Effect of Quercetin in the UV-Irradiated Human Keratinocyte HaCaT Cells and A Model of Its Binding To p38 MAPK

Abstract

Quercetin is a major dietary flavonoid found in onions, apples, tea, and red wine, and potentially has beneficial effects on disease prevention. We carried out this study to investigate the effect of quercetin on UVB-induced matrix metalloproteinase-1 (MMP-1) expression in human keratinocyte HaCaT cells and to further understand the mechanisms of its action. The anti-inflammatory activity of quercetin was investigated and quercetin significantly suppressed the NO production in LPS-stimulated RAW264.7 mouse macrophages. Post treatment of quercetin decreased UV irradiation-induced phosphorylation of JNK, p38 MAPK, and ERK by 91%, 21%, and 17%, respectively. MMP-1 is mainly responsible for the degradation of dermal collagen during the aging process of human skin and quercetin suppressed the UVB-induced MMP-1 by 94%. Binding studies revealed that quercetin binds to p38 with high binding affinity (1.85 × 10 6 M −1). The binding model showed that the 4′-hydroxy groups of the B-ring of quercetin participated in hydrogen bonding interactions with the side chains of Lys53, Glu71, and Asp168 and the 5-hydroxy group of the A-ring formed a hydrogen bond with the backbone amide of Met109. The major finding of this study shows that quercetin inhibits phosphorylation of JNK, p38 MAPK, and ERK pathway leading to the prevention of MMP-1 expression in human keratinocyte HaCaT cells. Therefore, our findings suggested the potentials of quercetin as a skin anti-photoaging agent.

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation‐induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF‐β/Smad and Inhibition of the MAPK/AP‐1 Pathway in Normal Human Dermal Fibroblasts

“…In this study, the main components, quercetin, naringenin and taxifolin, were detected in ethanolic extract of PS. In agreement with Jnawali et al (22), our data also showed that quercetin prevented UVB-induced MMP-1 expression via inhibition of phosphorylation of MAPK pathway. On the other hand, naringenin was discovered to inhibit UVB irradiation-induced oxidative stress by upregulation of Nrf2 and HO-1 mRNA levels in hairless mice (29).…”

“…The cells were exposed to UVB radiation at 144 mJ cm −2 radiation using a UVB irradiation machine (Bio‐Link BLX‐312; Vilber Lourmat GmbH, France) and then were treated with different concentrations of samples. Quercetin was found to be one of the main components of the EPS, and it was introduced as a positive control in this study for that its photoprotective effects against UVB‐induced aging have been studied previously .…”

Extraction Optimization of Flavonoids from Hypericum formosanum and Matrix Metalloproteinase-1 Inhibitory Activity

“…As shown in Figure 4 , quercitrin suppressed AGE-induced MMP-1 expression by 30 ± 1.7% and 67 ± 2.0% compared to the control level at the concentrations of 250 μg/mL and 500 μg/mL, respectively. Some studies have found that flavonoid compounds from herbs provided significant inhibitory effects on UVB-induced matrix MMP-1 expression in HaCaT cells [ 39 ]. Similarly, we found quercitrin shows significant activity, indicating that quercitrin plays an important role in MMP-1 inhibitory activity.…”

Effect of single clove garlic on clinical symptoms of photoaging in wistar rats exposed with UV-B

“…5 In addition quercetin content is also found in garlic. 6 Based on the previous researches, this antioxidant was found to be able to reduce skin thickness and wrinkles. This antioxidant content may also maintain the elastin and collagen fibers from the effects of UV light exposure as well as increase the production of type I procollagen.…”