Luteolin suppresses UVB‐induced photoageing by targeting JNK1 and p90^RSK2

Abstract

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.

Luteolin Suppresses Ultraviolet A- and B-induced Matrix Metalloproteinase 1- and 9 Expression in Human Dermal Fibroblast Cells

“…Similar to our results, luteolin at 1-5 µM significantly inhibited UVA (15 J/cm 2 )-induced MMP-1 mRNA expression in human keratinocyte HaCaT cells [29]. In another study, luteolin at 5-10 µM inhibited UVB (10 mJ/cm 2 )-induced MMP-1 expression in a dose-dependent manner in human keratinocyte HaCaT cells [30]. Human dermal fibroblast cells exposed to UVA (6.3 J/cm 2 ) induced MMP-1 when luteolin was inoculated into the cell culture at 1-10 µM, reducing the expression of MMP-1 protein and mRNA [31].…”

“…However, a few studies have investigated the direct modulatory effects of luteolin on MMPs during photoaging [29][30][31][32][33]. Moreover, to date, a relationship between luteolin and MMP-9 against both UVA and UVB-irradiation has not been demonstrated, despite the importance of MMP-9 and collagen breakdown during photoaging using HDF cells [19].…”

Novel extraction techniques and pharmaceutical activities of luteolin and its derivatives

“…The longer extraction time and the high temperature will enhance the chances of thermal degradation (Zhang, Lin, & Ye, ). The extraction conditions of 50°C for 2 hr using solvent sample ratio of 10:1 (ml/g) for are typically used for continuous hot solvent extraction and considered most appropriate for optimal extract and isolation of target molecule (Lim et al, ). Regarding yield recovery through SE technique, dichloromethane and ethanol are reported as best solvents.…”

Phytochemicals for the Prevention of Photocarcinogenesis

“…Studies using HaCaT cells found that luteolin inhibits UVA‐induced AP‐1 activation as well as c‐Fos, c‐Jun and MMP‐1 expressions . Luteolin also inhibited UVB‐induced MMP expression by suppressing JNK1 and p90RSK2 activity in HaCaT cells . Similar effects were observed when UVA‐exposed dermal fibroblasts were treated with luteolin.…”