Using Network Pharmacology and Transcriptome Sequencing to Investigate the Mechanism of Action of Luteolin and Quercetin in Treating Obesity

ABSTRACT Luteolin and quercetin, which are flavonoids, are present in various traditional Chinese medicines. Although they have been shown to improve obesity, the specific mechanisms of action remain unclear. This study aimed to determine pivotal targets and major regulatory pathways involved in their mechanisms of action using network pharmacology and transcriptome sequencing. Data on luteolin/quercetin‐related targets were acquired from the PharmMapper platform, and data on known obesity‐related targets were collected from the OMIM and GeneCards databases. Differentially expressed genes (DEGs) involved in luteolin and quercetin action that regulate adipogenic differentiation were identified using RNA sequencing (RNA‐seq). Bioinformatic analyses were performed to identify potential target genes and pathways regulated by luteolin/quercetin during adipogenesis. Finally, key genes and pathways were validated through quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting. Network pharmacology showed that luteolin/quercetin was closely associated with anti‐obesity targets. The related pathways were metabolic, PI3K/AKT, and MAPK pathways. RNA‐seq revealed 91 common DEGs involved in luteolin/quercetin regulation of adipogenic differentiation. Finally, nine potential target genes (including CIDEC, Mgll, Slc2a4, Pck1, and PNPLA3) were identified, and the AMPK and AKT signaling pathways were verified. The present study provides novel information regarding the molecular mechanism of luteolin and quercetin action in treating obesity and demonstrates their therapeutic effects through multiple targets and pathways.