Abstract
Estrogen is essential for the skin to maintain its physiological function. The binding of estrogen to the estrogen receptor (ER) activates gene transcription, which has biological effects on the target tissue. Estrogen levels and ER expression are known to decrease with aging and exposure to ultraviolet light (UV); therefore, increased estrogen levels and ER expression may improve age-related changes in the skin. Rehmannia root has been reported to have blood circulation-promoting and anti-inflammatory effects; however, few studies have reported the effects of Rehmannia root on skin. In this study, we examined the effects of Rehmannia glutinosa Libosch. var. purpurea Makino root extract (RE) on ER expression, and estrogen, RE, or their related ingredients increased ER expression in human epidermal keratinocytes, human dermal fibroblasts, and skin models. Moreover, RE increased the production of basic fibroblast growth factor, transforming growth factor β1, and epidermal growth factor. The mixture of estrogen and RE improved extracellular matrix (ECM) production to a greater degree than estrogen and RE independently. Although high population doubling levels (PDL) and UV irradiation downregulated ER expression, RE upregulated ER expression in high PDL cells and UV irradiated cells. In addition, RE increased the expression of epidermal differentiation marker proteins compared to their expression levels in the absence of RE. The collective findings suggest that RE aids in the prevention of skin aging by upregulating the ER expression that has been decreased by aging and UV and promoting estrogen activity, ECM production, and epidermal differentiation.
Highlights
Sex steroid hormones such as estrogen, progesterone, and androgen exhibit a broad spectrum of physiological functions ranging from regulating the menstrual cycle and reproduction to modulation of skin function, bone density, brain function, and cholesterol mobilization
The collective findings suggest that root extract (RE) aids in the prevention of skin aging by upregulating the estrogen receptor (ER) expression that has been decreased by aging and ultraviolet light (UV) and promoting estrogen activity, extracellular matrix (ECM) production, and epidermal differentiation
We evaluated the effect of ER upregulation on cell proliferation and determined that E2 did not affect cell proliferation, treatment with 80 μg/mL RE significantly promoted cell proliferation by upregulation of the ER
Summary
Sex steroid hormones such as estrogen, progesterone, and androgen exhibit a broad spectrum of physiological functions ranging from regulating the menstrual cycle and reproduction to modulation of skin function, bone density, brain function, and cholesterol mobilization. Binding of a ligand, such as estrogen and estrogen-like substances, activates the ER and promotes ER dimerization to produce homodimers of ERα or ERβ individually or the ERα-ERβ heterodimer. These dimers either bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors, such as activator proteins or specific proteins. The fibroblasts ER is involved in the proliferation of keratinocyte and epidermal formation, and the keratinocytes ER affects the increase of epidermal differentiation marker proteins such as loricrin, involucrin, and transglutaminase-1 as well as the proliferation of fibroblasts [10] [11] [12] These observations suggest that the balance of ER expression in each tissue is intimately involved in maintaining tissue homeostasis. Increases in estrogen levels and ER expression may improve the age-related changes in the skin; few studies have reported that ER expression is increased by crude drugs and cosmetic ingredients
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