Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

Wu, Jiasi; Luo, Yong; Jiang, Qing; Li, Sheng; Huang, Weicai; Li, Xiang; Liu, De-ming; Hu, Yingfan; Wang, Ping; Lu, Xiaoxia; Zhang, Guolin; Wang, Fei; Meng, Xianli

doi:10.1016/j.phrs.2019.104348

Cited by 63 publications

(53 citation statements)

References 41 publications

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“…Accordingly, natural products which exert properties to block inflammatory signalling transduction by inactivating targets macrophages. 53 Similarly, inhibition of inflammatory process was also observed in animal models including xylene-induced ear oedema, carrageenan-elicited paw oedema, LPS-induced shock, OVA-induced allergic rhinitis and MSU-elicited gouty after coptisine administration. 54 Mechanistically, coptisine (50-200 mg/kg, oral, once daily for 10 days; 10-40 mg/kg, oral, once daily for 7 days; 2.91-11.61 mg/ F I G U R E 4 Schematic summaries of coptisine's anti-inflammatory and CVD protection targets.…”

Section: Anti -C An Cer Propert Ymentioning

confidence: 86%

“…In the work of Ren et al, CC ameliorated renal damage of rats with early obesity‐related glomerulopathy by interfering the activation of NLRP3 inflammasome, and this effect was confirmed to be related to coptisine, the main constituent of CC . Coptisine (1‐30 μmol/L, 3.75 hours) was reported to inhibit caspase‐1 cleavage in LPS plus ATP/MSU/Nigericin through preventing NLRP3 inflammasome priming and assembling in stimulated Raw 264.7 macrophages …”

Section: Anti‐inflammation Propertymentioning

confidence: 91%

“…Similarly, inhibition of inflammatory process was also observed in animal models including xylene‐induced ear oedema, carrageenan‐elicited paw oedema, LPS‐induced shock, OVA‐induced allergic rhinitis and MSU‐elicited gouty after coptisine administration . Mechanistically, coptisine (50‐200 mg/kg, oral, once daily for 10 days; 10‐40 mg/kg, oral, once daily for 7 days; 2.91‐11.61 mg/kg, i.v, single dose, 0‐24 hours) diminished cytokine production through blocking inflammatory transduction mediated by the phosphorylation of IKKα/β and MAPK subfamilies, the translocation and degradation of p65 in oedema tissue as well as suppression of NLRP3 inflammasome activation . Of interest, coptisine (0.97‐3.87 mg/kg, i.v; single dose, 0‐4 hours) showed no effect on the up‐regulation of oedema skin temperature induced by carrageenan subcutaneously injection in rats .…”

Section: Anti‐inflammation Propertymentioning

confidence: 99%

“…Red arrows represent for decreased expression and/or activity; blue arrows represent for increased expression and/or activity kg, i.v, single dose, 0-24 hours) diminished cytokine production through blocking inflammatory transduction mediated by the phosphorylation of IKKα/β and MAPK subfamilies, the translocation and degradation of p65 in oedema tissue as well as suppression of NLRP3 inflammasome activation. 50,53,55 Of interest, coptisine (0.97-3.87 mg/kg, i.v; single dose, 0-4 hours) showed no effect on the up-regulation of oedema skin temperature induced by carrageenan subcutaneously injection in rats. 49 Furthermore, there is a study investigating a pharmacokinetic-pharmacodynamic model for coptisine challenge of inflammation in LPS-elicited rats, and authors emphasized early stage of TNF-α response is the key factor of the subsequent inflammatory cascade.…”

Section: Anti -C An Cer Propert Ymentioning

confidence: 99%

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Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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Section: Anti -C An Cer Propert Ymentioning

confidence: 86%

Section: Anti‐inflammation Propertymentioning

confidence: 91%

Section: Anti‐inflammation Propertymentioning

confidence: 99%

Section: Anti -C An Cer Propert Ymentioning

confidence: 99%

See 2 more Smart Citations

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

Self Cite

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“…Napagoda and colleagues showed that lipophilic extracts of Leucas zeylanica inhibited 5-LO, microsomal prostaglandin E2 synthase-1, and xanthine oxidase, rationalizing its application as anti-inflammatory and antigout remedy [ 15 ]. It appears that the reported underlying mechanisms for other TCM-based antigout therapies are mainly related to the inhibition of the NLRP3 pathway [ 13 , 43 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators

Deng

Chen

et al. 2020

Mediators of Inflammation

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The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an antigout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously downregulated. In conclusion, our study suggests that the antigout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.

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Inhibitory Effects of Corydalis saxicola Bunting Total Alkaloids on Macrophage Pyroptosis

Feng

Yong

Jiang

et al. 2023

Chemistry & Biodiversity

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This study investigated the effect of Corydalis saxicola Bunting total alkaloids (CSBTA) on pyroptosis in macrophages (Mϕ). In the Mϕ pyroptosis model, an inverted fluorescence microscope was used to assess cell pyroptosis, while a scanning electron microscope was used to observe morphological changes in Mϕ. NLR family pyrin domain‐containing 3 (NLRP3), caspase‐1, and gasdermin D (GSDMD) expression levels were detected by polymerase chain reaction and western blotting, whereas interleukin‐1 (IL‐1) and interleukin‐18 (IL‐18) expression levels were measured by an enzyme‐linked immunosorbent assay. After pretreatment with CSBTA or the caspase‐1 inhibitor, acetyl‐tyrosyl‐valyl‐alanyl‐aspartyl‐chloromethylketone (Ac‐YVAD‐cmk), it was discovered that NLRP3, caspase‐1, and GSDMD expressions were significantly reduced at both the mRNA and protein levels, as were IL‐1 and IL‐18 levels. The inhibitory effects of CSBTA and Ac‐YVAD‐cmk did not differ significantly. These findings indicate that CSBTA blocks Porphyromonas gingivalis‐lipopolysaccharide‐induced Mϕ pyroptosis.

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Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

Cited by 63 publications

References 41 publications

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators

Inhibitory Effects of Corydalis saxicola Bunting Total Alkaloids on Macrophage Pyroptosis

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