Natural Products as a Novel Therapeutic Strategy for NLRP3 Inflammasome-Mediated Gout

Abstract

Gout is the most common form of inflammatory arthritis. It occurs when monosodium urate crystals (MSU) are deposited within joints due to hyperuricemia and persistent elevations of serum uric acid levels. Traditional gout treatment such as urate-lowering therapy is difficult to continue for a long period of time due to the risk of side effects. Recent studies have shown that the modulation of MSU-induced inflammatory responses is dependent on the inflammatory cytokine IL-1β, which has a central role in a chain of processes involving multiple cytokines and mediators. In this regard, the NLRP3 inflammasome is known to play a crucial part and thus has been proposed as a novel target in the treatment for gout. However, the biochemical mechanism for NLRP3 inflammasome activation has not yet been clearly elucidated. Therefore, this report can provide an overview of natural extractions targeted to prevent or treat NLRP3 inflammasome-mediated gout in the MSU-induced gout model. In addition, the research and development of such natural products are suggested as a potential strategy in the treatment of gout.

Molecular Foundations of Inflammatory Diseases: Insights into Inflammation and Inflammasomes

“…It is interesting to note that in response to MSU and FFA infusion, animals lacking caspase-1 and ASC significantly reduced their release of IL-1β. However, mice lacking the NLRP3 gene did not exhibit the same reduction [106,107].…”

The alleviatory effects of koumine on MSU‐induced gouty arthritis via the TLR4/NF‐κB/NLRP3 pathway

“…8 The deposition of MSU crystals in joints leads to an influx of neutrophils and increased secretion of proinflammatory cytokines by monocytes, further contributing to an inflammatory response. 9 Interleukin-1β (IL-1β) is a common proinflammatory cytokine that can participate in the progression of gout inflammation by causing vasodilation and rapid recruitment of neutrophils to sites of crystal deposition. 1,10 Nucleotide-binding oligomerization domain, leucinerich repeat and pyrin domain-containing 3 (NLRP-3) inflammasomes are the primary mechanisms for IL-1β maturation and secretion, and their abnormal activation leading to massive IL-1β release is thought to contribute to the pathogenesis of gout.…”

Potential roles of NLRP3 inflammasome in the pathogenesis of Kawasaki disease

“…A wide range of PAMPs and DAMPs that disrupt cellular hemostasis can be detected by NLRP3 (Liston & Masters, 2017). In recent years, copious shreds of evidence have shown the association between damaging inflammation related to NLRP3 and different diseases such as multiple sclerosis (Cui et al, 2022, Yi, 2021), Alzheimer's disease (Heneka et al, 2013; Merighi et al, 2022), psoriasis (Ciążyńska et al, 2021), gout (J. H. Lee et al, 2022; Zhong et al, 2022), and autoinflammatory conditions (Caseley et al, 2022; Nakanishi et al, 2022; Zhou et al, 2022). As mentioned earlier, there are several pieces of evidence that show the pivotal roles of NLRP3 inflammasome in the immunopathogenesis of KD.…”