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

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1468
Author(s):  
Shogo Abe ◽  
Misako Ueno ◽  
Mami Nishitani ◽  
Tetsuya Akamatsu ◽  
Takumi Sato ◽  
...  

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.

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Xue Mei Li ◽  
Kyung Eun Jung ◽  
Su Hyuk Yim ◽  
Dong Kyun Hong ◽  
Chang Deok Kim ◽  
...  

Autophagy, one mechanism of programmed cell death, is fundamental to cellular homeostasis. Previous studies have identified autophagy as a novel mechanism by which cytokines control the immune response. However, its precise role in immune-related inflammatory skin diseases such as psoriasis remains unclear. Thus, this study explored the functional role of autophagy in psoriatic inflammation of epidermal keratinocytes. Strong light chain 3 immunoreactivity was observed in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model, and it was readily induced by polycytidylic acid (poly (I:C)), which stimulates Toll-like receptor 3 (TLR3), in human epidermal keratinocytes in vitro. Rapamycin-induced activation of autophagy significantly reduced poly (I:C)-induced inflammatory reaction, whereas, inhibition of autophagy by 3-methyladeine increased that. Our results indicate that the induction of autophagy may attenuate TLR3-mediated immune responses in human epidermal keratinocytes, thus providing novel insights into the mechanisms underlying the development of inflammatory skin diseases including psoriasis.


1997 ◽  
Vol 52 (11-12) ◽  
pp. 817-823 ◽  
Author(s):  
Janina Gabrielska ◽  
Jan Oszmiańsk ◽  
Romuald Żyłka ◽  
Małgorzata Komorowska

Abstract Trihydroxyflavones of Scutellaria baicalensis, Antioxidant Activity, Liposome, Peroxidation, MDA The antioxidant effect of a trihydroxyflavone extract from Scutellaria baicalensis on oxida­ tion induced by ultraviolet light, was studied with phosphatidylcholine liposome membrane. Also, as standards, the antioxidative activity of baicalin, wogonin, baicalein and butylated hydroxytoluene (BHT) was investigated. Comparison of the protective effects of thecom­pounds studied against photoinduced lipid peroxidation in lecithin liposome membranes showed that: (1) the inhibitory effect of those compounds (at 1.2 mol% antioxidant content in liposomes) on TBA reactive materials from lipid peroxidation decreased in the order of baicalin > BHT ≅ Scutellaria baicalensis. These were found much greater than wogonin and baicalein; (2) the depressed effect of those compounds (at 1.1 mol% compounds content in liposomes) on the production of conjugated dienes (proportional to oxidation index) could be classified as follows: Scutellaria baicalensis ≅ baicalin > BHT, these three were found more active much greather than baicalein and wogonin. Results obtained by ESR measure­ment confirm that Scutellaria baicalensis extract and the BHT compound significantly de­ pressed the effect of liposome oxidation. It was found that the new trihydroxyflavones of Scutellaria baicalensis, ensured a very satisfactory concentration-dependent protection of the liposome membrane against UV-induced oxidation. These findings suggest that some of the beneficial effects of the extract of the Scutellaria baicalensis can be mediated in certain diseases (for example in skin diseases) by their ability to scavenge free radicals and by their protective effect on lipid peroxidation caused by sunlight irradiation.


Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 424
Author(s):  
Sajee Thaweekitphathanaphakdee ◽  
Pithi Chanvorachote ◽  
Sagaw Prateepchinda ◽  
Mattaka Khongkow ◽  
Apirada Sucontphunt

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.


Cosmetics ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 30 ◽  
Author(s):  
Peggy Schlupp ◽  
Thomas Schmidts ◽  
Axel Pössl ◽  
Sören Wildenhain ◽  
Gianni Lo Franco ◽  
...  

Olive trees (Olea europaea) and their processed products, such as olive oil, play a major role in the Mediterranean way of life. Their positive impact on human health is being intensely investigated. One research topic is the identification of new application areas of olive mill wastewater (OMWW). OMWW is characterized by the high content of polyphenols possessing many positive health effects. Thus, the phenol-enriched OMWW extract offers the potential for the treatment of skin disorders and for cosmetic application. The aim of the present study was to evaluate cell viability and proliferation, the anti-inflammatory and anti-oxidative properties of a phenol-enriched OMWW extract on an immortal keratinocyte cell line (HaCaT cells). Moreover, the influence on the growth of various microorganisms was investigated; furthermore, the effects on normal human epidermal keratinocytes (NHEK) and human melanoma cells (A375) were studied in a commercially available tumor invasion skin model. The phenol-enriched OMWW extract showed excellent antimicrobial activity. Moreover, a noticeable reduction in reactive oxygen species formation as well as Interleukin-8 release in HaCaT cells were observed. Finally, the inhibited growth of A375 melanoma nodules in the melanoma skin model could be shown. Our results indicate that the OMWW extract is a promising ingredient for dermal applications to improve skin health and skin protection as well as having a positive impact on skin ageing.


2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Luchun Yan ◽  
Hao Huang ◽  
Ying Zhang ◽  
Xinrong Yuan ◽  
Zhaohua Yan ◽  
...  

Abstract Colchicine, a plant-derived alkaloid with relatively low toxicity on normal human epidermal keratinocytes (HEKn), has selective inhibitory effect on the growth of CaSki (HPV16-positive) and HeLa (HPV18-positive) human cervical cancer cell lines via the induction of apoptosis. Colchicine (2.5, 5.0 and 10.0 ng/ml) significantly reduced the expression of human papilloma virus (HPV) 16 E6/E7 mRNA and protein in CaSki and HeLa cells. Moreover, reduced expression of E6 and E7 induced by Colchicine resulted in the up-regulation of tumor suppressor proteins, p53 and Rb, as well as down-regulation of phospho Rb (pRb) protein. In addition, Bax, cytosolic cytochrome c and cleaved caspase-3 protein were increased while Bcl-2 protein was decreased significantly by 48 h of Colchicine treatment. These results implied that Colchicine could be explored as a potent candidate agent for the treatment and prevention of HPV-associated cervical cancer without deleterious effects.


2018 ◽  
Vol 215 (2) ◽  
pp. 415-422 ◽  
Author(s):  
Rana Herro ◽  
Jr-Wen Shui ◽  
Sonja Zahner ◽  
Daniel Sidler ◽  
Yuko Kawakami ◽  
...  

Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT–HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT–HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.


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