Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

Zhang, Yizhe; Zhang, Shujie; Luo, Xin; Zhao, Han; Xiang, Xiaoxing

doi:10.1590/acb361106

Cited by 3 publications

(1 citation statement)

References 30 publications

(22 reference statements)

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“…Paeoniflorin could reduce cholestatic inflammation and liver fibrosis in the PBC mouse model by eliminating mtROS through the SIRT1/forkhead box O1 (FOXO1)/superoxide dismutase 2 (SOD2) signaling pathway, and thereby alleviate mitochondrial damage and inhibit NLRP3 inflammasome activation (185)(186)(187).…”

Section: Nlrp3 Inhibitorsmentioning

confidence: 99%

Inflammasome and pyroptosis in autoimmune liver diseases

et al. 2023

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Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

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Section: Nlrp3 Inhibitorsmentioning

confidence: 99%

Inflammasome and pyroptosis in autoimmune liver diseases

et al. 2023

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Oxyberberine suppressed the carbon tetrachloride-induced liver fibrosis by inhibiting liver inflammation in a sirtuin 3-dependent manner in mice

Zhao

Xing

et al. 2023

International Immunopharmacology

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Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-κB/HIF-1α Pathway in CCl₄-Induced Liver Fibrosis

Liu

Yang

et al. 2023

Am. J. Chin. Med.

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Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

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Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

Cited by 3 publications

References 30 publications

Inflammasome and pyroptosis in autoimmune liver diseases

Inflammasome and pyroptosis in autoimmune liver diseases

Oxyberberine suppressed the carbon tetrachloride-induced liver fibrosis by inhibiting liver inflammation in a sirtuin 3-dependent manner in mice

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-κB/HIF-1α Pathway in CCl₄-Induced Liver Fibrosis

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Paeoniflorin mitigates PBC-induced liver fibrosis by repressing NLRP3 formation

Cited by 3 publications

References 30 publications

Inflammasome and pyroptosis in autoimmune liver diseases

Inflammasome and pyroptosis in autoimmune liver diseases

Oxyberberine suppressed the carbon tetrachloride-induced liver fibrosis by inhibiting liver inflammation in a sirtuin 3-dependent manner in mice

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-κB/HIF-1α Pathway in CCl4-Induced Liver Fibrosis

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Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-κB/HIF-1α Pathway in CCl₄-Induced Liver Fibrosis