Identification of major transcription factor regulating gene signautures associated with jakyakgamcho-tang in PC12 cells
Neuropathic pain (NP) is a chronic condition caused by complex molecular mechanisms. Due to the challenges in NP treatment, it is crucial to develop novel targeting strategies that can help elucidate its molecular mechanisms. Jakyakgamcho-tang (JGT) has significant therapeutic potential; however, its precise mechanism of action remains unclear. In this study, we systematically investigated the key transcription factors and mechanisms of action of water/ethanol extract of JGT (WJGT/EJGT) and their compounds using transcriptome analysis. We identified key transcription factor involved in NP pathogenesis by profiling transcriptome and histone ChIP-seq from NP model. We analyzed gene expression changes in PC12 cells treated with JGT extract to determine its key mechanisms and transcriptional regulators. To further validation the novel mechanisms and targets of JGT and its key compounds, we conducted in vitro experiments. The PDGFRB pathway was significantly downregulated by JGT extracts, with Fos identified as a key transcription factor regulating JGT-induced target gene expression. Furthermore, we identified key compounds among seven compounds that were regulated by the PDGFRB pathway and Fos expression. Notably, the targets modulated by JGT extracts and its key compounds were associated with inflammation. Our findings suggest that targeting the PDGFRB pathway and its key transcription factor, Fos, is a potential therapeutic strategy for NP. This study provides novel insights into the mechanism and transcriptional regulator underlying JGT and its key compounds in NP treatment. Overall design: Total whole transcritome profiles treated with water extract of Jakyakgamcho-tang (JGT) and  ethanol extract of JGT in PC12 cell.