ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1593689
This article is part of the Research TopicTreating Hepato-Intestinal Diseases with Herbal Medicines and their MetabolitesView all 5 articles
Polysaccharide of Atractylodes macrocephala Koidz alleviate LPSinduced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis
Provisionally accepted
Xiaoxiao Chen1Shuzhan Yang2Xin Long1Wanyan Li1Bingxin Li1
Cheng Fu1
Cao Xue Zhen1
Danning Xu1
Xinliang Fu1*
Nan Cao1*- 1Zhongkai University of Agriculture and Engineering, Guangzhou, China
- 2Technology Center of Guangzhou Customs, Guangzhou, China
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Pyroptosis is a distinctive form of inflammatory cell death, mediated by the activation of the inflammasome, which initiates a potent inflammatory response. Long non-coding RNAs (lncRNAs) modulate pyroptosis by targeting microRNAs and their target genes through a competing endogenous RNA (ceRNA) mechanism. Our previous research has confirmed that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) can alleviate inflammatory liver injury in mice caused by lipopolysaccharide (LPS), but the specific molecular mechanism remains unclear. Additionally, recent studies have identified recruited macrophages in the liver as a key component of both acute and chronic liver inflammation. This study aimed to explore the impact of PAMK on LPS-induced macrophage pyroptosis and its molecular mechanism in mitigating inflammatory liver injury in mice.Methods: C57BL/6 mice were subjected to LPS-induced liver injury with or without PAMK pretreatment. Histopathological analysis, qRT-PCR, Western blot, and ELISA were performed to assess liver damage and pyroptosis markers. In RAW264.7 macrophages, dual-luciferase assays validated ceRNA interactions, while gain/loss-of-function experiments elucidated molecular mechanisms.In this study, we found that PAMK alleviated LPS-induced inflammatory liver injury in mice and modulates macrophage pyroptosis through the lncRNA GAS5/miR-223/NLRP3 axis.We conclude that there is a ceRNA relationship between GAS5, miR-223-3p, and NLRP3; PAMK alleviates LPS-induced pyroptosis in macrophages through the lncRNA GAS5/miR-223-3p/NLRP3 axis; and PAMK intervention in the macrophage pyroptosis process subsequently alleviates liver inflammation.
Keywords: pyroptosis, Polysaccharide of Atractylodes macrocephala Koidz, liver inflammation, macrophage, ceRNA
Received: 14 Mar 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Chen, Yang, Long, Li, Li, Fu, Zhen, Xu, Fu and Cao. 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:
Xinliang Fu, Zhongkai University of Agriculture and Engineering, Guangzhou, China
Nan Cao, Zhongkai University of Agriculture and Engineering, Guangzhou, China
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