Therapeutic interventions target the NLRP3 inflammasome in ulcerative colitis: Comprehensive study

Ali, Fares E.M.; Ibrahim, Islam; Ghogar, Osama M; Abd-alhameed, Esraa K.; Althagafy, Hanan S.; Hassanein, Emad H.M.

doi:10.3748/wjg.v29.i6.1026

Cited by 9 publications

(7 citation statements)

References 346 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies also find that compared to wild-type mice, mice with NLRP3 inflammasome deficiency exhibit exacerbated DSS-induced colitis and decreased epithelial integrity ( 32 ). Synthetic drugs, phytochemicals, and plant extracts exert colon-protective effects and inhibit NLRP3 and caspase-1 activation, demonstrating their role in UC inflammation ( 33 ). However, further understanding is needed on how inhibiting NLRP3 inflammasome activation can significantly treat IBD.…”

Section: The Classification Of Inflammasomesmentioning

confidence: 99%

Pyroptosis: a new insight into intestinal inflammation and cancer

Chao,

Zhang,

Feng

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Pyroptosis is an innate immune response triggered by the activation of inflammasomes by various influencing factors, characterized by cell destruction. It impacts the immune system and cancer immunotherapy. In recent years, the roles of pyroptosis and inflammasomes in intestinal inflammation and cancer have been continuously confirmed. This article reviews the latest progress in pyroptosis mechanisms, new discoveries of inflammasomes, mutual regulation between inflammasomes, and their applications in intestinal diseases. Additionally, potential synergistic treatment mechanisms of intestinal diseases with pyroptosis are summarized, and challenges and future directions are discussed, providing new ideas for pyroptosis therapy.

show abstract

Section: The Classification Of Inflammasomesmentioning

confidence: 99%

Pyroptosis: a new insight into intestinal inflammation and cancer

Chao,

Zhang,

Feng

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…5 Moreover, innate immune signaling mediated macrophages activation act as a primary response to promote the transcription of NOD-like receptor family pyrin domain containing 3 (NLRP3) through nuclear factor-κB (NF-κB) activation. 6 The NLRP3 inflammasome is a cytosolic protein complex, composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and pro-Caspase1. This complex is present in various immune cells and is crucial for maintaining gut homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…In response to pathogen‐associated molecular patterns (PAMPs), Toll‐like receptor (TLR) is activated, which in turn activates macrophages leading to excessive inflammation and tissue damage, causing colitis 5 . Moreover, innate immune signaling mediated macrophages activation act as a primary response to promote the transcription of NOD‐like receptor family pyrin domain containing 3 (NLRP3) through nuclear factor‐κB (NF‐κB) activation 6 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF‐κB pathway

Tong,

Chen,

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

BackgroundUlcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti‐inflammatory, antiobesity, and other biological activities. However, the therapeutic role and molecular mechanisms of PHI on UC are still insufficiently researched.MethodsIn this study, dextran sulfate sodium (DSS) and 2.5% 2,4,6‐trinitro‐Benzenesulfonic acid (TNBS)‐induced acute UC were used to investigate the therapeutic effects of PHI. We evaluated the effects of PHI on disease activity index (DAI), body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, enzyme‐linked immunosorbent assay (ELISA), RT‐qPCR, and Western blot analysis.ResultsOur findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce DAI and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Mechanistically, PHI may exert anti‐inflammatory effects by downregulating the TLR4/MyD88/NF‐κB pathway and inhibiting the activation of NLRP3 inflammasome.ConclusionIn conclusion, PHI possesses significant anti‐inflammatory properties and is expected to be a potential drug for UC treatment. Our study delves into the underlying mechanisms of PHI therapy and highlights the potential for further research in developing PHI‐based treatments for UC.

show abstract

“…Toll-like receptors (TLRs) are activated by pathogen-associated molecular patterns (PAMPs), which in turn activate macrophages leading to excessive inflammation and tissue damage, causing colitis [5]. Moreover, innate immune signaling via cytokine receptors and TLRs mediated macrophages activation act as a primary response to promote NOD-like receptor family pyrin domain containing 3 (NLRP3) transcription through NF-kB activation [6].…”

mentioning

confidence: 99%

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF-κB pathway

Tong,

Chen,

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Ulcerative colitis (UC) is a chronic inflammatory disease caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, known for its various bioactivities, including anti-inflammatory, anti-obesity, and antipyretic activities. However, the potential anti-inflammatory effects of PHI on UC and its underlying mechanisms are still poorly understood. Methods: In this study, we investigated the therapeutic effects of PHI on acute UC induced by DSS and TNBS. We evaluated the effects of PHI on disease activity index, body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, ELISA, RT-qPCR, and Western blotting. Results: Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce disease activity index and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Additionally, both in vivo and in vitro results suggested that PHI may exert anti-inflammatory effects by downregulating the TLR4/MyD88/NF-κB pathway, inhibiting NLRP3 inflammasome activation. Conclusion: In conclusion, PHI possesses anti-inflammatory properties and has the potential as a therapeutic agent for the treatment of UC. Our study provides insights into the underlying mechanisms of PHI’s therapeutic effects and highlights the potential for further research in developing PHI-based treatments for UC.

show abstract

Therapeutic interventions target the NLRP3 inflammasome in ulcerative colitis: Comprehensive study

Cited by 9 publications

References 346 publications

Pyroptosis: a new insight into intestinal inflammation and cancer

Pyroptosis: a new insight into intestinal inflammation and cancer

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF‐κB pathway

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF-κB pathway

Contact Info

Product

Resources

About