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.

Xiaoxuming decoction cutting formula reduces LPS-stimulated inflammation in BV-2 cells by regulating miR-9-5p in microglia exosomes

“…This study also detected components in XXMD-C, including ephedrine, pseudoephedrine, cinnamaldehyde, baicalin, baicalein, wogonin, and ginsenoside Rg1, which can represent the four Chinese medicinal materials in XXMD-C. Many components in XXMD-C, such as ephedrine ( Zheng et al, 2012 ; Wu et al, 2014 ; Wei et al, 2019 ; Sioud et al, 2020 ), pseudoephedrine ( Li et al, 2019 ), cinnamaldehyde ( Liu et al, 2019 ; Kim et al, 2020 ; Gulec Peker and Kaltalioglu, 2021 ), baicalin ( Li et al, 2020 ; Fu et al, 2021 ; Yan et al, 2021 ), and ginsenoside Rg1 ( Chen et al, 2022 ; Zhang et al, 2022 ), have been reported in relevant literature to have significant anti-inflammatory effects. Therefore, it can be seen that XXMD-C indeed has anti-inflammatory potential.…”

Nephroprotective effect of Ginsenoside Rg1 in lipopolysaccharide-induced sepsis in mice through the SIRT1/NF-κB signaling

“…Rg1 is the main active component of Panax ginseng and has many pharmacological properties [34]. In recent years, the protection afforded by Rg1 has been confirmed in sepsis [35] and sepsis-related diseases, including septic acute lung injury [36], septic cardiac dysfunction [37], and septic encephalopathy [38]. Additionally, several studies have demonstrated the beneficial role of Rg1 in many types of experimental models of renal disorders, such as obstructive nephropathy [39] and unilateral ureteral obstruction [40].…”

Traditional herbs: mechanisms to combat cellular senescence

“…In addition, ginsenoside Rb1 improves inflammation in the heart, kidneys, and nervous system. In the nervous system, ginsenoside Rg1 can improve murine microglia and brain type I astrocytes damage through the NF-κB/TLR4 inflammatory signaling pathway and the p38/JNK-MAPK signaling pathway [225,226]. In a spinal cord injury and cognitive impairment-based study in rats, ginsenoside Rb1 improves injury and cognitive impairment via NRF2 and PI3K/AKT inflammatory signaling pathways [227,228].…”