Luteolin Prevents UVB-Induced Skin Photoaging Damage by Modulating SIRT3/ROS/MAPK Signaling: An in vitro and in vivo Studies

Abstract

The aim of this study was to investigate the role of luteolin in the mechanism of ultraviolet radiation B (UVB)-induced photoaging. An in vivo photoaging model was established using UVB irradiation of bare skin on the back of rats, and an in vitro photoaging model was established using UVB irradiation of human dermal fibroblasts (HDF). Skin damage was observed using hematoxylin-eosin (HE) and Masson staining, skin and cellular reactive oxygen species (ROS) levels were detected by DHE and DCF fluorescent probes, mitochondrial membrane potential was detected by JC-1 staining, and protein expressions were detected by immunofluorescence and Western Blot. Results from animal experiments showed that luteolin reduced UVB-induced erythema and wrinkle formation. Results from cellular assays showed that luteolin inhibited UVB-induced decrease in cell viability. In addition, in vitro and in vivo experiments showed that luteolin reduced oxidative stress levels, decreased activation of matrix metalloproteinases (MMPs) and increased collagen expression. Continued cellular experiments using 3-TYP, an inhibitor of Sirtuin 3 (SIRT3), revealed a loss of cellular protection by luteolin and a decrease in collagen, suggesting that luteolin acts by targeting and promoting SIRT3. luteolin is involved in the protection of skin cells against UVB radiation-induced ageing via the SIRT3/ROS/mitogen-activated protein kinases (MAPK) axis and it may be a promising therapeutic agent for the prevention of UVB photoaging.

Anti-photoaging effects of flexible nanoliposomes encapsulated Moringa oleifera Lam. isothiocyanate in UVB-induced cell damage in HaCaT cells

“…Proteolytic enzymes such as MMPs and elastases are produced by epidermal keratinocytes and fibroblasts in the mediation of ECM remodeling (Philips et al., 2011 ). The MMPs initiate the photoaging of the skin by acting as collagenases (Mu et al., 2021 ). Collagen and elastin are the major structural proteins in the ECM.…”

Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside

“…In sum, flavonoids are molecules with a series of beneficial effects, exerting anti-inflammatory [ 6 , 9 ], antioxidant [ 9 ], pro-apoptotic [ 19 ], anti-aging [ 1 , 20 ], neuroprotective [ 21 ], anti-cancer [ 22 ], antimicrobial [ 23 , 24 , 25 ], antiviral [ 26 , 27 , 28 ], anti-parasitic [ 28 , 29 ], anti-angiogenic [ 9 ], cardioprotective [ 30 ], and antidiabetic [ 31 ] properties.…”

“…Recent studies have reported the anti-aging property of luteolin on rat skin models [ 20 ]. The skin aging is mainly due to solar ultraviolet radiation exposure, which induces inflammation; the formation of pyrimidine dimers (DNA damage); and oxidative stress that affects lipids, proteins, mitochondria, and DNA.…”

“…On the other hand, luteolin could stabilize mitochondrial function, restoring SIRT-3 expression, downregulated by oxidative stress [ 20 ]. In fact, SIRT-3 (NAD + -dependent lysine deacetylase) avoids ROS accumulation in the mitochondria by deacetylating mitochondrial enzymes that show increased ROS scavenging activity.…”

Preparation and Evaluation of Liposomes and Niosomes Containing Total Ginsenosides for Anti-Photoaging Therapy

“…UV radiation is a major factor in the acceleration of both forms of skin aging by causing excessive reactive oxygen species (ROS) production ( Chung 2003 ; Ho et al, 2005 ; Wolf et al, 2020 ). ROS can upregulate heterodimer-activated protein 1 (AP-1), which is composed of c-Fos and c-Jun proteins, by activating mitogen-activated protein kinase (MAPK), which induces the synthesis of matrix-degrading enzymes such as matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase 3 (MMP-3) ( Lee et al, 2020 ; Mu et al, 2021 ; Wan et al, 2021 ). MMPs degrade collagen and elastin in the extracellular matrix in vivo .…”