Exploring the toxic effects of Kusnezoff Monkshood Root on respiratory diseases and analyzing its mechanism based on network toxicology and molecular docking technique: An in silico study

Respiratory diseases, such as lung injury and chronic obstructive pulmonary disease (COPD), significantly impact the quality of life and socio-economics of patients, and there is an urgent need for new therapeutic approaches and preventive measures. This study aimed to systematically analyze the toxic constituents of Kusnezoff Monkshood Root and their effects on the respiratory system through network toxicology and molecular docking techniques. We screened the active ingredients of Kusnezoff Monkshood Root from the TCMSP database and selected the active ingredient with the strongest toxic effect as the core research object. The TargetNet, SEA, and SwissTargetPrediction databases were used to collect potential targets of this active ingredient; GeneCards, TTD, and OMIM databases were used to search for respiratory toxic effect targets; and the intersection targets of the two were taken. The intersection targets were then used to construct a protein-protein interaction network through the STRING database, and then imported into Cytoscape software for visualization, and CytoNCA plug-in was used to find out the core targets, and finally the protein-protein interaction network analysis was carried out for the 5 core targets with the highest Degree values; and then the David database was used for the GO and OMIM analysis. Then, GO and KEGG analyses were carried out in David’s database; finally, the molecular docking technique was used to predict the relationship between the active ingredients and the core targets. Eight active ingredients with respiratory toxicity in Kusnezoff Monkshood Root were screened by the TCMSP database, and the most respiratory toxic component of Izoteolin was selected as the core research object. Finally, molecular docking analyses showed a strong affinity between Izoteolin and these core targets (binding energies ranging from −7.4 to −8.1 kcal/mol), suggesting a potential mechanism of action in respiratory toxicity and lung injury. In summary, this study reveals the toxic effects of Kusnezoff Monkshood Root on the respiratory system and provides a theoretical basis for future safety assessment of Kusnezoff Monkshood Root and the rules of dispensing, emphasizing the need for an in-depth understanding of the mechanisms of toxicity in the use of Chinese and Mongolian medicines.