ArticleInflammopharmacology2021
Novel complementary coloprotective effects of metformin and MCC950 by modulating HSP90/NLRP3 interaction and inducing autophagy in rats.
Article in Inflammopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.Drug design, development and therapy · 2024Trial
- Modulation of mTOR, NLRP3, and Nrf2/HO-1 signaling by atorvastatin and nitazoxanide in experimental ulcerative colitis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications.iScience · 2026Review
- Ulcerative colitis: signaling pathways, therapeutic targets and interventional strategies.Signal transduction and targeted therapy · 2026Review
- Therapeutic impacts of oral anti-diabetic drugs on Inflammatory Bowel Disease (IBD), a comprehensive review of clinical and preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Review on advances in small molecule inhibitors on the treatment of inflammatory bowel disease.Molecular biology reports · 2026Review
- The NLRP3 inhibitor, MCC950, attenuates environmental pollutant PMCurrent research in toxicology · 2026Article
- Mitophagy in inflammatory bowel disease: regulatory mechanisms and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Metformin Inhibits Inflammation by Targeting the NLRP3 Inflammasome: Linking NF-κB/NEK7/AMPK Signaling to Mitochondrial Function.Journal of inflammation research · 2026Review
- Targeting the NEK7/NLRP3 Inflammasome Axis: Synergistic Protection of Intravitreal MCC950 and Systemic Metformin Against Diabetic Retinopathy in Rats.Endocrinology, diabetes & metabolism · 2026Article
- Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach.World journal of gastroenterology · 2025Review
- NLRP3-Mediated PANoptosis and Associated Interventions in Endothelial Injury.Cardiovascular toxicology · 2025Review
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- Colo-Protective Effects of Pentoxifylline Alone or in Combination With Mesalamine in Colitis Through Sphingosine Kinase 1/Sphingosine 1 Phosphate, and Zonula Occuldin 1 Pathways: New Molecular Approach.Pharmacology research & perspectives · 2025Article
- Article
- NLRP3 inflammasomes pathway: a key target for Metformin.Inflammopharmacology · 2025Review
- Article
- GM-CSFTheranostics · 2025Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder, which has an increased incidence worldwide. The NLRP3 inflammasome has recently been assigned as a promising target for several inflammatory diseases including bowel inflammation. We aimed to investigate the potential complementary effects of combined therapy of metformin and MCC950 in dextran sodium sulfate (DSS)-induced colitis in rats. Metformin/MCC950 mitigated colon shortening, disease activity index (DAI), and macroscopic damage index (MDI). It also improved the colon histology picture and reduced the inflammation score. In addition, metformin/MCC950 augmented the antioxidant defense machinery and attenuated the myeloperoxidase (MPO) activity. Moreover, the levels of the pro-inflammatory mediators tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were reduced. This pharmacological activity might be attributed to interrupting the priming signal of the NLRP3 inflammasome activation through inactivating Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa-B (NF-κB) signalling (effect of metformin) as well as interrupting the activation signal through potent inhibition of NLRP3 expression and caspase-1 (effect of MCC950). As a result, significant inhibition of the production of the bioactive IL-1β and IL-18 occurred, and hence the pyroptosis process was inhibited. Moreover, the metformin/MCC950 leads to the induction of autophagy by AMP-activated protein kinase (AMPK)-dependent mechanisms leading to the accumulation of Beclin-1 and a substantial decline in the levels of p62 SQSTM1 (effect of metformin). The observed impeding effect on HSP90 along with inducing autophagy (effect of metformin) suggests that NLRP3 is prone to autophagic degradation. In conclusion, we reveal that the combination of metformin with MCC950 has a protective role in DSS-induced colitis and might become a candidate in a promising approach for the future treatment of human UC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.