NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice

Xue, Ying; Ran, Li; Fang, Ping; Ye, Zheng-qin; Zhao, Yong; Zhou, Yun; Zhang, Ke‐Qin; Li, Ling

doi:10.1530/jme-20-0305

Cited by 24 publications

(16 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of cell experiments were highly consistent with the results of the animal experiments, further suggesting that the active flavonoids can attenuate gouty arthritis by regulating the TLR4/MyD88/NF-κB pathway and NLRP3 levels. NLRP3 inflammasome inhibitor was also shown to suppress gouty arthritis in mice (Xue et al, 2021). However, another recent study showed that NLRP3 inhibitor did not significantly suppress MSU crystal-induced necrosis in macrophages (Zhong et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Active Flavonoids From Lagotis brachystachya Attenuate Monosodium Urate-Induced Gouty Arthritis via Inhibiting TLR4/MyD88/NF-κB Pathway and NLRP3 Expression

Ouyang

Guo

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Lagotis brachystachya Maxim is a characteristic herb commonly used in Tibetan medicine. Tibetan medicine records it as an important medicine for the clinical treatment of “Yellow Water Disease,” the symptoms of which are similar to that of arthritis. Our previous study showed that the flavonoid fraction extracted from L. brachystachya could attenuate hyperuricemia. However, the effects of the active flavonoids on gouty arthritis remain elusive, and the underlying mechanism is not understood. In the present study, the effects of the active flavonoids were evaluated in rats or Raw264.7 cells with gouty arthritis induced by monosodium urate (MSU) crystal, followed by the detection of TLR4, MyD88, pNF-κB, and NLR family pyrin domain-containing 3 (NLRP3) expression. The swelling of the ankle joint induced by MSU crystal began to be relieved 6 h post the administration with the active flavonoids. In addition, the active flavonoids not only alleviated MSU crystal-induced inflammation in synovial tissues by histopathological examination but also reduced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the joint tissue fluid of MSU crystal-induced rats. Furthermore, Western blot analysis indicated that the active flavonoids reduced the production of these cytokines by inhibiting the TLR4/MyD88/NF-κB pathway and decreasing NLRP3 expression in synovial tissues of rats. More importantly, the inhibition of TLR4/MyD88/NF-κB pathway and NLRP3 expression was also confirmed in MSU-induced Raw264.7 cells. In conclusion, these results indicated that the active flavonoids from L. brachystachya could effectively attenuate gouty arthritis induced by MSU crystal through the TLR4/MyD88/NF-κB pathway and NLRP3 expression in vivo and in vitro, suggesting several potential candidates for the treatment of gouty arthritis.

show abstract

Section: Discussionmentioning

confidence: 99%

Active Flavonoids From Lagotis brachystachya Attenuate Monosodium Urate-Induced Gouty Arthritis via Inhibiting TLR4/MyD88/NF-κB Pathway and NLRP3 Expression

Ouyang

Guo

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Xue et al confirmed that CUB could significantly reduce IL-1β secretion by blocking the formation of NLRP3 inflammasome and inhibiting the key enzymes of macrophage glycolysis. Through histopathological analysis, the authors also showed that CUB improved foot swelling and inflammatory cell infiltration in gouty arthritis mice [112].…”

Section: Terpenoidsmentioning

confidence: 93%

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

2023

Curr Res Cmpl Alt Med

View full text Add to dashboard Cite

Gout is an inherited metabolic disorder resulting from abnormalities in purine metabolism manifesting as episodes of acute inflammatory arthritis. The incidence of gout shows an increasing tendency each year, due to the complicated pathogenesis, the currently available drugs have poor treatment effects on it. Therefore, the development of effective drugs for gout treatment is urgently needed. Because of its high biological activity and safety, Traditional Chinese medicine (TCM) has significant advantages in the prevention and treatment of gout. This paper systematically reviewed the related research on TCM's treatment of gout in the previous five years, and summarized the actions and mechanisms of 25 Chinese herbal extracts, 38 Chinese medicinal monomers, and 19 Chinese medicinal compounds in the treatment of gout, including serum uric acid levels reduction, anti-inflammation, and anti-oxidative stress. These primarily involve the signaling pathways NLRP3/ASC/caspase, TLRs/MYD88/NF-κB, ATP/ P2X7R, and others. Furthermore, the limitations and shortcomings of the experimental study on the treatment of gout with TCM are discussed and appropriate measures are proposed. To summarize, TCM is likely to be a potential candidate for gout treatment, but more clinical research is needed to fully understand its role in the treatment of gout.

show abstract

“…Emerging evidence suggested that CuB effectively decreased IL-1b secretion and the production of key enzymes of glycolysis in macrophages. In vivo studies have shown that CuB pretreatment also ameliorated foot and ankle swelling and inflammatory cell infiltration, which may be developed as a promising anti-GA agents (64). Wu et al reported that Coptisine from Coptis chinensis directly inhibited caspase-1, and further blocked NLRP3 inflammasome activation.…”

Section: Nlrp3 Polymorphisms With Susceptibility To Gamentioning

confidence: 99%

Role of NLRP3 in the pathogenesis and treatment of gout arthritis

Liu

Wang

2023

Front. Immunol.

View full text Add to dashboard Cite

Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.

show abstract

NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice

Cited by 24 publications

References 70 publications

Active Flavonoids From Lagotis brachystachya Attenuate Monosodium Urate-Induced Gouty Arthritis via Inhibiting TLR4/MyD88/NF-κB Pathway and NLRP3 Expression

Active Flavonoids From Lagotis brachystachya Attenuate Monosodium Urate-Induced Gouty Arthritis via Inhibiting TLR4/MyD88/NF-κB Pathway and NLRP3 Expression

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

Role of NLRP3 in the pathogenesis and treatment of gout arthritis

Contact Info

Product

Resources

About