Inhibitory effect of naringenin on LPS-induced skin senescence by SIRT1 regulation in HDFs

Abstract

Background: This study aims to investigate the ability of naringenin to regulate the expression of nuclear factor-кB, the upper gene of lipopolysaccharide-induced SIRT1; regulate signal transduction in the extracellular matrix, which plays an important role in the dermis; and alter the matrix metalloproteinase 1 and matrix metalloproteinase 3 gene expression, therefore having suppressing effect on skin cell senescence and deoxyribonucleic acid protection and cell protection effects and confirm naringenin's potential as an important cosmetic ingredient. Methods: The efficacy of naringenin was assessed through reactive oxygen species assay, water-soluble tetrazolium salt assay, nuclear factor-кB luciferase assay, enzyme-linked immunosorbent assay, nicotinamide adenine dinucleotide phosphate oxidase activity assay, and quantitative real-time polymerase chain reaction. Results: Sirt1, which regulates naringenin upstream of the nuclear factor-кB pathway, inhibits nuclear factor-кB activity and decreases matrix metalloproteinase expression level and SIRT1 gene dose-dependently. The results confirmed naringenin had an anti-aging effect on lipopolysaccharide-induced skin senescence. Various age-related biomarkers were used to analyze the inhibitory effect naringenin had on cell senescence progress and oxidative activity. Further experiments also showed naringenin also acted on NADPH oxidase, which produces superoxide (O2-), resulting in inhibiting NADPH oxidase activity. Experimental results reported that naringenin regulated the activity of SIRT1, which is the cause of modern skin cell aging, and in turn had a regenerative effect on reactive oxygen species-induced skin cellular senescence which affects skin elasticity and wrinkles.Conclusions: This study confirmed that naringenin inhibits cellular senescence and regenerates human dermal fibroblasts damaged by lipopolysaccharide, and suggests that naringenin will be a cosmetic ingredient that has cell regenerative effects and anti-aging effects.

Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection

“…These findings suggest its importance in treating cardiometabolic disorders caused by a redox imbalance in the cell. Naringenin promotes the synthesis of the ECM of cartilage and, in turn, improves ageing in both lipopolysaccharide- and reactive oxygen species (ROS)-induced skin senescence through SIRT1-mediated inhibition of NF-κΒ, NADPH oxidase, and matrix metalloproteinases (MMPs) expression in human dermal fibroblast, suggesting regenerative and anti-ageing effects on the dermal cell structure [ 58 ]. However, Lim et al [ 5 ] reported that naringenin did not suppress SASP production in bleomycin-induced senescence.…”

Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis

“…Naringenin has immense biological effects ranging from antimicrobial, anti-inflammatory, antioxidant, anticancer, antidiabetic, cardioprotective, and neuroprotective effects [ 199 ]. In relation to treating allergic immune-related diseases and skin disorders, naringenin has the potential to exhibit antiasthma, anti-aging, and anti-photoaging effects and acts as a skin-protective agent in cosmeceuticals [ 200 , 201 , 202 ]. Previous reports indicated that naringenin ameliorated LPS-induced skin senescence, UV-irradiated skin inflammation, heat-induced skin damage, and skin fibrosis in various experimental models [ 202 , 203 , 204 , 205 ].…”

“…In relation to treating allergic immune-related diseases and skin disorders, naringenin has the potential to exhibit antiasthma, anti-aging, and anti-photoaging effects and acts as a skin-protective agent in cosmeceuticals [ 200 , 201 , 202 ]. Previous reports indicated that naringenin ameliorated LPS-induced skin senescence, UV-irradiated skin inflammation, heat-induced skin damage, and skin fibrosis in various experimental models [ 202 , 203 , 204 , 205 ]. In vascular endothelial cells stimulated by cytokines, naringenin effectively induced SOCS3 expression and promotor activity by suppressing IL-6 stimulated STAT-3 phosphorylation [ 206 ].…”

Flavonoids in Skin Senescence Prevention and Treatment

“…Topical naringenin protects hairless mice from UVBinduced skin damage by inhibiting the production of SASP components (TNF-α, IL-1β, IL-6, and IL-10) and lipid hydroperoxides, while maintaining the expression of antioxidant genes, including glutathione peroxidase 1, glutathione reductase, and the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor [117]. These effects are partly due to the ability of naringenin to decrease NF-кB, MMP-1, and MMP-3 levels [118].…”

“…The mechanisms of the senostatic and senolytic actions of the different flavonoid subtypes in the context of skin aging are summarized in Table 1. ↓ SASP ↓collagen degradation [118] AP-1-activator protein 1 transcription factor; COX-cyclooxygenase; CXCL-chemokine (C-X-C motif) ligand 1; DMSO-dimethyl sulfoxide; Gadd45-growth arrest and DNA damage; GM-CSF-granulocyte-macrophage colony-stimulating factor; IFN-interferon; ILinterleukin; iNOS-inducible nitric oxide synthase; IP10-interferon-γ-inducible protein 10; JAK2-Janus kinase 2; LPS-lipopolysacharide; MAPK-mitogen-activated protein kinase; MCP-methyl chemotaxis protein; MMP-matrix metalloproteinase; NF-κB-nuclear factor κ-light-chain enhancer of activated B cells; Nrf2-nuclear factor erythroid 2-related factor 2; ROS-reactive oxygen species; SASPsenescence-associated secretory phenotype; Smad-SMAD protein; STAT3-signal transducer and activator of transcription; TGF-βtumor growth factor β; TIMP-tissue inhibitor of metalloproteinase proteins; TNF-α-tumor necrosis factor α; TSP-1-thrombospondin 1; UV-ultraviolet; ↓-decrease; ↑-increase.…”