title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Guozhen
authors.initials: G
authors.lastname: Tan
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Han
authors.forename: Zengqi
authors.initials: Z
authors.lastname: Tang
authors.forename: Wenying
authors.initials: W
authors.lastname: Xu
authors.forename: Fanqin
authors.initials: F
authors.lastname: Zeng
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019695:Glycyrrhizic Acid; D020928:Mitogen-Activated Protein Kinases; D000077271:Imiquimod