Ginsenoside Compound K Reduces Psoriasis-related Inflammation by Activation of the Glucocorticoid Receptor in Keratinocytes.

To investigate the effects and mechanism of Ginsenoside Compound K (GCK) on psoriasis, focusing on the glucocorticoid receptor (GR) in keratinocytes. An imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was generated to evaluate the anti-inflammatory effect of GCK. Hematoxylin and eosin (H&E) staining was used to assess skin pathological changes. Protein expression of K17 and p-p65 in mice skin was assayed by immunohistochemical. Protein expression and phosphorylation of p65 IκB were assayed by Western blot. Protein expression of K1, K6, K10, K16, K17, and GR were assayed by Western blot and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels of TNF-α, IL-6, CXCL-8, and ICAM-1. Real-time polymerase chain reaction (RT-PCR) was used to quantify TNF-α, IL-6, IL-8, and ICAM-1 mRNA expression. Cell viability was determined by Cell Counting Kit-8(CCK-8) assay. A high-content cell-imaging system was used to assay cell proliferation. Nuclear translocation of p65 and GR was assayed by imaging flow cytometry and immunofluorescence microscopy. Small interfering RNA was used to confirm the role of GR in the anti-inflammatory and immunoregulatory effect of GCK in normal human epidermal keratinecytes (NHEKs). GCK reduced the psoriasis area, severity index, and epidermal thickening in IMQ-induced mice. GCK significantly attenuated the mRNA levels of IL-6, IL-8, TNF-α, and ICAM-1 and reduced epidermal hyperproliferation in the skin of IMQ-induced mice. GCK inhibited in vitro activation of NF-κB, leading to attenuated release of inflammatory mediators (IL-6, IL-8, TNF-α, and ICAM-1) and suppression of NHEK hyperproliferation and abnormal differentiation. These inhibitory effects of GCK were diminished by GR silencing in NHEKs. GCK suppressed psoriasis-related inflammation by suppressing keratinocyte activation, which may be related to promoting GR nuclear translocation and inhibiting NF-κB activation. In summary, GCK appears to be a GR activator and a promising therapeutic candidate for antipsoriatic agents.

Wang W ，Xu X ，Yang M ，Jiang M ，Wang D ，Tang C ，Wei W ，Chen J ... -  《-》

Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice.

Gao J ，Chen F ，Fang H ，Mi J ，Qi Q ，Yang M ... -  《-》

Glycyrrhizin ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice and inhibits TNF-α-induced ICAM-1 expression via NF-κB/MAPK in HaCaT cells.

Glycyrrhizin (GL) is an important derivative of certain herbal medicines used in Asian countries. Currently, GL is used to treat hepatitis and allergic disease worldwide because of its anti-viral and anti-allergy effects. In addition to these prominent functions, GL likely regulates cellular functions such as tumor cell growth and cellular immunity. However, how GL affects the keratinocyte inflammation response remains poorly understood. The current paper investigates the effect of GL on psoriasis and explores the mechanisms involved. We used an in vitro cell model of tumor necrosis factor (TNF)-α-induced keratinocyte inflammation and the topical application of imiquimod (IMQ) using an animal model (mouse skin) of IMQ-induced psoriasis-like inflammation (IPI) to investigate the effect of GL on skin inflammation. Cell viability was analyzed using the Cell Counting Kit-8 (CCK8). Carboxyfluorescein succinimidyl ester (CFSE) labeling was used to trace monocyte adherence to keratinocytes. A Western blot analysis was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) and the activation of the nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling pathway. A modified version of the Psoriasis Area Severity Index (PASI) was used to monitor disease severity. Hematoxylin and eosin (H&E) staining was used to observe pathological changes. An immunohistochemistry (IHC) analysis was used to detect ICAM-1 expression in mouse skin. GL treatment significantly reduced the levels of ICAM-1 in TNF-α-stimulated HaCaT cells, inhibited subsequent monocyte adhesion to keratinocytes, and suppressed the nuclear translation and phosphorylation of p65 following the degradation of inhibitor κB (IκB). GL treatment blocked the phosphorylation of extracellular signal-regulated kinase (ERK)/p38 MAPK. GL effectively delayed the onset of IPI in mice and ameliorated ongoing IPI, thereby reducing ICAM-1 expression in epidermal tissues. These results demonstrate that GL treatment ameliorates skin inflammation by inhibiting ICAM-1 expression via interference with the ERK/p38 MAPK and NF-κB signaling pathways in keratinocytes. Therefore, GL can be used as an anti-psoriasis drug.

Xiong H ，Xu Y ，Tan G ，Han Y ，Tang Z ，Xu W ，Zeng F ，Guo Q ... -  《-》

Astragaloside IV suppresses the proliferation and inflammatory response of human epidermal keratinocytes and ameliorates imiquimod-induced psoriasis-like skin damage in mice.

Liu T ，Ai L ，Jiang A ，Wang Y ，Jiang R ，Liu L ... -  《-》

Experimental study on the effect of luteolin on the proliferation, apoptosis and expression of inflammation-related mediators in lipopolysaccharide-induced keratinocytes.

Wang X ，Yao Y ，Li Y ，Guo S ，Li Y ，Zhang G ... -  《-》