Abstract:

We used the Gene Expression Omnibus database to identify targets associated with chronic obstructive pulmonary disease (COPD) and heart failure(HF). Then, we explored the chemical composition and targets of Fritillaria thunbergii-Trichosanthis fructus to determine their potential to regulate COPD complicated by HF. We analyzed the target function and pathway annotation to create a network of tissue-specific protein-protein interactions (PPI).A total of 227 targets were involved in regulating COPD complicated by HF progression through Fritillaria thunbergii-Trichosanthis fructus, including 153 upregulated and 74 downregulated genes.Topological analysis showed that the average median of the PPI network was 0.4, and the average degree value was 1.83, with key targets including RPS23, SNU13, NOL6, ELAVL1. The cellular components were mainly located in the endomembrane system, nuclear endosomes, and extracellular vesicles. Biological processes mainly involved vesicle-mediated transport, microtubule-based motility, and intracellular protein transport.The relevant signaling pathway was the MAPK signaling pathway.MCODE analysis revealed two core clusters: Cluster 1 involves genes such as TKT,ENO1, NCL, and KIF1B, which are involved in regulating the Golgi transport of kinesin and estrogen, and Cluster 2 involves genes such as SIN3B, PHF20, CTBP1, and XPNPEP1, which are involved in the regulation of histone-associated responses.Tissue-specific PPI networks in the auricles, left ventricle, and lungs suggest that the Fritillaria thunbergii-Trichosanthis fructus pairing may affect the progression of COPD complicated by HF through the regulation of the ELAVL1-ENO1-NCL axis.Molecular docking showed that the binding of trichosanic acid, the main active ingredient involved in relieving the chest and dispersing mass, and peimisine, the main ingredient involved in dissipating phlegm and dispersing mass, to the protein targets ELAVL1, ENO1, and NCL was highly stable, and that the binding of peimisine to said three target proteins was stronger than that of trichosanic acid.This indicates that the combination of the two ingredients is first used to treat the lungs and then to regulate the heart, and that they are mutually necessary, resulting in therapeutic effects on both the heart and lungs.

Key words: Fritillariae Thunbergii Bulbus, Trichosanthis Fructus, chronic obstructive pulmonary disease, heart failure, systems pharmacology