RNA-Seq Analysis Reveals Potential Neuroprotective Mechanisms of Pachymic Acid Toward Iron-Induced Oxidative Stress and Cell Death

Abstract

Iron dysregulation is a crucial factor in the development of neurological diseases, leading to the accumulation of reactive oxygen species (ROS) and oxidative stress, triggering inflammatory responses, and ultimately causing neurological impairment. Pachymic acid (PA) is an active ingredient extracted from the medicinal fungus Poria cocos, which has been reported with multiple pharmacological effects, including anti-inflammatory, anti-ischemia/reperfusion, and anticancer actions. In this study, we test whether PA have neuroprotection effect aganist ferrous ions induced toxicity in SH-SY5Y cells. It was found that pre-treatment with PA reduced intracellular ROS levels, increased mitochondrial membrane potential, and protected cells from apoptotic death. RNA-seq and qRT-PCR results indicated that PA can regulate the key genes IL1B, CXCL8, CCL7, and LRP1 on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as NF-κB signaling pathway, IL-17 signaling pathway, to prevent Fe2+-induced apoptotic cell death. Our research indicated that PA has potential therapeutic effects on the neuroprotection by regulating neuroinflammation and oxidative stress damage.