Elucidating Wenshen Xuanbi Decoction's Anti-Osteoporotic Mechanisms via Integrated Multiomics Analysis

Area of Science:

• Integrative biology
• Pharmacology
• Genomics

Background:

• Primary osteoporosis (POP) is a significant health concern.
• Traditional Chinese Medicine (TCM) offers potential therapeutic strategies.
• Understanding the molecular mechanisms of TCM is crucial for clinical application.

Purpose of the Study:

• To elucidate the active components and therapeutic mechanisms of Wenshen Xuanbi Decoction (WSXBT) against primary osteoporosis (POP).
• To utilize an integrated multi-omics approach for comprehensive analysis.

Main Methods:

• High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-Q-TOF-MS/MS) for chemical constituent identification.
• Network pharmacology, transcriptomic profiling (GSE35958), single-cell RNA sequencing (GSE147287), and Weighted Gene Co-expression Network Analysis (WGCNA) for target identification.
• Molecular docking and dynamics simulations for binding confirmation.

Main Results:

• Identified 28 chemical constituents in WSXBT.
• Discovered 15 core targets for WSXBT against POP, with CTNNB1 and AKT1 as top candidates.
• Confirmed WSXBT modulates PI3K-AKT and Wnt signaling pathways, influencing cellular senescence and osteoclast differentiation.

Conclusions:

• WSXBT demonstrates anti-osteoporotic effects through multi-target modulation of PI3K-AKT and Wnt signaling pathways.
• The study provides a scientific foundation for WSXBT's clinical use in treating POP.
• Advances understanding of TCM's complex, multi-target therapeutic mechanisms.