Molecular insights into the role of Estrogen Receptor Beta in Ecdysterone Mediated Anabolic Activity

作者：Syeda Sumayya Tariq, Madiha Sardar, Muhammad Shafiq, Heather Heinz, Mohammad Nur-e-Alam, Aftab Ahmed, Zaheer Ul‐Haq · 发表于：PLoS ONE · 年份：2025 · DOI：10.1371/journal.pone.0320865 · 被引用次数：4 · 研究领域：Neurobiology and Insect Physiology Research、Free Radicals and Antioxidants、Computational Drug Discovery Methods

Ecdysterone, often dubbed a "natural steroid," has garnered significant attention among athletes for its reputed growth-promoting and anabolic properties. Unlike synthetic anabolic steroids, which are classified as controlled substances, ecdysteroids remain largely unregulated in many countries and are widely marketed as dietary supplements. Notably, ecdysterone has been included in the World Anti-Doping Agency (WADA) monitoring program, highlighting its potential impact on athletic performance and raising questions about its regulation. Emerging evidence indicates that, unlike traditional anabolic steroids that act primarily via the Androgen Receptor (AR), ecdysterone's anabolic effects may be mediated through Estrogen Receptors (ERs), particularly Estrogen Receptor beta (ERβ). Despite these insights, the precise molecular mechanisms underlying ecdysterone's biological activity remain poorly characterized, particularly from an in-silico perspective. This paper aims to address these gaps by exploring ecdysterone's mechanism of action through computational and molecular modeling approaches. This study employs an advanced computational framework to unravel the binding dynamics and interaction mechanisms of ecdysterone with Androgen Receptor (AR), Estrogen Receptor alpha (ERα), and Estrogen Receptor beta (ERβ). Using chemical descriptor analysis, inter-molecular interaction mapping, and all-atom molecular dynamics simulations spanning 250 ns for each system, the study reveals th...