Celastrol ameliorates murine colitis via modulating oxidative stress, inflammatory cytokines and intestinal homeostasis

Shaker, Mohamed E.; Ashamallah, Sylvia A.; Houssen, Maha E.

doi:10.1016/j.cbi.2013.12.007

Cited by 82 publications

(49 citation statements)

References 46 publications

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“…Unlike neutrophils, macrophages infiltration identified by CD68 staining was not significantly reduced after celastrol treatment. These results suggested that celastrol could inhibit macrophages activation rather than migration [9].…”

Section: Discussionmentioning

confidence: 97%

“…The in vivo anti-inflammatory effects of this triterpene have been demonstrated in multiple animal models, including Alzheimer disease, asthma, systemic lupus erythematosus, and rheumatoid arthritis. Moreover, previous studies have revealed that celastrol can ameliorate mouse colitis and human Crohn's disease by inhibiting pro-inflammatory cytokine secretion [8][9].…”

Section: Introductionmentioning

confidence: 98%

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The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice

Jia

Shen

et al. 2015

International Immunopharmacology

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice

Jia

Shen

et al. 2015

International Immunopharmacology

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“…It is a kind of triterpenoid extracted from the root of a traditional Chinese medicine called Tripterygium wilfordii . It was reported that celastrol could inhibit the development of IBD or colitis through several pathways, including: (1) regulating the oxidative stress and reducing lipid peroxide; (2) inhibiting the activation of the NLRP3 inflammasome; (3) increasing the levels of anti-inflammatory cytokines like IL-10; (4) enhancing the stability of intestinal epithelial barrier (152); (5) inhibiting the receptor interacting-protein 3/mixed lineage kinase domain-like protein-mediated programed necrosis pathway (153); and (6) inhibiting the production of NF-κB and its related inflammatory cytokines (154). Furthermore, it has been proven that celastrol can enhance the level of autophagy through the inhibition of the PI3K/Akt/mTOR signaling pathway in the colon tissue, and meanwhile reduce the production of several pro-inflammatory cytokines thus attenuating the inflammatory reaction in colon in IL-10-deficient mice (155).…”

Section: Pharmacological Intervention Of Autophagy In the Treatment Omentioning

confidence: 99%

Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

Peng

Shao

et al. 2017

Front. Immunol.

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Intestinal mucosal barrier, mainly composed of the intestinal mucus layer and the epithelium, plays a critical role in nutrient absorption as well as protection from pathogenic microorganisms. It is widely acknowledged that the damage of intestinal mucosal barrier or the disturbance of microorganism balance in the intestinal tract contributes greatly to the pathogenesis and progression of inflammatory bowel disease (IBD), which mainly includes Crohn’s disease and ulcerative colitis. Autophagy is an evolutionarily conserved catabolic process that involves degradation of protein aggregates and damaged organelles for recycling. The roles of autophagy in the pathogenesis and progression of IBD have been increasingly studied. This present review mainly describes the roles of autophagy of Paneth cells, macrophages, and goblet cells in IBD, and finally, several potential therapeutic strategies for IBD taking advantage of autophagy.

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“…The doses of apocynin (100 mg/kg), naloxone (50 mg/kg), and celastrol (100 mg/kg) used here were selected on the basis of doses reported to be efficacious in various disease models (13,17,35,40,55). None of these three compounds showed NOX2 inhibition in the paw inflammation model.…”

mentioning

confidence: 99%

Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor

Hirano¹,

Chen²,

Chueng³

et al. 2015

Antioxidants & Redox Signaling

155

141

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Aims: The NADPH oxidase (NOX) family of enzymes catalyzes the formation of reactive oxygen species (ROS). NOX enzymes not only have a key role in a variety of physiological processes but also contribute to oxidative stress in certain disease states. To date, while numerous small molecule inhibitors have been reported (in particular for NOX2), none have demonstrated inhibitory activity in vivo. As such, there is a need for the identification of improved NOX inhibitors to enable further evaluation of the biological functions of NOX enzymes in vivo as well as the therapeutic potential of NOX inhibition. In this study, both the in vitro and in vivo pharmacological profiles of GSK2795039, a novel NOX2 inhibitor, were characterized in comparison with other published NOX inhibitors. Results: GSK2795039 inhibited both the formation of ROS and the utilization of the enzyme substrates, NADPH and oxygen, in a variety of semirecombinant cell-free and cellbased NOX2 assays. It inhibited NOX2 in an NADPH competitive manner and was selective over other NOX isoforms, xanthine oxidase, and endothelial nitric oxide synthase enzymes. Following systemic administration in mice, GSK2795039 abolished the production of ROS by activated NOX2 enzyme in a paw inflammation model. Furthermore, GSK2795039 showed activity in a murine model of acute pancreatitis, reducing the levels of serum amylase triggered by systemic injection of cerulein. Innovation and Conclusions: GSK2795039 is a novel NOX2 inhibitor that is the first small molecule to demonstrate inhibition of the NOX2 enzyme in vivo. Antioxid. Redox Signal. 23, 358-374.

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Celastrol ameliorates murine colitis via modulating oxidative stress, inflammatory cytokines and intestinal homeostasis

Cited by 82 publications

References 46 publications

The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice

The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice

Intestinal Autophagy and Its Pharmacological Control in Inflammatory Bowel Disease

Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor

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