Limonene protects human skin keratinocytes against UVB‐induced photodamage and photoaging by activating the Nrf2‐dependent antioxidant defense system

Abstract

Long term exposure to solar ultraviolet B (UVB) radiation is one of the primary factors of premature skin aging and is referred to as photoaging. Also, mammalian skin exposed to UVB triggers an increase in production of α-melanocyte-stimulating hormone (α-MSH), which is critically involved in the pathogenesis of hyperpigmentary skin diseases. This study investigated the protective effect of limonene on UVBinduced photodamage and photoaging in immortalized human skin keratinocytes (HaCaT) in vitro. Initially, we determined cell viability and levels of reactive oxygen species (ROS) in UVB-irradiated HaCaT cells. Pretreatment with limonene increased cell viability followed by inhibition of intracellular ROS generation in UVB-irradiated HaCaT cells. Interestingly, the antioxidative activity of limonene was directly correlated with an increase in expression of endogenous antioxidants, including heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1), and γ-glutamylcysteine synthetase (γ-GCLC), which was associated with enhanced nuclear translocation and activation of NF-E2-related factor-2 (Nrf2). Indeed, Nrf2 knockdown reduced limonene's protective effects. Additionally, we observed that limonene treatment inhibited UVB-induced α-MSH secretion followed by inhibition of proopiomelanocortin (POMC) via suppression of p53 transcriptional activation.Moreover, limonene prevented UVB-mediated depletion of tight junction regulatory proteins, including occludin and zonula occludens-1. On the other hand, limonene treatment significantly decreased matrix metalloproteinase-2 levels in UVB-irradiated HaCaT cells. Based on these results, limonene may have a dermato-protective effect in skin cells by activating the Nrf2-dependent cellular antioxidant defense system.

Effect of Ferulago lutea (Poir.) Grande Essential Oil on Molecular Hallmarks of Skin Aging

“…Regarding isolated compounds, few studies have been conducted using limonene or α-pinene. Limonene was shown to protect keratinocytes against UVB-induced photodamage and photoaging [40]. In addition, this compound is part of the commercial product Garnier Dark Spot Corrector [41], thus reinforcing its skin lightening properties.…”

“…The reported activity might be attributed to the presence of limonene and α-pinene. Indeed, limonene protects HaCaT cells from H 2 O 2 -induced aging [46] and protects human keratinocytes from UVB-induced photoaging by activating Nrf2-dependent antioxidants [40]. UVA-induced photoaging was also prevented by αpinene through the inhibition of matrix metalloproteinase expression [47].…”

Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway

“…A previous study also showed that limonene protects skin keratinocytes from the damaging effect of UVB radiation. This protection occurs by activating the Nrf2-dependent antioxidant defense system, which helps the skin cells to defend themselves against oxidative stress and damage caused by UVB exposure [ 52 ].…”

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin

“…The majority of UVB is absorbed by the ozone layer but still reaches ground level and is absorbed in sufficient amounts to have a deleterious impact on the skin ( 2 , 3 ). UVA and UVB are reported to induce DNA damage, photoaging, and skin cancer ( 4 , 5 ). However, UVA radiation is much less photochemically active and not strongly absorbed by proteins and nucleic acids, so it is generally less harmful than UVB radiation ( 2 , 3 ).…”