Dihydromyricetin Alleviates Non-Alcoholic Fatty Liver Disease by Modulating Gut Microbiota and Inflammatory Signaling Pathways

Abstract

IntroductionNon-alcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases globally, characterized by widespread hepatocellular steatosis unrelated to alcohol or other explicit liver injury factors [1].As a complex chronic multisystem disorder, the occurrence and progression of NAFLD are influenced by various factors, including genetic predisposition, environmental elements, individual metabolic status, and intestinal microbiota balance [2].Often coexisting with other metabolic disorders such as type 2 diabetes mellitus, hypertension, and hypercholesterolemia, NAFLD manifests systemic metabolic disturbances with common symptoms like abnormal glucose tolerance and dyslipidemia [3].Furthermore, liver function in NAFLD patients may deteriorate gradually, leading to non-alcoholic steatohepatitis (NASH), liver fibrosis, and potentially cirrhosis and hepatocellular carcinoma [4].The prevalence of NAFLD is steadily rising due to the global increase in lifestyle-related diseases such as obesity and diabetes [5].Due to its widespread impact, the prevention and management of NAFLD are crucial in clinical practice and integral to global public health policies [6,7].Although current treatment methods primarily focus on lifestyle adjustments such as increasing physical activity, modifying the dietary structure, and weight reduction, these measures are often challenging to sustain long-term and have limited efficacy [8][9][10].Therefore, in-depth research on NAFLD can aid in understanding its complex pathogenic mechanisms and facilitate the development of more effective preventive and intervention strategies, ultimately enhancing patients' quality of life and reducing the incidence of related complications [11].Recent studies have revealed a strong association between intestinal flora and chronic metabolic diseases such as NAFLD and diabetes [12].The intestinal microbial structure and composition in NAFLD patients and mice show significant alterations compared to healthy individuals [13,14].By modulating the intestinal flora in NAFLD mouse models, researchers have observed improvements in maintaining intestinal barrier function and Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition that is strongly linked to gut microbiota imbalance and chronic inflammation.This study aims to explore the preventive effects of dihydromyricetin (DHM) on NAFLD by modulating the intestinal flora and the TLR4/NF-B signaling pathway.Fifty male C57BL/6J mice were randomly assigned to five groups: a normal control group, a model group, and three DHM treatment groups receiving low (500 mg/kg), medium (750 mg/kg), and high doses (1,000 mg/kg).NAFLD was induced using a high-fat diet, and DHM was administered for 8 weeks.ELISA measured serum levels of LPS, IL-1, and TNF-, while Western Blot assessed liver expression of TLR4 and NF-B p65.Changes in intestinal flora composition were analyzed using high-throughput 16S rRNA sequencing.The results showed that DHM treatment significantly reduced serum levels of LPS, IL-1, and TNF-, decreasing the liver expression of TLR4 and NF-B p65.Intestinal flora analysis indicated a notable increase in beneficial bacteria, especially in the medium and high-dose groups.DHM treatment also significantly improved liver pathology, reducing fat deposition and inflammatory cell infiltration.In conclusion, DHM effectively prevents the progression of NAFLD by improving gut microbiota balance and suppressing inflammatory signaling pathways.

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