Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis
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),...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1563275/full |
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| author | Tingting Yu Juan Xue Wenqian Tang Xiaojie Wu Jun Li Fan Yang Lei Luo |
| author_facet | Tingting Yu Juan Xue Wenqian Tang Xiaojie Wu Jun Li Fan Yang Lei Luo |
| author_sort | Tingting Yu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-700c2c77b0ee4323a1bbca0ebd74c342 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-700c2c77b0ee4323a1bbca0ebd74c3422025-08-20T02:36:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15632751563275Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosisTingting Yu0Juan Xue1Wenqian Tang2Xiaojie Wu3Jun Li4Fan Yang5Lei Luo6School of Clinical Medical, Hubei University of Chinese Medicine, Wuhan, ChinaDepartment of Gastroenterology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, ChinaDepartment of Health Management Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, ChinaSchool of Clinical Medical, Hubei University of Chinese Medicine, Wuhan, ChinaSchool of Clinical Medical, Hubei University of Chinese Medicine, Wuhan, ChinaDepartment of Health Management Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, ChinaDepartment of Health Management Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, ChinaBackground: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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1563275/fullBletilla striata polysaccharidemetabolic-associated fatty liver diseasenod-like receptor protein 3pyroptosisinflammasome |
| spellingShingle | Tingting Yu Juan Xue Wenqian Tang Xiaojie Wu Jun Li Fan Yang Lei Luo Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis Frontiers in Pharmacology Bletilla striata polysaccharide metabolic-associated fatty liver disease nod-like receptor protein 3 pyroptosis inflammasome |
| title | Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis |
| title_full | Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis |
| title_fullStr | Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis |
| title_full_unstemmed | Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis |
| title_short | Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis |
| title_sort | bletilla striata polysaccharides ameliorate metabolic associated fatty liver disease by decreasing the nlrp3 inflammasome and pyroptosis |
| topic | Bletilla striata polysaccharide metabolic-associated fatty liver disease nod-like receptor protein 3 pyroptosis inflammasome |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1563275/full |
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