Yasamin Hosseini, Amirhossein Niknejad, Ayeh Sabbagh Kashani, Mahsa Gholami, Mahtab Roustaie, Mohammad Mohammadi, Saeideh Momtaz, Stephen L Atkin, Tannaz Jamialahmadi, Amir Hossein Abdolghaffari, Amirhossein Sahebkar
{"title":"NLRP3 inflammasomes pathway: a key target for Metformin.","authors":"Yasamin Hosseini, Amirhossein Niknejad, Ayeh Sabbagh Kashani, Mahsa Gholami, Mahtab Roustaie, Mohammad Mohammadi, Saeideh Momtaz, Stephen L Atkin, Tannaz Jamialahmadi, Amir Hossein Abdolghaffari, Amirhossein Sahebkar","doi":"10.1007/s10787-025-01702-4","DOIUrl":null,"url":null,"abstract":"<p><p>Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing 3 (NLRP3) is a signaling pathway that is involved in inflammatory cascades, cell survival and the immune response. NLRP3 is activated by cellular damage, oxidative stress, and other factors that stimulate the immune system. Stimulation of NLRP3 induces inflammatory reactions and the production of inflammatory cytokines. These inflammatory mediators are implicated in several diseases. Metformin (MET) is an anti-hyperglycemia agent that is extensively used in clinical practice worldwide due to its high efficiency, safety profile, and affordable price. MET is the only member of biguanide class that is used in clinical practice and a potent AMP-activated protein kinase (AMPK) agonist with proven anti-inflammatory characteristics. Due to its anti-inflammatory properties, MET is considered to be effective against diseases that have an inflammatory background, and the NLRP3 pathway is involved in the pathophysiology of these disorders. In this review, we have evaluated the evidence if MET can affect this pathway and its utility for future therapeutic approaches.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-025-01702-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing 3 (NLRP3) is a signaling pathway that is involved in inflammatory cascades, cell survival and the immune response. NLRP3 is activated by cellular damage, oxidative stress, and other factors that stimulate the immune system. Stimulation of NLRP3 induces inflammatory reactions and the production of inflammatory cytokines. These inflammatory mediators are implicated in several diseases. Metformin (MET) is an anti-hyperglycemia agent that is extensively used in clinical practice worldwide due to its high efficiency, safety profile, and affordable price. MET is the only member of biguanide class that is used in clinical practice and a potent AMP-activated protein kinase (AMPK) agonist with proven anti-inflammatory characteristics. Due to its anti-inflammatory properties, MET is considered to be effective against diseases that have an inflammatory background, and the NLRP3 pathway is involved in the pathophysiology of these disorders. In this review, we have evaluated the evidence if MET can affect this pathway and its utility for future therapeutic approaches.
期刊介绍:
Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas:
-Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states
-Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs
-Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents
-Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain
-Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs
-Muscle-immune interactions during inflammation [...]