# Pharmacological mechanism of active components in Polygonatum odoratum for idiopathic pulmonary fibrosis: a study integrating bioinformatics and experimental validation

## TL;DR

This study explores how Polygonatum odoratum may treat idiopathic pulmonary fibrosis by identifying key pathways and validating bioactive compounds.

## Contribution

The study integrates bioinformatics and experimental validation to reveal novel therapeutic mechanisms of Polygonatum odoratum for IPF.

## Key findings

- Central carbon metabolism and the PI3K-Akt pathway were identified as key pathways in IPF.
- MOL000332 (n-coumaroyltyramine) reduced fibrosis by suppressing EGFR, HIF1A, and GSK3B protein expression.
- Molecular docking confirmed strong binding of PO compounds to core targets like EGFR and MTOR.

## Abstract

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal interstitial lung disease characterized by persistent alveolar injury, inflammation, and extracellular matrix remodeling, ultimately leading to respiratory failure. Despite ongoing research, current therapeutic options for IPF remain limited, underscoring the urgent need for novel treatment strategies.

Methods: In this study, we investigated the pharmacological mechanisms of Polygonatum odoratum (PO) in treating IPF. We employed Weighted Gene Coexpression Network Analysis (WGCNA) and network pharmacology to identify potential therapeutic targets. Molecular docking and molecular dynamics simulations were conducted to evaluate the binding affinities and structural stability of key bioactive compounds. Subsequently, experimental validation was performed using a cellular model of bleomycin-induced pulmonary fibrosis.

Results: Network analysis identified central carbon metabolism and the PI3K-Akt signaling pathway as key associated pathways. Molecular docking demonstrated that bioactive compounds of PO (including MOL010412 and MOL000332) exhibited strong binding affinities to core targets such as EGFR, BCL2, MTOR, HIF1A, and GSK3B. Experimental results confirmed that MOL000332 (n-coumaroyltyramine) significantly mitigated pulmonary fibrosis by suppressing the protein expression levels of EGFR, HIF1A, and GSK3B.

Discussion: These findings suggested that PO exerted its therapeutic effects through the modulation of multiple targets and pathways, positioning it as a promising candidate for IPF treatment. This study provided a robust scientific foundation for further exploration and development of PO-based therapies for IPF.