Abstract
Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma.
Highlights
The skin is a barrier that separates the body from the external environment and plays essential roles in regulating water loss and protecting the body from ultraviolet radiation and microbial infection [1]
We found that sudachi peel extract (SPE) suppressed epidermal growth factor (EGF)-induced cell proliferation through inhibition of the extracellular regulated kinase (ERK) pathway in the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes
These results show that SPE possesses antiproliferation and pro-differentiation activities in epidermal keratinocytes, and that it may have the potential for treating skin diseases, such as psoriasis and cutaneous squamous cell carcinoma (cSCC), by improving the abnormalities of proliferation and differentiation in keratinocytes
Summary
The skin is a barrier that separates the body from the external environment and plays essential roles in regulating water loss and protecting the body from ultraviolet radiation and microbial infection [1]. The citrus peel waste of the juice extraction process contains phytochemicals such as vitamins, minerals, flavonoids, coumarin, limonoids, carotenoids, and pectin, which possess a variety of biological functions including antioxidant, anti-inflammatory, antimutagenic, anticarcinogenic, and antiaging properties [11]. It has potential for use in the food, cosmetic, and pharmaceutical industries. We revealed that SPE enhanced calcium-induced keratinocyte differentiation of HaCaT cells and primary keratinocytes These results show that SPE possesses antiproliferation and pro-differentiation activities in epidermal keratinocytes, and that it may have the potential for treating skin diseases, such as psoriasis and cSCC, by improving the abnormalities of proliferation and differentiation in keratinocytes
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