Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

Mol Med Rep. 2021 Dec;24(6):859. doi: 10.3892/mmr.2021.12499. Epub 2021 Oct 19.

Abstract

Psoriasis, a chronic inflammatory skin disease, is characterized by the excessive proliferation and impaired differentiation of epidermal keratinocytes and is accompanied by the increased infiltration of inflammatory cells. The condition requires long‑term treatment and has no definitive cure. Hence, supplements and therapeutic agents have been intensely investigated. Gomisin M2 (GM2), a lignan extracted from Schisandra chinensis (Turcz). Baill. (Schisandraceae; S. chinensis), has demonstrated diverse pharmacological properties, including anticancer, anti‑inflammatory and antiallergic effects. Based on these findings, the present study examined the effects of GM2 on an imiquimod (IMQ)‑induced psoriasis mouse model and on keratinocytes stimulated by tumor necrosis factor (TNF)‑α and interferon‑γ. IMQ was topically applied to the back skin of mice for 7 consecutive days, and the mice were orally administered CD. These results showed that the oral administration of GM2 suppressed the symptoms of psoriasis, as evidenced by reductions in skin thickness, psoriasis area severity index scores for psoriasis lesions, transepidermal water loss and myeloperoxidase (MPO)‑associated cell infiltration. Furthermore, GM2 reduced the pathologically increased levels of immunoglobulin G2a, MPO and TNF‑α in the serum and T helper (Th)1 and Th17 cell populations in the spleen. GM2 decreased the gene expression of inflammatory‑related cytokines and chemokines and inhibited the expression of signal transducer and activator of transcription 1 and nuclear factor‑κB in the activated keratinocytes. These results suggested that GM2 from S. chinensis is a potential therapeutic candidate to alleviate psoriasis‑like skin inflammation.

Keywords: Th1/Th17 cells; gomisin M2; keratinocytes; myeloperoxidase; psoriasis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Line
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Female
  • Humans
  • Imiquimod / toxicity
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interferon-gamma / toxicity
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Th1 Cells / drug effects
  • Th17 Cells / drug effects
  • Tumor Necrosis Factor-alpha / toxicity

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Lignans
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tumor Necrosis Factor-alpha
  • gomisin M2
  • Interferon-gamma
  • Imiquimod

Grants and funding

This work was supported by the National Research Foundation of Korea grants funded by the Korean government (grant nos. 2019R1C1C1005172, 2019R1A2B5B01069444, 2019M3A9H1103690, 2017M3A9G8083382 and 2020M3A9D3038894).