Echinacoside: A potential therapeutic approach for alcohol-related liver disease by alleviating intestinal microbial dysbiosis, intestinal barrier dysfunction, and liver inflammation mediated by the endotoxin-TLR4/NF-κB pathway.

Alcohol-related liver disease (ALD) is one of the causes of chronic liver disease and a public health burden worldwide. Modulating the gut microbiota-hepatic immune loop is a key strategies for alleviate ALD. Echinacoside (ECH) is a natural phenylethanoidglycoside-structural compound that exerts significant anti-inflammatory, antioxidant, gut protective, and liver protective activities. However, as the therapeutic effect and mechanism of ECH in treating ALD remain unknown, this research aimed to investigate the impact of ECH on ALD and its potential mechanism. The intestinal damage, liver damage, and lipid accumulation in ALD mice were assessed by histological staining of tissue sections. The index of intestinal tight junction protein expression and the gut microbiota compositions were detected using molecular biology techniques and 16S rRNA sequencing analysis. The liver inflammation and oxidative stress levels were determined using enzyme assay indicators. Western blot analysis was used to measure the expression of proteins linked to the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalling pathway. The potential mechanism of TLR4 inhibition was studied further. The binding affinity of ECH with TLR4 was evaluated by molecular docking and analysing drug affinity reaction target stability. ECH treatment effectively improved the intestinal permeability and dysbiosis of ALD mice, improved liver oxidative stress injury and lipid accumulation, and mediated TLR4 regulation of liver inflammatory response. Overall, this study emphasizes the potential role of ECH in maintaining intestinal permeability, dysbiosis, and treating liver damage.