The Effects of the Major Phytochemicals of Salvia miltiorrhiza on the Serine Protease KLK-5 in Rosacea: In Silico Screening and Molecular Dynamics Simulation

Year 2025, Volume: 84 Issue: 1, 87 - 102, 05.06.2025

Sümeyye Durmaz , Esma Ulusoy

https://doi.org/10.26650/EurJBiol.2025.1597573

Abstract

Objective: Rosacea is a chronic inflammatory skin disorder in which kallikrein-5 (KLK-5) plays a crucial role in disease progression. Targeting KLK-5 inhibition is a promising therapeutic strategy. Regarding rosacea's complex mechanisms and pathophysiology, KLK-5 plays a key role in the immune dysregulation pathway. The pathophysiology of rosacea may begin with an aberrant innate immune response, marked by overexpressed and over-activated KLK-5, which increases the expression of Toll-like Receptor 2 and MMP-9. The cleavage of larger precursor peptides into LL-37 leads to inflammation.

Materials and Methods: This study investigated the major phytochemicals of Salvia miltiorrhiza as potential KLK-5 inhibitors through molecular docking, ADME-Tox analysis, and molecular dynamics (MD) simulations. Docking studies assessed the binding interactions of S. miltiorrhiza phytochemicals with KLK-5 (PDB ID: 6QFE), comparing them to a native ligand (GSK144) and the clinically used azelaic acid.

Results: Azelaic acid exhibited the weakest binding affinity, whereas danshensu, tanshinone I, and tanshinone IIA demonstrated stronger interactions with KLK-5. The ADME-Tox analysis identified danshensu as the most promising candidate owing to its favorable pharmacokinetic and toxicity profiles. MD simulations further confirmed the stability of the danshensu-KLK-5 complex, showing minimal structural fluctuations and supporting its inhibitory potential.

Conclusion: These findings indicate that danshensu is a promising candidate for KLK-5 inhibition in rosacea, suggesting the need for further studies to validate its therapeutic potential.

Keywords

Rosacea , Salvia miltiorrhiza , Molecular Docking , ADME-Tox , Molecular Dynamics Simulation , ComputerAided Drug Design

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