Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes

Abstract

Icariin (ICA) and icaritin (ICT) exhibit many pharmacological functions including anti-osteoporosis, anti-cardiovascular, and anti-cancer activities; however, there are few comprehensive studies that track the detailed effects on UVB-induced photoaging. The recovery effects of ICA and ICT were investigated in UVB-irradiated human keratinocytes (HaCaTs). The results indicated that ICT and ICA showed strong radical scavenging activity, and the reactive oxygen species (ROS) scavenging activity of ICT was superior. UVB-induced matrix metalloproteinase-1 (MMP-1) expression was blocked by ICA via the inhibition of mitogen-activated protein kinase/activator protein 1 (MAPK/AP-1), which directly reduced extracellular matrix (ECM) degradation. ICT activated nuclear factor erythroid 2 related factor 2 (Nrf2) to improve the anti-oxidative stress capacity and suppress nuclear factor-κB (NF-κB) activation, decreasing vascular endothelial growth factor (VEGF) protein, and inflammatory cytokines induced ECM degrading enzyme secretion. Moreover, ICT was more advantageous to improve transforming growth factor beta 1 (TGF-β1) and procollagen type I expression than ICA, promoting the synthesis of collagen. Therefore, ICA and ICT have potential to treat UVB-induced oxidative stress, inflammation and photoaging, and will be posited as a novel strategy to alleviate photodamage.

Protective Effect of Polymethoxyflavones Isolated from Kaempferia parviflora against TNF-α-Induced Human Dermal Fibroblast Damage

“…MAPK, together with two downstream pathways, namely AP-1 and NF-κB, associated with oxidative stress and inflammatory responses, play a central role in regulating skin damage [36][37][38]. ROS and inflammatory cytokines activate MAPKs, inducing an increase in the expression of c-Jun and c-Fos in the nucleus.…”

“…In the epidermis and dermis, AP-1 triggers the expression of MMP-1, MMP-9, and MMP-3, which degrade collagen and other components of the skin ECM [37]. In addition, activation of MAPKs also induces phosphorylation and translocation of NF-κB, which leads to the production of MMP-1 and pro-inflammatory cytokines [36,39]. Thus, reversal of these pathways plays an important role in delaying the aging progress of the skin.…”

Advances in research on the active constituents and physiological effects of Ganoderma lucidum

“…UV is a primary environmental factor implicated in skin aging; it causes coarse wrinkling, dryness, and laxity (Kong et al 2018). UVB irradiation stimulates MMP-1 secretion and reduces the synthesis of collagen and elastin, which can accelerate skin senescence (Hwang et al 2018). The extract of G. lucidum can inhibit UVBinduced MMP-1 expression and increased procollagen expression by inhibiting ERK pathways .…”

<p>Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65</p>

“…Icariin (ICA) is an active polyphenol extracted from the plant Epimedium genus. As previous researches reported, ICA has a variety of pharmacological benefits including anti-osteoporosis, 7 anti-cardiovascular, 8 antitumor 9,10 and organ protection. 11,12 Interestingly, ICA has been proved to suppress ovarian cancer, 9 thyroid cancer, 10 colon cancer 13 and osteosarcoma 14 via different signals.…”