Abstract
Despite the known beneficial impacts of estrogen used as hormone replacement therapy to ameliorate signs of skin aging in postmenopausal women, its compliance rates are low. A significant amount of estrogen may be absorbed into the blood circulation and can lead to systemic actions. Soy isoflavone exhibits biological activities similar to synthetic estrogen because it is a heterocyclic phenolic compound. The disadvantage of most topical ingredients based on isoflavone is that they contain biologically inactive glycoside forms, which must be converted to a readily absorbed aglycone for the topical application. The purposes of this study were to develop niosomes-loaded Aspergillus oryzae-fermented soybean extract (FSE) to enhance skin absorption with proven systemic side effect compared to estrogen application. Skin hydration and viscoelasticity of 75 days post-ovariectomized (OVX) Wistar rats following 84-day topical treatment with various tested gel formulations containing fermented soybean extract (FSE) were evaluated. The tested formulations were gel + FSE nanoniosomes, gel + FSE microniosomes, gel + FSE (200 µg FSE/9 cm2/rat), gel + blank nanoniosomes (a negative control), and gel + 17β-estradiol (E2) nanoniosomes (a positive control, 20 µg E2/9 cm2/rat). Changes in vaginal cornifications and weights of uteri, livers, and kidneys in the OVX rats and signs of primary skin irritation in the rabbits were evaluated for their toxicities. Results showed that FSE-loaded nanoniosomes improved the skin hydration and viscoelasticity better than gel + FSE microniosomes and gel + FSE, respectively, but lower than those of gel + E2 nanoniosomes (p < 0.05). Unlike all gel + E2 nanoniosomes, the FSE formulations showed no changes in vaginal cells and weights of uteri, livers, and kidneys and no signs of skin irritation. In conclusion, The FSE niosome-based gels should be promising candidates for delivering phytoestrogens against signs of skin aging with no systemic toxicities.
Highlights
Since estrogen plays a significant role in the modulations of skin physiology, insufficient estrogenic levels during post-menopausal physiological changes result in the reduction of dermal and epidermal cellularity and collagen quantity [1]
Fermentation of soybean with A. oryzae for 10 days showed near completion in the conversion of isoflavone glycosides into their corresponding aglycones (Figure 1b)
Kuiper at al. [40] suggested that the estrogenic activity of phytoestrogens depended on their affinity for ERs
Summary
Since estrogen plays a significant role in the modulations of skin physiology, insufficient estrogenic levels during post-menopausal physiological changes result in the reduction of dermal and epidermal cellularity and collagen quantity [1]. Replacement Therapy (HRT) of 17β-estradiol applied orally or topically can ameliorate signs of skin aging by increasing skin elasticity and hydration, reducing wrinkles and collagen synthesis [3,4,5]. Despite the positive effects of estrogen as HRT in managing menopausal symptoms and reversing skin physiology, there remains controversy over its long-term health risks and connection to breast cancer [6]. Despite the well-documented use of soy isoflavone as a dietary health supplement administered orally, long-term consumption of isoflavones may associate with potential carcinogenic and immunosuppressive effects raise concerns. Applied isoflavone is an interesting pathway to bypass such systemic risk; there is still a limited use for skin application [8,9]
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