Inhibition of oxidative stress and NLRP3 inflammasome by Saikosaponin-d alleviates acute liver injury in carbon tetrachloride-induced hepatitis in mice

Abstract

NLRP3 inflammasome activation results in severe liver inflammation and injury. Saikosaponin-d (SSd) possesses anti-inflammatory and hepatoprotective effects. This study aimed to determine the protective effects of SSd on carbon tetrachloride (CCl4)-induced acute liver injury in mice, and whether oxidative stress and NLRP3 inflammasome activation participate in the process. The CCl4 mice model and controls were induced. The mice were treated with SSd at 1, 1.5, or 2.0 mg/kg in a total volume of 100 µl/25 g of body weight. Liver injury was assessed by histopathology. Oxidative stress was determined using mitochondrial superoxide production (MSP), malondialdehyde (MDA) content, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. NLRP3, ASC, and Caspase 1 were determined by real-time PCR and western blot. IL-1β and IL-18 levels were determined by ELISA. Significantly elevated oxidative stress was induced in the liver by CCl4, as demonstrated by histopathology and increases of MDA and MSP levels and decreases of SOD, GPx, and CAT activities (all P < 0.01). SSd significantly decreased the MDA and MSP levels and increased the activities of SOD, GPx, and CAT (all P < 0.05). The mRNA expression of NLRP3, ASC, and Caspase 1, and the protein expression of Caspase 1-p10, NLRP3, ASC, IL-1β, and IL-18 were significantly increased after CCl4 induction (all P < 0.01). These changes were reversed by SSd (all P < 0.05). Suppression of the oxidative stress and NLRP3 inflammasome activation were involved in SSd-alleviated acute liver injury in CCl4-induced hepatitis.

Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway

“…Furthermore, studies have shown that SSd can inhibit the activation of HSCs by regulating intracellular inflammatory responses, thereby eventually inhibiting liver fibrosis ( Chen et al, 2013 ). Our previous studies also confirmed that SSd had a protective effect on CCl 4 -induced acute liver injury ( Chen et al, 2020 ). CCl 4 -induced chronic liver injury and liver fibrosis model mice were treated with SSd, and found that liver injury and liver fibrosis were significantly alleviated by SSd treatment compared with the control group.…”

Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway

“… 17 A study by Chen et al showed that SSD alleviated acute liver injury in carbon tetrachloride (CCl4)-induced hepatitis by suppressing oxidative stress and activation of the NLRP3 inflammasome. 18 Su etal demonstrated that SSD effectively improved lipopolysaccharide (LPS)-induced inflammation-related depressive behaviors. 19 However, the function of SSD in lytic bone disease remains unclear.…”

Hepatoprotective Effect of Mitochondria-Targeted Antioxidant Mito-TEMPO against Lipopolysaccharide-Induced Liver Injury in Mouse

“…mtROS levels in liver tissues of septic mice were measured by MitoSOX™ Red reagent (Thermo Fisher, USA) as described in a previous study [ 42 , 43 ]. Briefly, 5 μ M MitoSOX™ reagent working solution was prepared.…”