Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin
Open accessAbstract
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.
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Equol stimulates gene expression of SH-rich detoxifying proteins metallothionein-1H and metallothionein-2H that protect against metal toxicity.
“equol has been shown to stimulate the gene expression of the SH-rich detoxifying proteins, like metallothionein-1H and metallothionein-2H, that protect against metal toxicity [85,94].”
Topical applications of equol have demonstrated improved human dermal parameters in in vitro, ex vivo, and in vivo studies.
“several reports using topical applications of equol have demonstrated improved human dermal parameters”
The epidermal reservoir delivery mechanism of topically applied equol to the dermal layer over time has not been seen with other compounds, such as resveratrol, genistein, or 17β-estradiol.
“Thus, the epidermal”
This sustained release of topically-applied equol acts upon fibroblasts and promotes continued positive effects on skin health and addresses oxidative stress.
“This sustained release of topically-applied equol acts upon fibroblasts and promotes continued positive effects on skin health and addresses the issues of oxidative stress [2,85].”
Franz cell testing using tritiated equol penetration into human skin has shown percutaneous absorption and skin content distribution among the epidermal and dermal compartments.
“Franz cell testing using tritiated equol penetration into human skin has shown: (1) the percutaneous absorption and; (2) skin content distribution among the epidermal and dermal compartments.”
Topically applied equol forms an epidermal reservoir that releases into the dermis with a primary absorption peak at approximately 8 h and a secondary peak at around 28 h.
“forms an equol”
More than 100,000 women have used topically-applied equol with great success.
“more than 100,000 women have used topically-applied equol with great success [2,78,84,85].”
Equol stimulates antioxidant enzymes SOD2 and TXNRD1 in human skin.
“From gene array studies, equol has been shown to stimulate the following antioxidant enzymes in human skin, such as SOD 2 and thioredoxin reductase 1 (TXNRD 1) [84,85].”
Only three genes displayed the greatest significant expression by S-equol, whereas 16 genes displayed the greatest significant levels by R-equol and/or racemic equol.
“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”
R-equol and/or racemic equol were more potent compared to S-equol in results for various human skin biomarkers.
“In general, R-equol and/or racemic were more potent compared to S-equol in the obtained results for various human skin biomarkers [85].”
Topical equol treatment in human skin via gene array studies demonstrated that interleukin levels (IL-1, IL-6, IL-8) and cyclo-oxygenase 1 (COX-1) were significantly inhibited.
“topical equol treatment in human skin via gene array studies have demonstrated that interleukin (IL) levels were significantly inhibited (such as IL-I, IL-6, IL-8 as well as cyclo-oxygenase 1 (COX-1)) [84,85].”
Tumor necrosis factor receptor levels were significantly inhibited by equol when compared to controls.
“tumor necrosis factor receptor levels were significantly inhibited by equol when compared to controls [84,85].”
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Self-citation
- Authors
- Lephart, E. D.
- Affiliations
- Brigham Young University (US)
- Corresponding author
- Lephart, Edwin D.
- ORCID
- Lephart, Edwin D.
- Venue
- Pharmaceutical Biology
- Publisher
- Informa UK Limited
- Published
- 2013-07-18
- Volume
- 51
- Issue
- 11
- Pages
- 1393-1400
- ISSN
- 0925-1618 (ISSN-L)
- 1388-0209
- 1744-5116
- OpenAlex
- W2029917165
- Cited by
- 37
- References
- 41
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 4
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmaceutical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham Young University
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- equol, S-equol, skin gene expression, type I collagen, human skin equivalents, human fibroblasts, percutaneous absorption, keratinocytes, extracellular matrix proteins, matrix metalloproteinases, inflammatory genes, isoflavonoids
- MeSH terms
- Administration, Cutaneous, Aged, Cells, Cultured, Dermatologic Agents, Female, Fibroblasts, Gene Expression Regulation, Humans, Isomerism, Male, Middle Aged, RNA, Messenger, Skin, Skin Absorption, Time Factors, Skin Aging, Keratinocytes, Extracellular Matrix Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Tissue Culture Techniques, Equol
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