In silico investigation of Aloe vera phytoconstituents targeting key proteins involved in atopic dermatitis progression
TL;DR
Quercetin and kaempferol from A. vera emerge as promising multitarget lead candidates for AD treatment, particularly for topical therapeutic applications, and warrant further in vitro and in vivo validation to support their potential clinical translation.
Abstract
Background Atopic dermatitis (AD) is a chronic inflammatory skin disease involving complex immune pathways. Natural compounds derived from Aloe vera are attracting increasing attention for their potential in the treatment of dermatological disorders. Materials and methods A virtual screening of 110 A. vera-derived phytoconstituents was performed against three key protein targets implicated in AD: interleukin-4 receptor alpha, Janus kinase 1, and phosphodiesterase 4D. The top-ranked compounds were further assessed using absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties to evaluate drug-likeness and safety profiles. Molecular dynamics (MD) simulations over 100 ns were conducted to examine the structural stability of the selected ligand–protein complexes. Results Quercetin and kaempferol showed the highest binding affinities across all three targets. ADMET analysis confirmed their favorable pharmacokinetic and safety profiles. MD simulations revealed stable and compact protein–ligand interactions, supporting their potential as multitarget inhibitors of AD. Conclusions Quercetin and kaempferol from A. vera emerge as promising multitarget lead candidates for AD treatment, particularly for topical therapeutic applications. These findings warrant further in vitro and in vivo validation to support their potential clinical translation.