A COX-2/sEH dual inhibitor PTUPB ameliorates cecal ligation and puncture-induced sepsis in mice via anti-inflammation and anti-oxidative stress

Zhang, Yanfeng; Sun, Chaofen; Duan, Jia‐Xi; Yang, Huihui; Zhang, Chenyu; Xiong, Jian‐Bing; Zhong, Wenjing; Zu, Cheng; Guan, Xin‐Xin; Jiang, Huiling; Hammock, Bruce D.; Hwang, Sung Hee; Zhou, Yong; Guan, Cha‐Xiang

doi:10.1016/j.biopha.2020.109907

Cited by 45 publications

(27 citation statements)

References 57 publications

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“…Cancer progression is stimulated by inflammation, fibrosis, and oxidative stress. Dual COX-2/sEH inhibition via PTUPB inhibits allergic airway inflammation, pulmonary fibrosis, kidney injury and sepsis via anti-oxidative stress ( Dileepan et al, 2019 ; Hye Khan et al, 2016 ; Zhang et al, 2020 ; Zhang et al, 2019 ) . Dual COX-2/sEH inhibition inhibits primary tumor growth including glioblastoma growth, metastasis and potentiates the antitumor efficacy of chemotherapeutic agents such as cisplatin ( Li et al, 2017 ; Wang et al, 2018 ; Zhang, Panigrahy, et al, 2014 ).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

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138

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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

138

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“…It is well-known that oxidative stress plays important role in endothelial dysfunction, lung disease, gastrointestinal dysfunction, and atherosclerosis, and inflammatory symptoms are involved in all these disorders [ 112 , 113 ]. Excessive pro-inflammatory cytokines and mitochondrial dysfunction induce oxidative stress, characterized by an imbalance between the effectiveness of antioxidant defense and the speed of ROS generation, causing a net overload of oxidants [ 114 , 115 , 116 ].…”

Section: Anti-inflammatory Molecules Of Medicinal Plants and Mechamentioning

confidence: 99%

“…Besides, free arachidonic acid can be metabolized to various lipid mediators known as eicosanoids via the lipoxygenases and cyclooxygenase pathways [ 132 , 133 ]. Furthermore, arachidonic acid can be metabolized to prostaglandins and epoxyeicosatrienoic acids by cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP), respectively [ 114 , 134 , 135 ].…”

Section: Anti-inflammatory Molecules Of Medicinal Plants and Mechamentioning

confidence: 99%

“…Thus, arachidonic acid metabolites play a vital role in inflammation. In inflammatory conditions, arachidonic acid is released from membrane phospholipids by the enzyme phospholipase A2 and metabolized by cyclooxygenases, lipoxygenases, and cytochrome P450s (CYPs) to prostaglandins/thromboxane, leukotrienes, and epoxy/hydroxy-metabolites such as epoxyeicosatrienoic acids and other EpFAs, respectively [ 114 , 136 , 137 ]. Cyclooxygenase (COX), an enzyme responsible for the generation of prostaglandins (PG) from arachidonic acid, which is released from phospholipids of the cell membrane by phospholipase, has an induced form (COX-2) and a constitutive form (COX-1) [ 114 ].…”

Section: Anti-inflammatory Molecules Of Medicinal Plants and Mechamentioning

confidence: 99%

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Plants as Sources of Anti-Inflammatory Agents

et al. 2020

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Plants represent the main source of molecules for the development of new drugs, which intensifies the interest of transnational industries in searching for substances obtained from plant sources, especially since the vast majority of species have not yet been studied chemically or biologically, particularly concerning anti-inflammatory action. Anti-inflammatory drugs can interfere in the pathophysiological process of inflammation, to minimize tissue damage and provide greater comfort to the patient. Therefore, it is important to note that due to the existence of a large number of species available for research, the successful development of new naturally occurring anti-inflammatory drugs depends mainly on a multidisciplinary effort to find new molecules. Although many review articles have been published in this regard, the majority presented the subject from a limited regional perspective. Thus, the current article presents highlights from the published literature on plants as sources of anti-inflammatory agents.

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“…In addition, it has been reported that COX-2 has an effect on NLRP3 and NLRP3 inflammasome activation that is regulated by dephosphorylation of COX-2 modified by PP2A [46], and COX-2 mediateds the enhancement of lipopolysaccharide-induced pro-IL-1β and NLRP3 expression by increasing NF-kB activation and enhancing caspase-1 activation by increasing damaged mitochondria [47]; these effects are inhibited by the COX-2 inhibitor celecoxib. It has also been s reported that PTUPB, a dual COX-2 and sEH inhibitor, also inhibits the activation of NLRP3 inflammasomes [48,49]. We speculate that MCC950 might reduce inflammation by blocking the positive feedback of COX-2 on NLRP3 inflammasomes.…”

Section: Discussionmentioning

confidence: 56%

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

et al. 2020

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Background: Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear. Methods: To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, 30 female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E 2 (PGE 2) and prostaglandin F 2 alpha (PGF 2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis. Results: MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF 2α and PGE 2 , and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus. Conclusions: MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.

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A COX-2/sEH dual inhibitor PTUPB ameliorates cecal ligation and puncture-induced sepsis in mice via anti-inflammation and anti-oxidative stress

Cited by 45 publications

References 57 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Plants as Sources of Anti-Inflammatory Agents

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

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