Curcumin suppresses NLRP3 inflammasome activation and protects against LPS‐induced septic shock

Gong, Zizhen; Zhou, Jun; Li, Hui; Gao, Yanhong; Xu, Congfeng; Zhao, Shengnan; Chen, Yingwei; Cai, Wei; Wu, Jin Shang

doi:10.1002/mnfr.201500316

Cited by 113 publications

(72 citation statements)

References 45 publications

(57 reference statements)

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“…Consistent with recent studies, curcumin prevented the decline of intracellular K + in response to incubation with the NLRP3 activators nigericin and MSU ( Fig. 4A) (18). Results were confirmed by ICP-OES ( Fig.…”

Section: Curcumin Inhibits Potassium Effluxsupporting

confidence: 91%

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome

Yin

Guo

et al. 2018

The Journal of Immunology

169

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Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1β secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes. Curcumin inhibited the NLRP3 inflammasome by preventing K efflux and disturbing the downstream events, including the efficient spatial arrangement of mitochondria, ASC oligomerization, and speckle formation. Reactive oxygen species, autophagy, sirtuin-2, or acetylated α-tubulin was ruled out as the mechanism by which curcumin inhibits the inflammasome. Importantly, in vivo data show that curcumin attenuated IL-1β secretion and prevented high-fat diet-induced insulin resistance in wide-type C57BL/6 mice but not in -deficient mice. Curcumin also repressed monosodium urate crystal-induced peritoneal inflammation in vivo. Taken together, we identified curcumin as a common NLRP3 inflammasome activation inhibitor. Our findings reveal a mechanism through which curcumin represses inflammation and suggest the potential clinical use of curcumin in NLRP3-driven diseases.

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Section: Curcumin Inhibits Potassium Effluxsupporting

confidence: 91%

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome

Yin

Guo

et al. 2018

The Journal of Immunology

169

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“…Gong et al () have studied the effect of curcumin on treated murine macrophage cell line J774A with septic shock and reported that curcumin inhibited the Nod‐like receptor pyrin domain‐containing protein 3 inflammasome activators significantly, consequently decreased the level of activated caspase‐1, which leads to a decrease in IL‐1 β secretion as well as improves the condition of illness caused by endotoxic shock.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammasome such as Nod-like receptor pyrin domain-containing protein 3 (NLRP3) is a cytoplasmic multiportion complex of the innate immune system (Hao et al, 2017) that leads to maturation and production of cytokines such as IL-18, IL-1β, and pyroptosis (lytic host cell death; Liu, Jing, et al, 2018;Luo et al, 2014). Gong et al (2015) have studied the effect of curcumin on treated murine macrophage cell line J774A with septic shock and reported that curcumin inhibited the Nod-like receptor pyrin domain-containing protein 3 inflammasome activators significantly, consequently decreased the level of activated caspase-1, which leads to a decrease in IL-1 β secretion as well as improves the condition of illness caused by endotoxic shock.…”

Section: Inhibition Of Nod-like Receptor Pyrin Domaincontaining Promentioning

confidence: 99%

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Karimi

Ghodsi

Kooshki

et al. 2019

Phytotherapy Research

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Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti‐inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English‐language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis‐induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.

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“…Macrophages, along with other immune cells, such as neutrophils, play a vital role in mediating joint inflammation in gout. 17,[21][22][23] Stimulating with MSU, the macrophages can release IL-1β, a cytokine crucial to initiate out pathogenesis and neutrophil recruitment. 24 Mature and functional IL-1β is The protein expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β were evaluated in the whole cell lysates.…”

Section: Discussionmentioning

confidence: 99%

“…17,[21][22][23] Stimulating with MSU, the macrophages can release IL-1β, a cytokine crucial to initiate out pathogenesis and neutrophil recruitment. 17,[21][22][23] Stimulating with MSU, the macrophages can release IL-1β, a cytokine crucial to initiate out pathogenesis and neutrophil recruitment.…”

Section: Msu-induced Gouty Arthritis Modelmentioning

confidence: 99%

Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling

Sun

et al. 2018

J of Cellular Biochemistry

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Background Monosodium urate (MSU) crystals‐induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti‐inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive. Methods We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals–stimulated cells were collected and subjected to enzyme‐linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod‐like receptor 3 (NLRP3) inflammasome/nuclear factor‐kappa B (NF‐κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU‐induced gouty arthritis rat models. Results Curcumin could reduce MSU crystals‐induced IL‐1β and TNF‐α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase‐1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU‐induced NF‐κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU‐induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL‐1β, TNF‐α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase‐1, caspase‐1, pro‐IL‐1β, and IL‐1β were downregulated by curcumin in vivo. Conclusions These results indicated that curcumin could effectively ameliorate MSU crystal‐induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF‐κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

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Curcumin suppresses NLRP3 inflammasome activation and protects against LPS‐induced septic shock

Abstract: Curcumin potently inhibits the activation of NLRP3 inflammasome which may contribute to its anti-inflammatory activity. Our finding offers a mechanistic basis for the therapeutic potential of curcumin in septic shock and other NLRP3 inflammasome-driven diseases.

Cited by 113 publications

References 45 publications

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies

Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling

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