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.
Highlights
Alcohol has become a major pathogenic factor for liver disease [1]
This study aimed to determine the protective effect of an Linderae radix ethanol extract (LREE) on Alcoholic liver disease (ALD) model rats and whether this protective effect was related to the LPS-toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-kB) pathway
Rats were randomly separated into six groups: normal group (Normal, n=5, rats were intragastrically administered distilled water at 10 mL/kg body weight per day for 20 days, without any other treatment), model group (Model, n=5, ALD model rats without any treatment), positive control group (Essentiale group, n=5, ALD model rats were fed with Essentiale; 137 mg/kg, Sanofi-Aventis Beijing Pharmaceutical Co., Ltd., Chinese Medical University (China)), LREE high dose group (LGH group, n=5, ALD model rats fed with 4 g/kg LREE), LREE moderate dose group (LGM, n=5, ALD model rats fed with 2 g/kg LREE), and LREE low dose group (LGL, n=5, ALD model rats fed with 1 g/kg LREE)
Summary
Alcohol has become a major pathogenic factor for liver disease [1]. The pathogenesis of alcoholinduced liver injury involves the formation of reactive aldehydes free radicals resulting from ethanol metabolism [3]. Alcoholic liver disease (ALD) is a common cause of chronic liver injury, resulting from increased alcohol intake [4]. Patients with ALD frequently progress to liver fibrosis and cirrhosis, which have increased risks of complications, such as portal hypertension, and liver cancer [5]. The pathogenesis of ALD is complicated and unclear, which has led to the main cornerstone of ALD treatment being based only on lifestyle modification, including abstinence, nutritional therapy, and corticosteroid therapy.
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