Advanced network pharmacology and molecular docking-based mechanism study to explore the multi-target pharmacological mechanism of Cymbopogon citratus against Alzheimer's disease

Alzheimer's disease (AD) is the most common type of dementia, accounting for at least two-thirds of cases of dementia in people age 65 and older. The limited amount of available data and multiple spectra of pathophysiological mechanisms of AD make it a challenging task and a serious economic load on the community health sector. Cymbopogon citratus is a tall perennial fast-growing grass with tuft of lemon-scented leaves from the annulate and sparingly branched rhizomes. A list of studies evidences the therapeutic efficacy of C. citratus against AD, but the precise molecular mechanism is yet to be discovered. This research utilizes network pharmacology and molecular docking approaches to elucidate the multi-target effects of C. Citratus on AD, identifying its active compounds, potential therapeutic targets, and associated signaling pathways. Initially the active compounds of C. citratus, the target genes related to both the C. citratus and the AD were retrieved from literature as well as databases. The PPI network of these target genes was constructed using STRING database and later the hub genes were screened by importing the network into the Cytoscape. The interactions among the target genes and the compounds were also analyzed using Cytoscape. The Gene Ontology (GO) and KEGG pathways of these hub genes were explored to reveal the genes involved in AD-related pathways. These compound-target, genes-pathway networks were explored which uncovered that bioactive compounds of C. citratus may serve as a magic bullet against AD by influencing the target genes involved in the disease pathogenesis. Further, the microarray data was analyzed to explore the expression level of core target genes. Lastly, docking analysis further strengthened the current findings by validating the effective activity of the bioactive compounds against putative target genes. Network pharmacology based analysis highlighted the pathways related to AD, the ten target genes, and the compounds involved in the AD disease mechanism. Through the analysis of microarray expression data, the two genes SRC and IL6 were found to have differential expression. Moreover, the molecular docking analysis predicted the string binding affinity among these genes and active compounds. In summary, our study proposed that five key compounds catechin, apigenin, 8-prenylnaringenin, quercetin, and luteolin contributed to the development of AD by affecting IL6 and SRC genes. The overall integration of network pharmacology with molecular docking unveiled the multi-target pharmacological mechanisms of C. citratus against AD. This study provides convincing evidence that C. citratus might partially alleviate the AD and ultimately lays a foundation for further experimental research on the anti-AD activity of C. citratus.