Anti-Inflammatory, Antioxidant, Moisturizing, and Antimelanogenesis Effects of Quercetin 3-O-β-D-Glucuronide in Human Keratinocytes and Melanoma Cells via Activation of NF-κB and AP-1 Pathways

Abstract

Quercetin 3-O-β-D-glucuronide (Q-3-G), the glucuronide conjugate of quercetin, has been reported as having anti-inflammatory properties in the lipopolysaccharide-stimulated macrophages, as well as anticancer and antioxidant properties. Unlike quercetin, which has been extensively described to possess a wide range of pharmacological activities including skin protective effects, the pharmacological benefits and mechanisms Q-3-G in the skin remained to be elucidated. This study focused on characterizing the skin protective properties, including anti-inflammatory and antioxidant properties, of Q-3-G against UVB-induced or H2O2-induced oxidative stress, the hydration effects, and antimelanogenesis activities using human keratinocytes (HaCaT) and melanoma (B16F10) cells. Q-3-G down-regulated the expression of the pro-inflammatory gene and cytokine such as cyclooxygenase-2 (COX-2) and tumor necrosis factor (TNF)-α in H2O2 or UVB-irradiated HaCaT cells. We also showed that Q-3-G exhibits an antioxidant effect using free radical scavenging assays, flow cytometry, and an increased expression of nuclear factor erythroid 2- related factor 2 (Nrf2). Q-3-G reduced melanin production in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 cells. The hydration effects and mechanisms of Q-3-G were examined by evaluating the moisturizing factor-related genes, such as transglutaminase-1 (TGM-1), filaggrin (FLG), and hyaluronic acid synthase (HAS)-1. In addition, Q-3-G increased the phosphorylation of c-Jun, Jun N-terminal kinase (JNK), Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and TAK1, involved in the MAPKs/AP-1 pathway, and the phosphorylation of IκBα, IκB kinase (IKK)-α, Akt, and Src, involved in the NF-κB pathway. Taken together, we have demonstrated that Q-3-G exerts anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis properties in human keratinocytes and melanoma cells through NF-κB and AP-1 pathways.

PLA Nanofibers for Microenvironmental-Responsive Quercetin Release in Local Periodontal Treatment

“…In periodontally healthy conditions, ROS contribute to the oxidative killing of pathogens, while, during periodontitis, the homeostatic imbalance between ROS and antioxidant defense systems acts as intracellular signal transducers that promote cell death and cause tissue damage. Several studies have demonstrated the capability of QUE to reduce either in vitro and in vivo oxidative stress and inflammation [ 47 , 48 , 49 , 50 , 51 ]. In particular, the antioxidant effects of QUE seem to be related to the presence in a heterocyclic ring of a catechol group (a 2,3-double bond at position 3 and a hydroxyl substitution at position 5) [ 50 , 52 ].…”

An Inflamed and Infected Reconstructed Human Epidermis to Study Atopic Dermatitis and Skin Care Ingredients

“…The significant improvement in the barrier function (trans-epidermal water loss values decreased by 21% and 27% versus baseline at 1 and 2 months, respectively) and EASI score (decreased by 39% and 49%) confirmed the relevance of our model to evaluate ingredients that can be used to improve atopic-prone skin. The activity of the Castanea sativa extract may be explained by its flavonoid profile, particularly flavonoid glucosides, and among them, the major compounds miquelianin (Quercetin-3-O-glucuronide) and astragalin (Kampferol 3-O- glucuronide), as these two compounds are known as NF kB pathway modulators [ 52 , 53 , 54 , 55 ].…”

Hyperoside and Quercitrin in Houttuynia cordata Extract Attenuate UVB-Induced Human Keratinocyte Cell Damage and Oxidative Stress via Modulation of MAPKs and Akt Signaling Pathway

“…Indeed, in an in vitro study, the aglycone form of hesperidin is efficiently taken up by skin fibroblasts, but does not protect them against UVA-induced damage, while hesperetin-7-glucuronide could not be detected in skin fibroblasts as an aglycone, but it is protective against UVA radiation [ 58 ]. In contrast, quercetin and its major metabolites, quercetin-3-glucuronide, exhibited a cytoprotective activity on UVB-induced keratinocyte cell damage [ 59 ]. Therefore, the biotransformation and active metabolites of quercitrin and hyperoside in keratinocytes need to be further investigated.…”