Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

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.

Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF

“…The following 12 hub genes were shared between the adipose tissue and the heart: ADRA1A (adrenoceptor alpha 1A), CCNF (cyclin F), CCR1 (C–C motif chemokine receptor 1), EGFR (epidermal growth factor receptor), MLYCD (malonyl-CoA decarboxylase), NRAS (NRAS proto-oncogene, GTPase), NSTR1 (neurotensin receptor 1), PRKCD , PTGFR (prostaglandin F receptor), SKP1 (S-phase kinase-associated protein 1), TTBK2 (tau tubulin kinase 2), and YKT6 ( Ykt6 v-Snare homolog). These hub genes can activate the calcium signaling pathway and promote the dysfunction of the heart and adipose tissue ( Huang and Chen, 2008 ; Li et al, 2008 ; Ye et al, 2014 ; Kao et al, 2015 ; Kuchay et al, 2017 ; Wang M. et al, 2018 ; Abe et al, 2020 ; da Silva Rosa et al, 2020 ; Esteves et al, 2020 ; Wu L. et al, 2020 ). CCR1 , which was downregulated in the adipose tissue but significantly upregulated in the heart, is directly associated with more than 10 other genes in the two tissues.…”

“…Tissue-specific hub genes were shaped with round rectangle and labeled with blue. Kuchay et al, 2017;Wang M. et al, 2018;Abe et al, 2020;da Silva Rosa et al, 2020;Esteves et al, 2020;. CCR1, which was downregulated in the adipose tissue but significantly upregulated in the heart, is directly associated with more than 10 other genes in the two tissues.…”

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis

“…Hub genes of the four common signaling pathways were analyzed and WNT1, AKT3, DVL1, CCND1, HIST1H2BO, JUN, EGFR, RAC1, ACTN1 and ACTN2 were screened out. These hub genes are primarily involved in the processes of cell proliferation and differentiation (24)(25)(26)(27)(28)(29)(30)(31). Some genes are also reported to be involved in the formation of osteoclasts (32,33).…”