Typologie d'actualités: CBM

Milk thistle, a plant extract with promising –green- medicinal properties against psoriasis

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

Bispidines and manganese: a winning couple

As an essential metal ion and an efficient relaxation agent, Mn2+ holds great promise as a substitute for Gd3+ in MRI contrast agent applications, if its stable and inert complexation can be achieved. To achieve this goal, the “Metal complexes and MRI” team of CBM and their collaborators from the University of Heidelberg, Germany, created a Mn2+ selective chelator by introducing four pyridine and one carboxylate donors on a bispidine skeleton. Thanks to a highly rigid and preorganized structure and perfect size-match for Mn2+, the new ligand L provides not only remarkably high thermodynamic stability, but also excellent selectivity over the major biological competitor Zn2+, as well as kinetic inertness. The unusual eight-coordinate structure of the Mn2+ complex, in contrast to the six-coordinate structure of the Zn2+ analogue, underlines that the coordination cavity is perfectly adapted for Mn2+, while it is too large for Zn2+. The MRI efficiency of this MnL complex is about 30% higher than that of typical Mn2+ systems. In vivo MRI experiments realized in control mice at a very low dose (0.02 mmol/kg) indicate good signal enhancement and fast renal clearance. Taken together, MnL is the first chelate that combines such excellent stability, selectivity, inertness and relaxation properties, all of primary importance for MRI use.

D. Ndiaye, P. Cieslik, H. Wadepohl, A. Pallier, S. Même, P. Comba, and É. Tóth, Mn2+ bispidine complex combining exceptional stability, inertness and MRI efficiency, J. Am. Chem. Soc. 2022, doi : 10.1021/jacs.2c10108
JACS spotlight sur cet article : https://pubs.acs.org/doi/pdf/10.1021/jacs.2c12719