Rottlerin as a therapeutic approach in psoriasis: Evidence from in vitro and in vivo studies

PLoS One. 2017 Dec 22;12(12):e0190051. doi: 10.1371/journal.pone.0190051. eCollection 2017.

Abstract

Rottlerin is a natural polyphenolic compound that was initially indicated as a PKCδ inhibitor. However, it was recently revealed that it may target a number of molecules and have biological effects on various cell types and is considered as a possible agent for tumor and cell proliferative diseases. Psoriasis is a chronic inflammatory cutaneous disorder with undefined etiology and is characterized by abnormal cellular proliferation, angiogenesis, and inflammation. Therefore, this paper investigates the regulatory effects of rottlerin on normal human epidermal keratinocytes (NHEKs) and imiquimod (IMQ)-induced psoriasiform (IPI) lesions. In vitro results showed that rottlerin inhibited cell proliferation in NHEKs through growth arrest and NFκB inhibition. It may also induce apoptosis in an autophagy-dependent pathway. We found that rottlerin inhibited human microvascular endothelial cells tube formation on matrigel. Rottlerin also decreased the cell senescence of keratinocytes and intracellular ROS generation, which indicated its antioxidant effect. We also showed that rottlerin affects the expression of keratinocyte proliferation biomarkers. In 12-O-tetradecanoylphorbol13-acetate (TPA)-induced keratinocytes, rottlerin significantly inhibited the expression of the induced pro-inflammatory cytokines in keratinocytes. An animal experiment provided the corresponding evidence based on this evidence in vitro, by using IPI model, we found that rottlerin could relieve the psoriasiform of BALB/c mice by inhibiting keratinocyte proliferation, inflammatory cell infiltration, and vascular proliferation. In conclusion, our results suggest that rottlerin may prove useful in the development of therapeutic agents against psoriasis. However, the deep mechanism still requires further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / therapeutic use*
  • Adjuvants, Immunologic / therapeutic use
  • Adolescent
  • Adult
  • Aminoquinolines / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Benzopyrans / therapeutic use*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Imiquimod
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • NF-kappa B / metabolism
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Acetophenones
  • Adjuvants, Immunologic
  • Aminoquinolines
  • Benzopyrans
  • NF-kappa B
  • Reactive Oxygen Species
  • rottlerin
  • Imiquimod

Grants and funding

This research was supported by the grants from the National Natural Science Foundation of China (NSFC) (81371740, 81371741, 81630082, 81573039 and 91542124).