Protective effects of equol and their polyphenolic isomers against dermal aging: microarray/protein evidence with clinical implications and unique delivery into human skin

Pharm Biol. 2013 Nov;51(11):1393-400. doi: 10.3109/13880209.2013.793720. Epub 2013 Jul 18.

Abstract

Context: 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.

Discussion and conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Cells, Cultured
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / chemistry
  • Dermatologic Agents / metabolism
  • Dermatologic Agents / pharmacology*
  • Equol / administration & dosage
  • Equol / chemistry
  • Equol / metabolism
  • Equol / pharmacology*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Humans
  • Isomerism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis*
  • RNA, Messenger / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Absorption
  • Skin Aging / drug effects*
  • Time Factors
  • Tissue Culture Techniques

Substances

  • Dermatologic Agents
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Equol