Sennoside A is a novel inhibitor targeting caspase-1

Wu, Jiasi; Lan, Yuejia; Shi, Xiaoke; Huang, Weicai; Li, Sheng; Zhang, Jizhou; Wang, Huan; Wang, Fei; Meng, Xianli

doi:10.1039/d2fo01730j

Cited by 10 publications

(6 citation statements)

References 62 publications

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“…NLRP3 Inhibitors NT0793/NT0249 (Mullard, 2019;Freeman and Swartz, 2020) b-Hydroxybutyrate (BHB) (Youm et al, 2015) MCC950 (Gordon et al, 2018) CY09 (Jiang et al, 2017) OLT1177 (Marchetti et al, 2018) Tranilast (N-[30, 40 -dimethoxycinnamoyl]-anthranilic acid, TR) (Huang et al, 2018) Oridonin (Ori) (He et al, 2018) Blood POZ-containing gene type-2 (BPO-Z) (Li et al, 2023) GSDMD Inhibitors dimethyl fumarate (DMF) (Vora et al, 2021) disulfiram (DSF) (Vora et al, 2021) Immunomodulators Anankira (Gupta, 2020;Khan, 2020) CZL-80 (Pan et al, 2022) Sennoside A (Sen A) (Wu et al, 2022) siRNA experimental trial level for other auto-inflammatory diseases (Feng et al, 2021;Idris et al, 2021;Mehta et al, 2021) Diarimalala et al 10.3389/fcimb.2023 Frontiers in Cellular and Infection Microbiology frontiersin.org…”

Section: Classification Drug Name Referencementioning

confidence: 99%

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Inflammasomes during SARS-CoV-2 infection and development of their corresponding inhibitors

Diarimalala

2023

Front. Cell. Infect. Microbiol.

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Corona Virus Disease 2019 (COVID-19) continues to be a burden for human health since its outbreak in Wuhan, China in December 2019. Recently, the emergence of new variants of concerns (VOCs) is challenging for vaccines and drugs efficiency. In severe cases, SARS-CoV-2 provokes inappropriate hyperinflammatory immune responses leading to acute respiratory distress syndrome (ARDS) and even death. This process is regulated by inflammasomes which are activated after binding of the viral spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2) receptor and triggers innate immune responses. Therefore, the formation of “cytokines storm” leads to tissue damage and organ failure. NOD-like receptor family pyrin domain containing 3 (NLRP3) is the best studied inflammasome known to be activated during SARS-CoV-2 infection. However, some studies suggest that SARS-CoV-2 infection is associated with other inflammasomes as well; such as NLRP1, absent in melanoma-2 (AIM-2), caspase-4 and -8 which were mostly found during dsRNA virus or bacteria infection. Multiple inflammasome inhibitors that exist for other non-infectious diseases have the potential to be used to treat severe SARS-CoV-2 complications. Some of them have showed quite encouraging results during pre- and clinical trials. Nevertheless, further studies are in need for the understanding and targeting of SARS-Cov-2-induced inflammasomes; mostly an update of its role during the new VOCs infection is necessary. Hence, this review highlights all reported inflammasomes involved in SARS-CoV-2 infection and their potential inhibitors including NLRP3- and Gasdermin D (GSDMD)-inhibitors. Further strategies such as immunomodulators and siRNA are also discussed. As highly related to COVID-19 severe cases, developing inflammasome inhibitors holds a promise to treat severe COVID-19 syndrome effectively and reduce mortality.

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Section: Classification Drug Name Referencementioning

confidence: 99%

“…Indeed, CZL-80 is a caspase-1 inhibitor that had successfully treated mice developing progressive ischemic stroke (PIS) (Pan et al, 2022). Recently, Sennoside A (Sen A) was identified to inhibit caspase-1 and induced the suppression of both NLRP3 and AIM-2 inflammasomes (Wu et al, 2022).…”

Section: Immunomodulatorsmentioning

confidence: 99%

Inflammasomes during SARS-CoV-2 infection and development of their corresponding inhibitors

Diarimalala

2023

Front. Cell. Infect. Microbiol.

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“… [ 83 ] Sennoside A It inactivates caspase-1 to inhibit NLRP3 and AIM2 inflammasome-involved inflammation. [ 84 ] Total extract of Abelmoschus manihot L Inhibition of caspase-8/caspase-3/NLRP3/GSDME signaling. [ 85 ] Dextmedetomidine It inhibits GSDMD by activating the PI3K/AKT/GSK3β pathway.…”

Section: Factors Affecting Rt-induced Pyroptosismentioning

confidence: 99%

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Li,

Yang,

Zhang

et al. 2024

Cell Death Discov.

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Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

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“…Moreover, a number of other compounds with different chemical skeletons such as emodin, coptisine and fraxin, all exert beneficial effect to different extents; more details are shown in Table . It is worth mentioning that emodin, coptisine and baicalin are respectively the principal contents of Rheum palmatum , Coptis chinensis and Scutellaria baicalensis , the three of which are the herb members of San-huang Xie-xin decoction (SHXXT), a well-known prescription which was documented in a famous ancient medical book, namely “Jin-Gui-Yao-Lve” . Given the fact that SHXXT is widely recognized at home and abroad for its clinical application to clear away heat and remove toxin, it will be of interest to further ascertain whether and how SHXXT modulates lung cell pyroptotic death to ameliorate ARDs induced by sepsis in a future study.…”

Section: Small-molecule Compounds From Dietary Plants Alleviate Sepsi...mentioning

confidence: 99%

Sepsis-Induced Acute Lung Injury Is Alleviated by Small Molecules from Dietary Plants via Pyroptosis Modulation

Lan

et al. 2023

J. Agric. Food Chem.

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Sepsis-induced acute respiratory distress syndrome (ARDS) has high morbidity and mortality, and it has three major pathogeneses, namely alveolar–capillary barrier destruction, elevated gut permeability, and reduced neutrophil extracellular traps (NETS), all of which are pyroptosis-involved. Due to limitations of current agents like adverse reaction superposition, inevitable drug resistance, and relatively heavier financial burden, naturally extracted small-molecule compounds have a broad market even though chemically modified drugs have straightforward efficacy. Despite increased understanding of the molecular biology and mechanism underlying sepsis-induced ARDS, there are no specific reviews concerning how small molecules from dietary plants alleviate sepsis-induced acute lung injury (ALI) via regulating pyroptotic cell death. Herein, we traced and reviewed the molecular underpinnings of sepsis-induced ALI with a focus on small-molecule compounds from dietary plants, the top three categories of which are respectively flavonoids and flavone, terpenoids, and polyphenol and phenolic acids, and how they rescued septic ALI by restraining pyroptosis.

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Sennoside A is a novel inhibitor targeting caspase-1

Abstract: The assembling of inflammasomes drive caspase-1 activation which further undertakes the proinflammatory cytokines secretion and downstream pyroptosis. Discovery of novel caspase-1 inhibitors is pivotal to develop new therapeutic means for...

Cited by 10 publications

References 62 publications

Inflammasomes during SARS-CoV-2 infection and development of their corresponding inhibitors

Inflammasomes during SARS-CoV-2 infection and development of their corresponding inhibitors

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Sepsis-Induced Acute Lung Injury Is Alleviated by Small Molecules from Dietary Plants via Pyroptosis Modulation

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