Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking

Abstract

Spinal cord injury (SCI) is characterized by high rates of disability and death. Valeriana jatamansi Jones (VJJ), a Chinese herbal medicine, has been identified to improve motor function recovery in rats with SCI. The study aimed to analyze the potential molecular mechanisms of action of VJJ in the treatment of SCI. The main ingredients of VJJ were obtained from the literature and the SwissADME platform was used to screen the active ingredients. The Swiss TargetPrediction platform was used to predict the targets of VJJ, and the targets of SCI were obtained from the GeneCards and OMIM databases. The intersecting genes were considered potential targets of VJJ in SCI. The protein–protein interaction network was constructed using the STRING database and the hub genes of VJJ for SCI treatment were screened according to their degree values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database. Cytoscape software was used to construct the “herb-ingredient-target-pathway” network. Preliminary validation was performed using molecular docking via Auto Dock Vina software. A total of 56 active ingredients of VJJ, mainly iridoids, were identified. There were 1493 GO items (P < .01) and 173 signaling pathways (P < .01) obtained from GO and Kyoto Encyclopedia of Genes and Genomes enrichment, including the phosphoinositide-3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, hypoxia-inducible factor 1 signaling pathway, and tumor necrosis factor signaling pathway. Molecular docking revealed that 12 hub genes enriched in the PI3K/Akt signaling pathway had a high binding affinity for the active ingredient of VJJ. VJJ may exert its therapeutic effects on SCI through the iridoid fraction, acting on signal transducer and activator of transcription 3, CASP3, AKT1, tumor necrosis factor, mammalian target of rapamycin, interleukin 6, and other hub genes, which may be related to the PI3K/Akt signaling pathway.

Iridoids rich fraction from Valeriana jatamansi Jones promotes axonal regeneration and motor functional recovery after spinal cord injury through activation of the PI3K/Akt signaling pathway

“…On the other hand, phosphorylated AKT promotes cytoskeletal filament assembly and axon growth ( Nieuwenhuis et al, 2020 ). Our prior research employing network pharmacology and molecular docking indicates a potential association between the therapeutic efficacy of IRFV in SCI rats and the PI3K/Akt signaling pathway ( Wang et al, 2023 ). In vivo , we found that the phosphorylation of Akt was upregulated in the spinal cord tissues of SCI rats treated with IRFV.…”

“…The principal chemical components of VJJ comprise iridoids, volatile oils, flavonoids, among others ( Jugran et al, 2019 ). Our prior network pharmacology research indicates that the predominant active constituents of VJJ effective in treating SCI are primarily iridoids ( Wang et al, 2023 ). Iridoids, classified as monoterpenes, typically exist in forms such as cyclopentanes and pyrans, and are extensively found across diverse plant and animal species ( Ndongwe et al, 2023 ).…”