Molecular Mechanisms of Crocin and Safranal in Appetite Regulation and Gut Microbiome Interaction: An In Silico and Network Pharmacology Study

Appetite regulation is a multifactorial process governed by central neuroendocrine signals, peripheral metabolic mediators, inflammatory pathways, and gut microbiome-derived metabolites. Among natural bioactive compounds, saffron phytochemicals—particularly crocin and safranal—have gained attention for their potential effects on satiety, mood, oxidative stress, inflammation, and metabolic homeostasis. However, the molecular basis of their appetite-regulatory actions remains insufficiently characterized. In the present study, an in silico network pharmacology framework was applied to explore the molecular mechanisms by which crocin and safranal may modulate appetite and gut microbiome interactions. Compound structures were retrieved from public chemical databases, and their putative protein targets were identified using target prediction platforms. Appetite-, obesity-, gut barrier-, and microbiome-related genes were collected from disease-gene databases and literature-based curation. The overlapping targets were analyzed using protein–protein interaction (PPI) networks, topological centrality assessment, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and compound–target–pathway network construction. In addition, molecular docking was performed against selected hub proteins involved in appetite signaling and gut–brain communication. The results identified a multi-target regulatory landscape involving serotonergic signaling, leptin and insulin resistance, AMPK and PPAR pathways, inflammatory cascades, intestinal barrier integrity, and microbial metabolite sensing. Key hub genes included AKT۱, TNF, IL۶, PPARG, SLC۶A۴, INS, LEP, MTOR, STAT۳, MAPK۳, and TP۵۳. Docking analysis suggested favorable binding of safranal to selected neuro-metabolic targets, whereas crocin demonstrated broader pathway-level relevance. Overall, these findings support saffron phytochemicals as network-based modulators with potential applications in appetite control, obesity management, and gut–brain axis regulation.

کلیدواژه ها:

Satiety signaling ، Gut–brain axis ، Host–microbiota crosstalk ، Neuroinflammation ، Metabolic homeostasis