Study On Mechanism Of A Glyceroglycolipid From Brown Algae Ishige Okamurae Inhibiting Photoaging In UVB-induced HaCaT Cells

Purpose:Ultraviolet radiation in sunlight is the culprit of premature skin aging.Retinoic acid and its derivatives have significant effects in the treatment of skin photoaging.However,frequently use of it can lead to serious by-effects such as dry skin,redness and inflammation.In contrast,marine-derived natural medicine substitutes have skin affinity and are biodegradable.Studies have found that ultraviolet-induced oxidative stress and inflammatory response are important mechanisms of skin photoaging.The brown algae Ishige okamurae contains many antioxidants and anti-inflammatory agents,which may have huge anti-photoaging potential.Methods:In this study,human immortalized keratinocytes（HaCaT）induced by UVB（Ultraviolet B）are used as a photoaging model to study the anti-photoaging effect and its mechanism of a novel glyceroglycolipid（Ishigoside,IGS）from Ishige okamurae.Results:（1）IGS effectively improves the viability in UVB-damage HaCaT cells.（2）IGS significantly reduces UVB-induced reactive oxygen species（ROS） content in cells and increases antioxidant enzyme expression such as superoxide dismutase（SOD）,heme oxygenase 1（HO-1）and glutathione peroxidase（GPx）as well as stimulated the nuclear factor E2-related factor 2（Nrf2）pathway.This reveals that IGS may up-regulate the expression of antioxidant enzymes by stimulating the Nrf2 pathway,thereby alleviating oxidative stress and protecting DNA from damage.（3）IGS increase the level of procollagen I by inhibiting Smad7 expression and increasing transforming growth factorβ（Transforming growth factor-β1,TGF-β1）and Smad2/3 expression.（4）IGS can effectively inhibit the secretion of MMP-1,MMP-3 and MMP-9.Through molecular docking analysis,the inhibitory effect of IGS may be due to its close-knit combination with MMP-1,MMP-3 and MMP-9 by hydrogen bond and hydrophobic force.（5）IGS can reduce the excessive Ca²⁺level in UVB-induced HaCaT cells.（6）UVB activated the phosphorylation of mitogen-activated protein kinases（MAPK）,high-concentration IGS treatment inhibited phosphorylation of extracellular regulated protein kinases（ERK）,and p38.However,it has no obvious regulatory effect on the phosphorylated expression of c-Jun N-terminal kinase（JNK）.（7）IGS obviously reduces the DNA binding activity of activator protein-1（AP-1）by inhibiting the phosphorylation expression of c-Fos and c-Jun and the nuclear transport.It suppresses the expression of matrix metalloproteinases.（8）IGS treatment inhibits the expression of NO and inflammatory factors induced by UVB,which may be because it inhibits the phosphorylation and degradation of Inhibitor of NF-κB（IκB）,thereby inhibiting and transcription factor-B（Nuclear factor-kappa B,NF-κB）p65 phosphorylation expression,nuclear transfer and NF-κB DNA binding activity.It demonstrated that IGS possess good anti-inflammatory activity.Conclusion:The results of this study show that IGS has good anti-photoaging activity.Its activities may be derived from its antioxidant capacity and good anti-inflammatory effect,which has huge potential for development and utilization.