Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual’s quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

“…In recent decades, EA is attracting great attention due to its pronounced antioxidant [15][16][17][18][19][20][21][22][23], anti-inflammatory [24][25][26][27][28][29], antimutagenic [30][31][32][33], and antiproliferative properties [34][35][36][37][38][39] and its therapeutic potential in the treatment of several human diseases. Numerous studies have shown that EA may be involved in regulating a spectrum of cellular signaling pathways to prevent, mitigate, or slow down the progression of chronic disorders, including cardiovascular [40][41][42][43] and neurodegenerative diseases [44][45][46][47], diabetes [48][49][50][51], and cancer [38,[52][53][54].…”

Post-Inflammatory Hyperpigmentation in Dark Skin: Molecular Mechanism and Skincare Implications

“…The compound can moreover modulate the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK1/2-ERK) and the Janus kinase signal transducer/activator of transcription (JAK/STAT) pathways in response to the treatment of the cells with pro-inflammatory factors TNF-α and interferon γ (IFN-γ). 73 Cellular targets of luteolin involve the major pathways regulating inflammation - Nf-κB, activator protein 1 (AP-1) and signal transducer and activator of transcription (STAT-3). 74 N-acetyl glucosamine (NAG) normalizes the stratum corneum by up-regulation of the differentiation markers keratin 10 and involucrin.…”

Selected Seeds as Sources of Bioactive Compounds with Diverse Biological Activities

“…Several studies have demonstrated anti-inflammatory properties of ellagic acid, a dimeric derivative of gallic acid abundant in blackberry seeds, and present in many different plant species [ 3 , 85 , 86 , 87 ].…”

“…In HaCaT (human, adult, low calcium, and high temperature) keratinocytes stimulated by tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ), 250–1000 μM ellagic acid suppressed the expression of pro-inflammatory interleukin 6, and decreased relative mRNA expression of chemokines—thymic stromal lymphopoietin (TSLP), macrophage-derived chemokine (MDC), and thymus and activation-regulated chemokine (TARC). Furthermore, it inhibited pro-inflammatory Janus kinase/signal transducer and activator of transcription (JAK/STAT) and phosphoinositide 3-kinase/AKTsignaling pathways [ 86 ].…”