title: Protective effects of equol and their polyphenolic isomers against dermal aging: microarray/protein evidence with clinical implications and unique delivery into human skin.
abstract: BACKGROUND
  Equol is a polyphenolic/isoflavonoid molecule that can be expressed as isomers. However, the characteristics of the equol isomers on dermal gene/protein expression and human skin percutaneous absorption remain unknown.
  
  
  OBJECTIVE
  Perform a comprehensive investigation on equol as: R-equol, racemic equol or S-equol to determine their differential expression of skin-related genes, quantify collagen expression and determine percutaneous absorption in human skin.
  
  
  METHODS
  Quantified: (i) gene expression/mRNA levels via gene array technology using human skin equivalents with equol exposure at 1.2% in qPCR experiments, (ii) in vitro collagen expression in human fibroblasts, and (iii) percutaneous absorption by Franz cell techniques.
  
  
  RESULTS
  In the qPCR studies, only three genes displayed the greatest significant expression by S-equol, whereas 16 genes displayed the greatest significant levels (either stimulation or inhibition) by R-equol and/or racemic equol, such as extracellular matrix proteins (i.e., collagen and elastin), nerve growth factor, aging genes [FOS, 100 A8 and A9 calcium-binding proteins, 5α-reductase type 1, and matrix metalloproteinases (1, 3, and 9)], and inflammatory genes (e.g., interleukin-1 alpha, interleukin-6, and cyclooxygenase-1). Collagen type I expression in fibroblasts was greater with racemic versus S-equol treatment at 1 and 10 nM. Percutaneous absorption demonstrated high sequestering in keratinocytes with subsequent accumulation/release over time.
  
  
  CONCLUSIONS
  Overall, these results illustrate the significant differences in mirror-image molecules or isomers of equol where R-equol and/or racemic equol are better molecules for skin gene expression compared to S-equol and the percutaneous absorption of equol represents a unique epidermal reservoir delivery mechanism.
authors.affiliation: Department of Physiology, Developmental Biology and the Neuroscience Center, Brigham Young University , Provo, UT , USA.
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Lephart
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D060754:Equol / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D007536:Isomerism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D015595:Skin Aging / Q000187:drug effects*; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D003879:Dermatologic Agents; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D060754:Equol