The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 10, 2022

The NLRP3 inflammasome is a multiprotein complex that plays pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs DAMPs, oligomerizes activates caspase-1 which initiates processing release of pro-inflammatory cytokines IL-1β IL-18. most extensively studied to date due its array activators aberrant several diseases. Studies using small molecules biologics targeting pathway have shown positive outcomes treating various disease pathologies blocking chronic inflammation. In this review, we discuss recent advances understanding mechanism, pathology, provide broad review therapeutics discovered target their challenges.

Language: Английский

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Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside

Nutrients, Journal Year: 2022, Volume and Issue: 14(6), P. 1155 - 1155

Published: March 9, 2022

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, other organoleptic characteristics, as well contributing to important nutritional aspects. Beyond these due their biochemical properties they considered bioactive compounds. Several studies have demonstrated biological activity different cellular physiological processes high-order organisms including humans. The flavonoid molecular structure confers capability of reacting with neutralizing reactive oxygen species (ROS), behaving scavengers all generating this class molecules, such UV irradiation, a process widely present plant physiology. Importantly, recent scientific literature has that flavonoids, human physiology, active compounds acting not only but also role counteracting inflammation process. Among wide variety significant results been shown investigating flavones luteolin luteolin-7-O-glucoside (LUT-7G). For compounds, experimental an anti-inflammatory action, both vitro vivo, interaction JAK/STAT3, NF-κB, pathways described review. We describe effects metabolic connected inflammation, glycolysis, diabetes, lipid peroxidation, cancer cells. Moreover, inhibition inflammatory pathway endothelial tissue, NLRP3 inflammasome assembly, demonstrates key progression phenomena. Since micronutrient obtained from food, open new perspectives respect long-term health status healthy individuals, use coadjutant treatment specific diseases.

Language: Английский

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The Interaction between Flavonoids and Intestinal Microbes: A Review

Foods, Journal Year: 2023, Volume and Issue: 12(2), P. 320 - 320

Published: Jan. 9, 2023

In recent years, research on the interaction between flavonoids and intestinal microbes have prompted a rash of food science, nutriology biomedicine, complying with future trends. The gut microbiota plays an essential role in maintenance homeostasis human health, but once flora dysregulation occurs, it may contribute to various diseases. Flavonoids shown variety physiological activities, are metabolized or biotransformed by microbiota, thereby producing new metabolites that promote health modulating composition structure flora. Herein, this review demonstrates key notion as well dysbiosis, aiming provide comprehensive understanding about how regulate diseases microbiota. Emphasis is placed microbiota-flavonoid bidirectional affects metabolic fate their metabolites, influencing mechanism, biotransformation, bioavailability bioactivity. Potentially focusing abundance diversity such bile acids, we discuss influence mechanism protecting barrier function immune system. Additionally, crucial regulating We explain underlying regulation several typical including gastrointestinal diseases, obesity, diabetes cancer, theoretical basis guideline for promotion treatment

Language: Английский

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ROS-responsive nanoparticles for oral delivery of luteolin and targeted therapy of ulcerative colitis by regulating pathological microenvironment

Materials Today Bio, Journal Year: 2022, Volume and Issue: 14, P. 100246 - 100246

Published: March 1, 2022

Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated d-α-tocopherol polyethylene glycol succinate-b-poly(β-thioester) copolymer (TPGS-PBTE) for ROS cleavage via colitis-targeted delivery luteolin (LUT), natural flavonoid good anti-inflammation radical-scavenging activity. Owing to thioether bond polymer main chain, TPGS-PBTE exhibited size change drug release, which benefited ROS-scavenging selective accumulation LUT inflamed colon. In dextran sulfate sodium-induced acute murine model, LUT@TPGS-PBTE alleviated body weight loss, colon length shortening, damage colonic tissues due suppression proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), well upregulation glutathione anti-inflammatory factors IL-10, IL-4). More importantly, regulated inflammatory microenvironment modulating T helper (Th)1/Th2 Th17/regulatory cell (Treg) balance (i.e., increased numbers Tregs Th2 cells decreased Th1 Th17 ​cells), thus resolving inflammation accelerating healing intestinal mucosa. Additionally, formulation enabled reduction effective dose showed excellent biosafety mouse demonstrating its potential targeted therapeutic preparation.

Language: Английский

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Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review

Phytomedicine, Journal Year: 2023, Volume and Issue: 119, P. 154979 - 154979

Published: July 18, 2023

Language: Английский

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Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence

Phytomedicine, Journal Year: 2023, Volume and Issue: 111, P. 154658 - 154658

Published: Jan. 12, 2023

Wumei Wan (WMW) has been used to address digestive disorder for centuries in traditional Chinese medicine. Previous studies have demonstrated its anti-colitis efficacy, but the underlying mechanism of action remains be further clarified.To investigate mechanisms WMW treatment chronic ulcerative colitis (UC) through network pharmacology and experimental validation.Traditional Medicine Systems Pharmacology (TCMSP) platform were identify ingredients potential targets WMW. The microarray gene data GSE75214 datasets from GEO database was define UC-associated targets. Cytoscape3.7.2 employed construct protein-protein interaction (PPI) compounds-disease network. GO enrichment analysis KEGG pathway performed by R software functional annotation. UPLC-TOF-MS/MS method quantitatively analyze active For validation, three cycles 2% dextran sulfate sodium salt (DSS) model. hub signal detected qPCR, ELISA, western blotting , immunohistochemical immunofluorescence.Through analysis, 104 obtained WMW, 47 these had UC. A total 41 13 identified. showed that involved advanced glycation end products-receptor products (AGE-RAGE) signaling pathway. Taxifolin, rutaecarpine, kaempferol, quercetin, luteolin more highly predictive components related AGE-RAGE In vivo improved DSS-induced colitis, reduced expression inflammatory cytokines chemokines. Notably, it significantly decreased mRNA Spp1, Serpine1, Mmp2, Mmp9, Ptgs2, Nos2, Kdr Icam1, which associated with angiogenesis. addition, we confirmed inhibited RAGE diminished epithelial barrier alterations CONCLUSION: Our results initially effective strong anti-angiogenic activity colitis. Sufficient evidence satisfactory verified this study, suggesting as a quite prospective agent therapy

Language: Английский

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The role of gut microbiota in intestinal disease: from an oxidative stress perspective

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 14, 2024

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn’s disease. The level of reactive oxygen species (ROS) has been reported to increase when the microbiota dysregulated, especially several bacterial metabolites are present. Although healthy plays a vital role in defending against excessive stress, disease influenced by ROS, this process controlled immunological responses, DNA damage, inflammation. In review, we discuss relationship between from an perspective. addition, also provide summary most recent therapeutic approaches for preventing or treating modifying microbiota.

Language: Английский

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Luteolin: A promising multifunctional natural flavonoid for human diseases

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(7), P. 3417 - 3443

Published: April 26, 2024

Abstract Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It noteworthy that LUT exhibits variety of beneficial pharmacological properties holds significant potential for clinical applications, particularly antitumor, anti‐convulsion, diabetes control, anti‐inflammatory, neuroprotection, anti‐oxidation, anti‐cardiovascular, other aspects. The mechanism action has been partially elucidated, including the mediation NF‐κB, toll‐like receptor, MAPK, Wnt/β‐catenin, PI3K/Akt, AMPK/mTOR, Nrf‐2, among others. review aimed to comprehensively consolidate essential information on natural sources, effects, therapeutic preventive potential, as well mechanisms LUT. objective establish theoretical basis continued development application

Language: Английский

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Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 328, P. 117956 - 117956

Published: Feb. 29, 2024

Language: Английский

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The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

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