A tryptophol-containing emulgel ameliorates imiquimod-induced mice psoriasis

Sci Rep. 2025 Jun 3;15(1):19398. doi: 10.1038/s41598-025-04431-4.

Abstract

Tryptophol (TOH) is an aromatic alcohol, a natural compound, which is produced by various microorganisms. TOH has been reported to have sleep-inducing effects, anti-microbial activities as well as immunoregulatory properties. While TOH was shown to suppress proinflammatory cytokine production in a variety of cell types, in vivo evidence supporting the immunosuppressive effect of TOH remains sparse. Here, we report that TOH reduced the severity of skin inflammation in a mouse model of imiquimod (IMQ)-induced psoriasis. The results revealed that the TOH-containing emulgel decreased the pathological score of the psoriasis area and severity index (PASI). Topical administration of TOH-containing emulgel inhibited keratinocyte proliferation in IMQ-treated skin as indicated by reduced immunoreactivity for Ki67 and decreased mRNA expression of K6, K16 and K17. Skin of TOH-containing emulgel-treated IMQ mice displayed fewer Giemsa-positive cells and CD4+ cells than those of emulgel-treated IMQ mice, suggesting a decreased dermal infiltration of mast cells and CD4+ T cells, respectively. RT-qPCR results showed that interleukin (IL)-17A, IL-23 and IL-33 were downregulated in psoriatic skin of TOH-containing emulgel-treated IMQ mice. Western blot analysis demonstrated that phosphorylation of JAK2 and STAT3, downstream signaling molecules of IL-17A and IL-23, was decreased in TOH-containing emulgel-treated IMQ mice. Additionally, TOH-containing emulgel dermal application alleviated IMQ-induced splenomegaly and suppressed expression of TNFα, IL-1 and IL-6 in spleen and axillary lymph nodes. This study revealed that a TOH-containing emulgel attenuates IMQ-induced inflammation in psoriatic mice and could be a new therapeutic agent for managing psoriasis.

Keywords: Emulgel; Inflammation; JAK2/STAT3; Psoriasis; Tryptophol.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gels
  • Imiquimod* / adverse effects
  • Indoles* / administration & dosage
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Interleukin-17 / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • STAT3 Transcription Factor / metabolism
  • Skin / drug effects
  • Skin / pathology

Substances

  • Imiquimod
  • Indoles
  • Gels
  • Cytokines
  • STAT3 Transcription Factor
  • Interleukin-17