Astragaloside IV ameliorate acute alcohol-induced liver injury in mice via modulating gut microbiota and regulating NLRP3/caspase-1 signaling pathway

Abstract

Purpose Astragaloside IV (AS-IV) is a natural saponin substance extracted from the plant Radix Astragali with anti-inflammatory, antioxidant, anti-apoptotic, and liver-protecting effects. This study was to evaluate the liver protection effect of AS-IV on mice after acute alcohol stimulation. Materials and Methods Mice were orally administrated with AS-IV (50, 150, and 500 mg/kg, respectively), and sodium carboxymethyl cellulose (CMC, 50 mg/kg) daily for 7 days, before giving five alcohol-intragastric injections. Results Results suggested that the levels of serum ALT and AST, liver SOD, GSH-PX, 4-HNE, and MDA, serum and liver TNF-α, IL-1β, and IL-6, serum lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), diamine oxidase (DAO) and Myeloperoxidase (MPO), the mRNA and protein expression of hepatic NLRP3, Caspase-1, IL-1β, and IL-18 were significantly decreased in AS-IV-treated mice compared with the model group. Moreover, the effect of AS-IV on histopathology of liver tissue confirmed its protective function. Furthermore, AS-IV ameliorated the gut microbiota imbalance and adjusted the abundance of the following dysfunctional bacteria closer to the control group: Butyricicoccus , Turicibacter , Akkermansia , Anaerotruncus , and Mucispirillum . A strong correlation between intestinal bacteria and potential biomarkers was found. Conclusion Together, our findings indicated that AS-IV exert the hepatoprotective effect by modulating the gut microbiota imbalance and regulating NLRP3/Caspase-1 signaling pathway.

Study on molecular mechanisms related to hepatic fibrosis by Mendelian randomization combined with transcriptome analysis

“…Butyric acid is a short-chain fatty acid that plays an important role in gut health and liver function. Butyricicoccus can inhibit pathogenic bacteria in the intestine, such as Escherichia coli, Salmonella, Clostridium perfringens, etc., and reduce the production and absorption of intestinal endotoxins, thus reducing the risk of liver inflammation and fibrosis 28 , which is consistent with the results of our study. These data open the exciting possibility of targeted intervention to modulate these taxa to modify disease progression in a precision medicine-based approach in future studies.…”

“…The datasets analyzed during the current study are available in the MiBioGen repository, https://mibiogen.gcc.rug.nl/ 28,29 , and the FinnGen repository, https://r9.finngen.fi/ 30,31 . All data generated or analyzed during this study are available from the corresponding author on reasonable request.…”

Progress in the Correlation Between Inflammasome NLRP3 and Liver Fibrosis

“… 68 Astragaloside IV can regulate gut microbiota imbalance, improve intestinal barrier function, inhibit the NLRP3/Caspase-1 inflammatory signaling pathway, and alleviate alcohol-induced liver inflammation. 69 Additionally, probiotics can enhance the intestinal mucus barrier by increasing the secretion of specific mucins. Probiotic intervention can help rebalance the gut microbiota and regulate intestinal barrier, thereby alleviating the liver damage.…”

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells

“…This, in turn, triggers a systemic inflammation reaction and damages various organs. Hence, identifying the specific targets of alcohol in the intestine is imperative to elucidate the underlying mechanism of ALD …”