A Network Pharmacology Approach to Uncover the Molecular Targets and Associated Potential Pathways of Lycii Fructus for the Treatment of Retinitis Pigmentosa

Abstract

Objective: To explore the molecular targets and associated potential pathways of Lycii Fructus (LF, Gou Qi Zi, 枸杞子) in the treatment of retinitis pigmentosa (RP) by the approaches of network pharmacology and bioinformatics. Methods: The potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). RP-related gene targets were retrieved through disease comprehensive databases. Protein-protein interaction (PPI) network of LF component-targets and RP disease-targets was constructed by STRING, and the intersection of the 2 networks was extracted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of theintersection network were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID). CytoHubba was used to screen the key targets. Results: A total of 188 chemical constituents related to LF was retrieved from TCMSP database. 45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability (OB) and drug similarity (DL). 36 active ingredients were further screened and 201 targets related to these constituents were obtained. 206 target genes directly related to RP were obtained from the disease comprehensive databases, and 89 genes were obtained from the intersection of component-target and disease-target PPI network. These genes were mainly involved in intracellular signal transduction, GTPase activity regulation, cell morphology regulation, and other biological processes. Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity, GTPase activator activity, receptor signal protein serine/threonine kinase activity and so on. They were enriched in the cytoplasm, cell membrane, Golgi apparatus, and other regions. The mechanism was related to cell cycle pathways, neurotrophin signaling pathways, Ras signaling pathways, and so on. 10 key gene targets of LF in the treatment of RP were screened. Conclusions: The material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol, mandenol, and so on. The key targets of LF in the treatment of RP include 10 genes, such as Rho, PAK, and so on. The main mechanism is related to the regulation of the Ras signaling pathway, neurotrophin signaling pathway, cell cycle related pathway, and other signaling networks. Keywords: Network pharmacology, Retinitis pigmentosa, Lycii Fructus (Gou Qi Zi, 枸;杞;子;), Molecular mechanism, Target, Signaling pathway