Synthesis and skin gene analysis of 4'-acetoxy-resveratrol (4AR), therapeutic potential for dermal applications.
Resveratrol (RV) 1, a plant polyphenol, has proven effective in commercial products yet drawbacks include low bioavailability due to rapid metabolism. Structural modifications have led to a 4'-acetoxy analog 2 (4AR) now produced using a selective one-step esterification reaction. The one-step synthesis is shown together with expression of skin genes using human dermal models to establish 4AR 2 benefits to skin health. 4AR 2 at 1% in qPCR experiments using a human skin model significantly increased gene expression of the anti-aging factor, SIRT 1 by over 3.3-fold, extracellular matrix proteins collagen III, IV, elastin and tissue inhibitors of metalloproteinases (TIMP 1, 2), anti-oxidants CAT, LOX, superoxide dismutase (SOD 1, 2), metallothioneins (MT1H, MT1H), skin aging biomarkers fibrillin (FBN1), laminin (LAMB1), proliferating cell nuclear antigen (PCNA), skin growth factors (HBEGF, IGF1, NGF and TGF). 4AR 2 also decreased gene expression of inflammatory and skin-aging molecules (IL-1, IL-6, IL-8, COX-2, TNGRSF) and S100 calcium binding proteins A8, A9. These findings suggest that 4AR 2 has potential for topically treatment and prevention of skin aging.
Department of Physiology and Developmental Biology/The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA.
Edwin D
ED
Lephart
Department of Chemistry, Brigham Young University, Provo, UT 84602, USA.
Mark J
MJ
Acerson
Department of Chemistry, Brigham Young University, Provo, UT 84602, USA. Electronic address: mbandrus@chem.byu.edu.
Merritt B
MB
Andrus
D015415:Biomarkers / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D006801:Humans; D015394:Molecular Structure; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C000621328:4'-acetoxy-resveratrol; D015415:Biomarkers; D013267:Stilbenes
Esterification; Extra cellular matrix; Gene expression; Human skin; Polyphenol; Resveratrol