and inflammatory substances at the level of mast cells by:

• Stabilization of mast cell membranes.
• Inhibition of mast cell activation through inhibition of Ca ²⁺ influx, release of histamine, leukotrienes and prostaglandins and protein kinase activation.
• Inhibition of IgE-mediated allergic mediator release from mast cells.

For this reason, quercetin is suitable for the treatment of allergic inflammatory diseases of mast cell origin such as asthma, as we saw in the previous article. In addition to its action on mast cells, quercetin exerts its anti-inflammatory effect through:

• Inhibition of the activation of some protein kinases such as p38 mitogen-activated protein kinase, extracellular signal-related kinases (ERK1/2) and nuclear factor kappa B (NF-κB).
• Reduction of the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin 6 (IL-6).
• Increased secretion of anti-inflammatory cytokines such as interleukin 10 (IL-10).

Furthermore, quercetin, thanks to its chemical structure, is a powerful antioxidant, an activity that it exerts mainly in mice by suppressing free radicals and upregulating the levels of antioxidant enzymes including glutathione peroxidase, superoxide dismutase and catalase.

The antioxidant activity of quercetin counteracts cellular damage linked to reactive oxygen species and therefore prevents inflammatory phenomena linked to excessive oxidative stress.

The anti-inflammatory action of quercetin occurs both systemically and topically, as shown by several studies conducted on rheumatoid arthritis.

In particular, it has been seen how the administration of quercetin-based gel to animal models of rheumatoid arthritis (in vivo studies) has shown greater skin permeability, thus increasing the therapeutic efficacy and the anti-inflammatory effect.

References

• Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and Its Anti-Allergic Immune Response. 2016 May 12;21(5):623.
• Song JY, Truong DV, Yang BS. Quercetin Shows the Pharmacological Activity to Simultaneously Downregulate the Inflammatory and Fibrotic Responses to Tissue Injury in Association with its Ability to Target Multi-Kinases. Pharmacology. 2018;102(3-4):142-153.
• Jafarinia M, Sadat Hosseini M, Kasiri N, Fazel N, Fathi F, Ganjalikhani Hakemi M, Eskandari N. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol. 2020 May 14;16:36.
• Li Y, Yao J, Han C, et al. Quercetin, Inflammation and Immunity. Nutrients. 2016;8(3):167. Published 2016 Mar 15.
• Shen P, Lin W, Deng X, et al. Potential Implications of Quercetin in Autoimmune Diseases. Front Immunol. 2021;12:689044. Published 2021 Jun 23.
• Gokhale JP, Mahajan HS, Surana SJ. Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro studies. Biomed Pharmacother. 2019 Apr;112:108622.