Identification of components in scorpion and centipede traditional Chinese medicine formulations with potentially beneficial actions in asthma: network pharmacology and molecular docking.

Background: The aim of this study is to identify the principal active components of scorpion and centipede-derived traditional Chinese medicine (TCM) ingredients using network pharmacology and explore their mechanisms of action in the treatment of asthma.

Methods: The chemical constituents and target information pertaining to scorpion and centipede-derived TCM components were obtained from the Traditional Chinese Medicine System Pharmacology (TCMSP) database and an herbal database. Asthma-related target genes were retrieved from the GeneCards and the Online Mendelian Inheritance in Man (OMIM) databases. The "component-target" network was constructed with the identified target genes using "Cytoscape 3.9.2" software, and the protein-protein interaction (PPI) network was generated in conjunction with the String database to further identify the core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) functional enrichment analysis were carried out on the targets associated with scorpion and centipede-derived TCM components. Molecular docking was subsequently performed using Autodock Vina software to validate the results. Asthma mouse model was established, and mouse lung tissues were collected for histopathological examination. The levels of TP53, HSP90AA1, and IL-17 mRNA in the mouse lung tissues were evaluated.

Results: A total of 11 active components met the screening conditions, including 4 centipede-derived components and 7 scorpion-derived components. The key components identified included histamine, L-histidine, stearin, cholesteryl ferulate, and cholesterol, among others. Targets with degree values ≥ 16 included TP53, HSP90AA1, HSP90AB1, steroid receptor coactivator (SRC), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), and histone deacetylase 1 (HDAC1). The pathways involved comprised calcium signaling, estrogen signaling, arachidonic acid metabolism, inflammatory mediator and transient receptor potential (TRP) signaling, vascular smooth muscle contraction, thyroid hormone signaling, sphingolipid signaling, IL-17 signaling, insulin resistance, and human cytomegalovirus infection pathways. Furthermore, the mouse experiments showed that SC improved inflammatory cell infiltration and mucus secretion in mouse lung tissues and significantly suppressed the expression of TP53, HSP90AA1, and IL-17 mRNA (all p < 0.05).

Conclusion: Scorpion and centipede-derived active components may exert therapeutic effects in asthma treatment through potential targets such as TP53, HSP90AA1, HSP90AB1, SRC, EGFR, ESR1, MAPK1, MAPK3, and HDAC1.