Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro

Jie, Fengming; Xiao, Suting; Qiao, Yang; You, Yihui; Feng, Yuan; Yu, Liang; Li, Sixin; Wu, Yanli; Li, Yanwu; Du, Qun

doi:10.1016/j.jep.2020.113243

Cited by 43 publications

(19 citation statements)

References 39 publications

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“…Previous studies have reported that pyroptosis is induced in the normal intestine or colon via activation of Casp1/GSDMD in ulcerative colitis injury (49)(50)(51) or in response to IR (18,52). A study demonstrated that pyroptosis in human colorectal cancer cells is induced by chemotherapeutic drugs, such as lobaplatin via Casp3/GSDME activation rather than Casp1/GSDMD (10).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)-induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non-coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR-induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)-448 and gasdermin E (GSDME) levels were evaluated using reverse transcription-quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR-448 and GSDME was assessed using the dual-luciferase reporter assay. Pyroptosis was examined using phase-contrast microscopy, flow cytometry, Cell Counting Kit-8 assay and lactate dehydrogenase release assay. IR dose-dependently induced GSDME-mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR-448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR-448 expression. Notably, NEAT1 knockdown suppressed IR-induced pyroptosis, full-length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR-induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR-induced pyroptosis and viability in HCT116 cells via miR-448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR-induced pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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“…In the Caspase-4/5/11-dependent non-canonical pathway, lipopolysaccharide (LPS) is recognized by human Caspase-4, human Caspase-5, and murine Caspase-11, followed by the direct processing of GSDMD by the activated Caspase-4/5/11, ultimately inducing pyroptosis [16]. Some studies have indicated that pyroptosis plays an important role in UC, as pyroptosis can prompt the release of IL-1β and IL-18 that are essential inflammatory factors for UC initiation [19][20][21]. However, other studies have shown that Caspase-1 −/− /Caspase-11 −/− mice become susceptible to colitis, which suggests a protective effect of pyroptosis against colitis [22,23].…”

Section: Introductionmentioning

confidence: 99%

Apple Polyphenols Extract (APE) Alleviated Dextran Sulfate Sodium Induced Acute Ulcerative Colitis and Accompanying Neuroinflammation via Inhibition of Apoptosis and Pyroptosis

Liu

Wang

Cui

et al. 2021

Foods

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The main aim of this study was to investigate the potent anti-apoptosis and anti-pyroptosis effects of apple polyphenols extract (APE) on dextran sulfate sodium model group (DSS)-induced acute ulcerative colitis (UC) and the protective effect of APE against acute UC-related neuroinflammation and synapse damage. Forty-three C57BL/6 male mice were randomly divided into a control group (CON), a 3% DSS model group (DSS), a 500 mg/(kg·bw·d) APE group (HAP), and a 125 (LD) or 500 (HD) mg/(kg·bw·d) APE treatment concomitantly with DSS treatment group. The results showed that APE significantly ameliorated DSS-induced acute UC through inhibiting intestinal epithelial cell (IEC) apoptosis and the Caspase-1/Caspase-11-dependent pyroptosis pathway, with increased BCL-2 protein expression and decreased protein levels of NLRP3, ASC, Caspase-1/11, and GSDND. Furthermore, APE significantly reduced acute UC-related neuroinflammation and synapse damage, supported by decreased mRNA levels of hypothalamus Cox-2 and hippocampus Gfap and also increased the mRNA levels of hypothalamus Psd-95. The increased protein expression of ZO-1 and Occludin improved the intestinal barrier integrity and improved the function of goblet cells by upregulating the protein level of MUC-2 and TTF3 accounted for the beneficial effects of APE on UC-associated neuroinflammation. Therefore, APE might be a safe and effective agent for the management of acute UC.

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“…Pyroptosis is a novel type of pro-inflammatory programmed cell death, which is different from necrosis and apoptosis and is closely associated with the activation of NLRP3 inflammasome [ 11 ]. After stimulation, NLRP3 binds to ASC to recruit Caspase-1 to form an inflammasome complex [ 20 ]. Subsequently, it is cleaved to form active IL-1β.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have also shown that the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is an important signal transduction pathway of colitis injury, playing an important role in regulating cell proliferation, differentiation and apoptosis [ 18 , 19 ]. Caspase-1 and NLRP3 are key components of inflammation, and their dysregulation promotes the production of UC-associated pro-inflammatory cytokines (interleukin-1beta (IL-1β) and IL-18) [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Zhang

Wang

Shen

et al. 2021

Aging

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Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1β) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.

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Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro

Cited by 43 publications

References 39 publications

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Apple Polyphenols Extract (APE) Alleviated Dextran Sulfate Sodium Induced Acute Ulcerative Colitis and Accompanying Neuroinflammation via Inhibition of Apoptosis and Pyroptosis

Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

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