Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.
Endoplasmic Reticulum Stress , Inflammation , Polysaccharides , Toll-Like Receptor 4 , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/antagonists & inhibitors , Polysaccharides/pharmacology , Polysaccharides/chemistry , Animals , Endoplasmic Reticulum Stress/drug effects , Mice , Inflammation/drug therapy , Inflammation/metabolism , Lymphocyte Antigen 96/antagonists & inhibitors , Lymphocyte Antigen 96/metabolism , Carthamus tinctorius/chemistry , Mice, Inbred C57BL , Molecular Structure , Dose-Response Relationship, Drug , Structure-Activity Relationship , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.
Diabetes Mellitus, Type 2 , Insulin Resistance , Non-alcoholic Fatty Liver Disease , Humans , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Lipogenesis , Zebrafish , Diabetes Mellitus, Type 2/metabolism , Liver/metabolism , Diet, High-Fat , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Lipids , Mice, Inbred C57BL , Forkhead Box Protein M1/metabolism
