ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1563275

This article is part of the Research TopicMetabolic dysfunction-associated fatty liver disease (MAFLD): Innovative Management strategies using Herbal MedicinesView all 6 articles

Bletilla striata polysaccharides ameliorate metabolic-associated fatty liver disease by decreasing the NLRP3 inflammasome and pyroptosis

Provisionally accepted
Tingting  YuTingting Yu1Juan  XueJuan Xue2Wenqian  TangWenqian Tang3Xiaojie  WuXiaojie Wu1Jun  LiJun Li1Fan  YangFan Yang3*Lei  LuoLei Luo3*
  • 1Hubei University of Chinese Medicine, Wuhan, Hubei Province, China
  • 2Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Wuhan, Hubei Province, China
  • 3Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

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. 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. 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. The results demonstrate that 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. In conclusion, BSP-1 may represent a promising therapeutic agent for MASLD treatment by inhibiting the NLRP3/caspase-1/GSDMD signaling pathway.

Keywords: Bletilla striata polysaccharide, metabolic-associated fatty liver disease, nod-like receptor protein 3, pyroptosis, Inflammasome

Received: 21 Jan 2025; Accepted: 11 Jun 2025.

Copyright: © 2025 Yu, Xue, Tang, Wu, Li, Yang and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Fan Yang, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, Hubei Province, China
Lei Luo, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, Hubei Province, China

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