Celastrol inhibits rheumatoid arthritis through the ROS-NF-κB-NLRP3 inflammasome axis

Jing, Ming; Yang, Junjie; Zhang, Lirong; Jing, Liu; Xu, Sen; Wang, Meiling; Zhang, Leiming; Sun, Yue; Yan, Wei-Bin; Hou, Gui‐Ge; Wang, Chunhua; Xin, Wenyu

doi:10.1016/j.intimp.2021.107879

Cited by 62 publications

(36 citation statements)

References 43 publications

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“…As previously mentioned, the priming and activation of the NLRP3 inflammasome are regulated by multiple signaling pathways, and a number of NLRP3 inflammasome inhibitors have been developed to target these regulators. For example, taraxasterol and parthenolide suppress the activation of NLRP3 inflammasome by blocking the activation of NF-κB ( 127 ), and celastrol resolves the inflammatory response to RA through inhibition of the ROS/NF-κB/NLRP3 axis ( 128 ). In addition, β-arrestins are vital regulators of G protein-coupled receptors (GPCRs), and β-arrestin-2(βArr2) has anti-inflammatory effects in a variety of inflammation-related diseases.…”

Section: Potential Therapeutic Targets For the Nlrp3 Inflammasome In ...mentioning

confidence: 99%

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

et al. 2022

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by multi-articular, symmetrical and invasive arthritis resulting from immune system abnormalities involving T and B lymphocytes. Although significant progress has been made in the understanding of RA pathogenesis, the underlying mechanisms are not fully understood. Recent studies suggest that NLRP3 inflammasome, a regulator of inflammation, might play an important role in the development of RA. There have been increasing clinical and pre-clinical evidence showing the treatment of NLRP3/IL-1β in inflammatory diseases. To provide a foundation for the development of therapeutic strategies, we will briefly summarize the roles of NLRP3 inflammasome in RA and explore its potential clinical treatment.

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Section: Potential Therapeutic Targets For the Nlrp3 Inflammasome In ...mentioning

confidence: 99%

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

et al. 2022

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“…Celastrolis a natural triterpenoid found in Tripterygium wilfordii that has been used to treat a variety of common diseases because of its strong anti-inflammatory activity ( Jing et al, 2021 ; Zhu et al, 2021 ; Li M. et al, 2022 ). Celastrol can inhibit the upregulation of IL-6andTNF-α expression in NP cells induced by IL-1β ( Chen et al, 2017 ).…”

Section: Phytochemicals For the Treatment Of Idd By Targeting Inflamm...mentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

et al. 2022

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Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

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“…Celastrol ( Figure 3 ) triterpenoid isolated from the roots of Tripterygium wilfordii , shows a promising anti-inflammatory effect. The Chinese National Medical Products Administration has approved the use of Tripterygium wilfordii tablets for the treatment of rheumatoid arthritis: a concentration of 25–50 nM of celastrol inhibits the IL-1β release in ATP- and LPS-induced NLRP3 activation [ 48 ]. Yu and coworkers [ 49 ] reported that a dose of 125 nM of celastrol could inhibit the IL-1β release in vivo and in vitro through preventing the oligomerization of ASC and subsequently NLRP3 activity [ 49 ].…”

Section: Reported Nlrp3 Natural Product Inhibitorsmentioning

confidence: 99%

A Selective Review and Virtual Screening Analysis of Natural Product Inhibitors of the NLRP3 Inflammasome

2022

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The NLRP3 inflammasome is currently an exciting target for drug discovery due to its role in various inflammatory diseases; however, to date, no NLRP3 inhibitors have reached the clinic. Several studies have used natural products as hit compounds to facilitate the design of novel selective NLRP3 inhibitors. Here, we review selected natural products reported in the literature as NLRP3 inhibitors, with a particular focus on those targeting gout. To complement this survey, we also report a virtual screen of the ZINC20 natural product database, predicting favored chemical features that can aid in the design of novel small molecule NLRP3 inhibitors.

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Celastrol inhibits rheumatoid arthritis through the ROS-NF-κB-NLRP3 inflammasome axis

Cited by 62 publications

References 43 publications

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

A Selective Review and Virtual Screening Analysis of Natural Product Inhibitors of the NLRP3 Inflammasome

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