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Background:
The role of nucleotide-binding oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome and pyroptosis in the inflammatory microenvironment of metabolic-associated fatty liver disease (MASLD) has been posited as crucial. Bletilla striata polysaccharides (BSPs), extracted from the tubers of Bletilla striata (Thunb.) Rchb.f. , exhibit significant anti-inflammatory properties. However, their potential protective effects on MASLD and their role in regulating pyroptosis remain unclear.
Objectives:
This study investigates the efficacy of BSP-1, a purified metabolite isolated from crude BSPs, on MASLD by evaluating its ability to modulate the NLRP3/caspase-1/GSDMD signaling pathway.
Methods:
To simulate MASLD in vivo and in vitro , high-fat diet (HFD)-induced rat models and free fatty acid (FFA)-stimulated HepG2 cells were used. Serum indicators and histopathological staining were employed to assess liver injury and lipid deposition. Additionally, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB) analysis were conducted to examine the NLRP3/caspase-1/GSDMD pathway and related cytokine levels.
Results:
BSP-1 significantly ameliorates alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels in both rat serum and HepG2 cells. Furthermore, BSP-1 reduces inflammatory factors interleukin (IL)-1β and IL-18, while improving pathological changes in rat liver tissue. Mechanistically, BSP-1 regulates the expression of pyroptosis-related proteins and mRNAs in the NLRP3/caspase-1/GSDMD pathway, thereby protecting against MASLD.
Discussion:
BSP-1 may represent a promising therapeutic agent for MASLD treatment by inhibiting the NLRP3/caspase-1/GSDMD signaling pathway.
Details
Caspase-1;
Antibodies;
High fat diet;
Alanine transaminase;
Anti-inflammatory agents;
Pyroptosis;
Fatty liver;
Cytokines;
Cholesterol;
Metabolism;
Chromatography;
Liver diseases;
Animal models;
Apoptosis;
Enzyme-linked immunosorbent assay;
Oligomerization;
Proteins;
Inflammation;
Aqueous solutions;
Pyrin protein;
Polysaccharides;
Immunofluorescence;
Inflammasomes;
Hydrochloric acid;
Aspartate aminotransferase;
Biotechnology industry;
Immunohistochemistry;
Tumor necrosis factor-TNF;
Molecular weight;
Liver cirrhosis;
Pathogenesis;
Metabolites;
Signal transduction;
Western blotting;
Bletilla striata
1 School of Clinical Medical, Hubei University of Chinese Medicine, Wuhan, China
2 Department of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China
3 Department of Health Management Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China