Anti-inflammatory effect of ginsenoside Rg1 on LPS-induced septic encephalopathy and associated mechanism.

Abstract

BACKGROUND Sepsis frequently occurs in patients after infection and is highly associated with death. Septic encephalopathy is characterized by dysfunction of the central nervous system, of which the root cause is a systemic inflammatory response. Sepsis-associated encephalopathy is a severe disease that frequently occurs in children, resulting in high morbidity and mortality. OBJECTIVES In the present study, we aim to investigate the neuroprotective mechanism of ginsenoside Rg1 in response to septic encephalopathy. METHODS Effects of ginsenoside Rg1 on septic encephalopathy were determined by cell viability, cytotoxicity, ROS responses, and apoptosis assays and histological examination of brain. Inflammatory activities were evaluated by expression levels of IL-1β, IL-6, IL-10, TNF-α, and MCP-1 using qPCR and ELISA. Activities of signaling pathways in inflammation were estimated by the production of p-Erk1/2/Erk1/2, p-JNK/JNK, p-p38/p38, p-p65/p65, and p-IkBα/IkBα using western blot. RESULTS LPS simulation resulted in a significant increase in cytotoxicity, ROS responses, and apoptosis and a significant decrease in cell viability in CTX TNA2 cells, as well as brain damage in rats. Moreover, the production of IL-1β, IL-6, IL-10, TNF-α, and MCP-1 was significantly stimulated both in CTX TNA2 cells and in the brain, which confirmed the establishment of vitro and in vivo models of septic encephalopathy. The damage and inflammatory responses induced by LPS were significantly decreased by treatment with Rg1. Western blot analyses indicated Rg1 significantly decreased the production of p-Erk1/2/Erk1/2, p-JNK/JNK, p-p38/p38, p-p65/p65, and p-IkBα/IkBα in LPS-induced CTX TNA2 cells and in the brain. CONCLUSIONS These findings suggested that Rg1 inhibited the activation of NF-κB and MAPK signaling pathways, which activate the production of proinflammatory cytokines and chemokines. The findings of this study suggest that ginsenoside Rg1 is a candidate treatment for septic encephalopathy.