PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice

Sun, Chaofen; Zhang, Chenyu; Duan, Jia‐Xi; Guan, Xin‐Xin; Yang, Huihui; Jiang, Huiling; Hammock, Bruce D.; Hwang, Sung Hee; Zhou, Yong; Guan, Cha‐Xiang; Liu, Shao-Kun; Zhang, Jun

doi:10.1016/j.bbrc.2019.12.131

Cited by 38 publications

(41 citation statements)

References 36 publications

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“…A novel dual COX-2/sEH inhibitor (PTUPB) inhibits debris-stimulated ovarian tumor growth by preventing an eicosanoid and cytokine surge of pro-inflammatory and pro-angiogenic mediators ( Gartung et al, 2019 ). PTUPB inhibits high-fat diet-induced non-alcoholic fatty liver disease via inhibition of fibrosis, collagen deposition and pro-inflammatory cytokines ( Sun et al, 2020 ). sEH is a therapeutic target as it is upregulated in obesity-induced colonic inflammation and sEH inhibition reduces obesity-induced activation of Wnt signaling in mice ( Wang et al, 2018 ).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

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129

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

Self Cite

129

View full text Add to dashboard Cite

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“…Western blotting was performed as described previously [83]. The antibodies used were as follows: rabbit anti-β-actin antibody (1:2000, Proteintech, Wuhan, China), rabbit anti-α-SMA antibody (1:1000, Proteintech, Wuhan, China), rabbit anti-SIRT1 (1:1500, Proteintech, Wuhan, China), rabbit anti-NOX4 antibody (1:1000, Proteintech, Wuhan, China), rabbit anti-NRF2 antibody (1:1500, Proteintech, Wuhan, China), rabbit anti-phospho-AKT (Ser473) antibody (1:2000, Cell Signaling), rabbit anti-phospho-AMPK (Thr172) antibody (1:1000, Cell Signaling), rabbit anti-AMPK antibody (1:1000, Proteintech, Wuhan, China).…”

Section: Western Blotting Analysismentioning

confidence: 99%

Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling

Zou

Chen

Sun

et al. 2021

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.

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“…Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by steatosis of liver parenchyma and excessive accumulation of lipid in hepatocytes. The pathogenesis of the NAFLD is closely associated with obesity, hyperlipidemia, and insulin resistance (Anavi et al, 2017 ; Zheng et al, 2018 ; Sun et al, 2020 ; Wang et al, 2020 ). The treatment of NAFLD is challenging in clinical settings due to the lack of knowledge on the complete mechanism underlying its pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Gardenoside Hinders Caspase-1-Mediated Hepatocyte Pyroptosis Through the CTCF/DPP4 Signaling Pathway

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD)is accompanied by typical inflammatory damage and cell death. As a pro-inflammatory form of cell death, pyroptosis participates in important pathological processes involved in NAFLD. Regulatory roles of both CCCTC-binding factor (CTCF) and dipeptidyl peptidase-4 (DPP4) have been reported in NAFLD, but it is still unclear whether the mechanism of action of gardenoside, a potential therapeutic for NAFLD, can be driven via these proteins. In this study, the direct interaction between CTCF and DPP4 was first confirmed by a dual-luciferase reporter assay system. Then, a cell model of NAFLD was established by induction with palmitic acid (PA) and lipopolysaccharide (LPS). A mouse NAFLD model was established, and the effect of gardenoside on both the cell and mouse models of NAFLD was also investigated. Increased lipid accumulation, NLRP3 inflammasome activation, and hepatocyte pyroptosis were recorded in NAFLD in vitro and in vivo. Gardenoside treatment effectively reduced the lipid accumulation, increased cell viability, reduced reactive oxygen species (ROS) generation, and attenuated pyroptosis and apoptosis in NAFLD in the in vitro and in vivo models. Alterations in these biological processes were evidenced by the decreased expression levels of several pro-pyroptotic markers including the NLR family, pyrin domain-containing 3 (NLRP3), apoptosis-related speckle-like protein (ASC), caspase-1 p20, Gasdermin D N-terminal domain (GSDMD-N), and IL-1β, along with simultaneously decreased CTCF and DPP4 levels. Importantly, CTCF silencing or DPP4 silencing exhibited effects similar to gardenoside treatment, while CTCF overexpression counteracted this trend, which indicated that CTCF might be a target responsible for gardenoside-induced alleviation of NAFLD, such therapeutic effects might be achieved through controlling the expression of the direct target of CTCF (DPP4) and several downstream molecules. In general, the current study provides a promising strategy for NAFLD treatment.

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PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice

Cited by 38 publications

References 36 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling

Gardenoside Hinders Caspase-1-Mediated Hepatocyte Pyroptosis Through the CTCF/DPP4 Signaling Pathway

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