Resveratrol, 4′ Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health

Abstract

Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4′ acetoxy resveratrol (4AR), R-equol, racemic equol or S-equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R-equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S-equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R-equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4′ analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R-equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin.

Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation

“…Since equol has a chiral carbon, it can exist as two isomers, S-equol and R-equol. Remarkably, S-equol binds ERβ approximately 1/5, as well as 17β-estradiol, while having low affinity for ERα [2,78,80]. For example, the Kd for 17β-estradiol has been reported at 0.15 nM for ERβ, while the Ki for S-equol was 0.7 nM as reported by Setchell at al.…”

“…Phenolics are a group of compounds having at least one hydroxyl group attached to an aromatic ring. The most high-profile polyphenolic molecule structurally related to equol known to the general public is resveratrol [2,77,78] (see Figure 3). In higher plants, thousands of molecules have polyphenolic structures that are thought to be involved in protecting plants against ultraviolet radiation, aggression by pathogens, or stress-related responses, such as drought, or other extreme environmental conditions, such as temperatures (heat or cold) [2,77,78].…”

“…Thus, equol (presumably S-equol) is present naturally in some plants, such as beans, cabbage, and lettuces, having a botanical origin [2,78,79] (see Figure 3). It also has chemical or biological properties, such as being a very strong antioxidant, the ability to bind specifically the potent androgen 5alpha-dihydrotestosterone (5α-DHT) with no affinity for a variety of other steroids, and it has an asymmetric carbon atom or chiral carbon that makes it structurally different from other polyphenolic compounds [2,78]. The asymmetric carbon is attached to four different atoms or groups of atoms, resulting in isomers or mirror image molecules that cannot be superimposed on each other [2] (see Figure 3).…”

“…Phyto-derived compounds from plants may have estrogenic characteristics because they can bind to mammalian estrogen receptors and to estrogen-related receptor gamma (ERR gama) [2,78] (see Figure 3). While endogenous estrogenic hormones, such as 17β-estradiol, are steroids with a cyclo-hexane-phenantrene parent chemical structure that is derived from cholesterol, equol is not a steroid.…”

“…For example, the Kd for 17β-estradiol has been reported at 0.15 nM for ERβ, while the Ki for S-equol was 0.7 nM as reported by Setchell at al. in 2005 and reviewed in 2017 [78,80]. Thus, S-equol is classified as a selective estrogen receptor modulator (SERM) with high affinity for ERβ.…”