Title:Ginsenoside Compound K Reduces Psoriasis-related Inflammation by
Activation of the Glucocorticoid Receptor in Keratinocytes
Volume: 17
Author(s): Wu Wang, Xiujin Xu, Mei Yang, Mengya Jiang, Dandan Wang, Caihong Tang, Wei Wei*Jingyu Chen*
Affiliation:
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, China
- Collaborative Innovation Center of Anti-inflammatory and Immune Medicines, Rheumatoid Arthritis Research Center, Anhui Medical University,
Hefei, Anhui, 230032, China
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, China
- Collaborative Innovation Center of Anti-inflammatory and Immune Medicines, Rheumatoid Arthritis Research Center, Anhui Medical University,
Hefei, Anhui, 230032, China
Keywords:
Ginsenoside compound K, Psoriasis, Keratinocytes, Glucocorticoid receptor, Nuclear factor kappa-B, Anti-inflammation.
Abstract:
Aim:
To investigate the effects and mechanism of Ginsenoside Compound K (GCK) on psoriasis, focusing on the glucocorticoid receptor (GR) in
keratinocytes.
Methods:
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).
Results:
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.
Conclusion:
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.
