ABSTRACT
This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.
Subject(s)
Animals , Male , Rats , Plant Extracts/pharmacology , Lindera/chemistry , Gastrointestinal Microbiome/drug effects , Inflammation/prevention & control , Liver/ultrastructure , Liver Diseases, Alcoholic/prevention & control , Lipopolysaccharides/blood , Cytokines/blood , Rats, Sprague-Dawley , Protein Serine-Threonine Kinases/blood , Plant Roots/chemistry , Disease Models, Animal , Toll-Like Receptor 4/blood , Liver Diseases, Alcoholic/diagnostic imagingABSTRACT
The consumption of alcohol causes several liver-associated diseases all over the world. Alcoholic liver diseases (ALD) include hepatic inflammation, fatty liver, hepatitis, liver cirrhosis and fibrosis and finally hepatocellular carcinoma. Although the cellular, metabolic and biochemical mechanisms for these diseases are quite explicable, the roles of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are still under investigation. The present review describes the roles and regulation of MMPs and TIMPs in different ALDs along with the involvement of other pathways. This review also summarizes the present knowledge on clinical and experimental trials with different antioxidants that help against alcohol associated liver diseases.