Rehmannia Root Improves Extracellular Matrix Production and Epidermal Differentiation by Upregulation of the Estrogen Receptor

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.