Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis
IntroductionPyroptosis 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...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1593689/full |
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| author | Xiaoxiao Chen Shuzhan Yang Xin Long Wanyan Li Bingxin Li Cheng Fu Caoxue Zhen Danning Xu Xinliang Fu Nan Cao |
| author_facet | Xiaoxiao Chen Shuzhan Yang Xin Long Wanyan Li Bingxin Li Cheng Fu Caoxue Zhen Danning Xu Xinliang Fu Nan Cao |
| author_sort | Xiaoxiao Chen |
| collection | DOAJ |
| description | IntroductionPyroptosis 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.MethodsC57BL/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.ResultsIn 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.ConclusionWe 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. |
| format | Article |
| id | doaj-art-b3370c5d64224aa1993cb41b71918e2c |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-b3370c5d64224aa1993cb41b71918e2c2025-08-20T02:46:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15936891593689Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axisXiaoxiao Chen0Shuzhan Yang1Xin Long2Wanyan Li3Bingxin Li4Cheng Fu5Caoxue Zhen6Danning Xu7Xinliang Fu8Nan Cao9College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaGuangzhou Customs, Technology Center, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaCollege of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, ChinaIntroductionPyroptosis 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.MethodsC57BL/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.ResultsIn 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.ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1593689/fullpyroptosispolysaccharide of Atractylodes macrocephala Koidzliver inflammationmacrophageceRNA |
| spellingShingle | Xiaoxiao Chen Shuzhan Yang Xin Long Wanyan Li Bingxin Li Cheng Fu Caoxue Zhen Danning Xu Xinliang Fu Nan Cao Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis Frontiers in Pharmacology pyroptosis polysaccharide of Atractylodes macrocephala Koidz liver inflammation macrophage ceRNA |
| title | Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis |
| title_full | Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis |
| title_fullStr | Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis |
| title_full_unstemmed | Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis |
| title_short | Polysaccharide of Atractylodes macrocephala Koidz alleviate LPS-induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating LncRNA GAS5/miR-223-3p/NLRP3 axis |
| title_sort | polysaccharide of atractylodes macrocephala koidz alleviate lps induced inflammatory liver injury by reducing pyroptosis of macrophage via regulating lncrna gas5 mir 223 3p nlrp3 axis |
| topic | pyroptosis polysaccharide of Atractylodes macrocephala Koidz liver inflammation macrophage ceRNA |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1593689/full |
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