A Molecular-Dynamics-Guided Screening Pipeline Identifies Topical Glucocorticoid Receptor Modulators with Selective...

Area of Science:

• Dermatology
• Pharmacology
• Computational Biology

Background:

• Topical corticosteroids are standard psoriasis treatments but cause skin atrophy.
• Safer, steroid-sparing topical therapies are needed.
• Glucocorticoid receptor (GR) is key in skin health, but natural phytochemical activators are unexplored.

Purpose of the Study:

• To systematically explore phytochemicals for selective glucocorticoid receptor (GR) activation.
• To develop a computational framework for prioritizing natural compounds for topical pharmacology.

Main Methods:

• Utilized molecular modeling (docking, molecular dynamics, pharmacophore conservation) to assess four phytochemicals' GR engagement.
• Compared computational predictions with immunohistochemical analysis of GR in psoriatic skin specimens.

Main Results:

• Salvianolic acid B and lithospermic acid showed high GR docking affinity and stable binding.
• Lithospermic acid significantly increased GR phosphorylation at Ser211, indicating differential signaling.
• Computational and histological data showed preliminary concordance.

Conclusions:

• Integrating molecular modeling with histological analysis aids in identifying natural compounds with GR-engagement potential.
• This framework offers a reproducible strategy for prioritizing compounds in topical pharmacology.
• Supports future research into phytochemicals for dermatologic conditions.