Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes

Abstract

Background: Atopic dermatitis (AD) is a common inflammatory skin disease with complex pathogenesis. Natural flavonoids exhibit strong anti-inflammatory and antioxidant properties in many human diseases. In this study, the potential bioactive effect of quercetin, a polyphenolic plant-derived flavonoid, on the AD model of human keratinocytes was evaluated. Methods: Immortalized human HaCaT keratinocytes were treated with interleukin (IL) -4, -13, and tumor necrosis factor-a to mimic AD features in vitro. Then effects of quercetin on inflammation, oxidative stress, and wound healing were assessed. Results: Pretreatment of the cells with 1.5 mM of quercetin significantly reduced the expression of AD-induced IL-1b, IL-6, IL-8, and thymic stromal lymphopoietin, while it strongly enhanced the expression of superoxide dismutase-1 (SOD1), SOD2, catalase, glutathione peroxidase, and IL-10. Quercetin promoted wound healing by inducing epithelial-mesenchymal transition, which was supported by the upregulation of Twist and Snail mRNA expression. Unexpectedly, quercetin pretreatment of AD-induced cells upregulated the mRNA expression of occludin and E-cadherin, while downregulating matrix metalloproteinase 1 (MMP1), MMP2, and MMP9 expression. The pretreatment inhibited AD-induced phosphorylation of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase (ERK1/2 MAPK) and the expression of nuclear factor-kappa B (NF-kB), but it did not alter signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion:Quercetin may serve as a potential bioactive substance for atopic dermatitis-related symptoms through anti-inflammatory and antioxidant activities along with its acceleration of wound healing via ERK1/2 MAPK and NF-kB pathways.

Comprehensive Phytochemical Profiling of Polyherbal Divya-Kayakalp-Vati and Divya-Kayakalp-Oil and Their Combined Efficacy in Mouse Model of Atopic Dermatitis-Like Inflammation Through Regulation of Cytokines

“… 73 Additionally, Quercetin pre-treatment reduced oxidative stress through the generation of antioxidants within the in vitro model for AD using HaCaT cells treated with IL-4, IL-13, and TNF-α. 74 Quercetin also increased the mRNA expression of occludin and E-cadherin, while downregulating MMP1, MMP2, and MMP9 expression stimulating wound healing in stimulated HaCaT cells as well as, downregulated phosphorylation of MAPK, and NF-κB reducing inflammation. 74 …”

Biosynthesis of Organic Nanocomposite Using Pistacia vera L. Hull: An Efficient Antimicrobial Agent

“…is causes the substance to block the chemical pathway of some of the ways in which inflammation is produced. As a result, quercetin is able to reduce pain from arthritis, gout, rheumatism, and general inflammation, in which people usually suffer from [60]. þIt has been shown to have different aldose reductase inhibitory properties.…”

Potential of Tamanu (Calophyllum inophyllum) Oil for Atopic Dermatitis Treatment

“…Several studies showed that wound healing was impaired in AD, as shown by Beken et al, in 2020, where HaCaT induced with AD-stimulating agents showed delayed wound healing [54].…”

“…e expression of these genes is necessarily slightly increased in wound healing to facilitate cell migration. However, overexpression of these genes could actually interfere with tissue repair since it will result in excessive ECM degradation in the tissue regeneration stage [54]. Another study by Zhao et al also showed delayed wound healing in IL-4 Tg mice model for AD despite the robust keratinocyte proliferation specific to AD pathophysiology [55].…”