Considering the relative low efficacy and high toxicity of current drug treatments against psoriasis, new therapeutic strategies are needed.
Scientists from CBM have searched for natural products unable to modulate the TGFb/miRNA-21-5p pathway in keratinocyte cells. This axis of regulation was chosen not only because it plays a pivotal role in epidermal haemostasis but also because its dysregulation is systematically associated with skin disorders including psoriasis.
To identify such bioactive compounds, a library of medicinal plant extracts was screened using the miR-ON RILES screening system placed under the control of the miRNA-21-5p in keratinocytes treated with TGFb. Silymarin, a mixture of flavonolignans extracted from Silybum marianum (L.) Gaertn., was identified as the most potent regulator of miRNA-21-5p expression. RNA-sequencing analysis revealed three unexpected transcriptomic signatures associated with keratinocyte differentiation, cell cycle, and lipid metabolism.
Mechanistically, Silymarin blocks cell cycle progression, inhibits keratinocyte differentiation through repression of Notch3 expression, stimulates lipid synthesis via activation of PPARg signaling and inhibits inflammatory responses by suppressing the transcriptional activity of NF-kB. Notably, the topical application of silymarin alleviates the development of psoriasiform lesions in mice by abrogating the altered expression levels of markers involved in inflammation, proliferation, differentiation, and lipid metabolism without inducing toxicity.
Therefore this plant extract might represent a promising "green" alternative to current pharmacological treatments for the management of this pathology.
Elodie Henriet,Florence Abdallah, Yoan Laurent, Cyril Guimpied, Emily Clement, Michel Simon, Chantal Pichon and Patrick BarilTargeting TGF-β1/miR-21 Pathway in Keratinocytes Reveals Protective Effects of Silymarin on Imiquimod-Induced Psoriasis Mouse ModelVolume 3, ISSUE 3, 100175, May 2023 - DOI:https://doi.org/10.1016/j.xjidi.2022.100175