Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation

Mai, Chu-Tian; Wu, Mei‐Mei; Wang, Chunli; Su, Zi-Ren; Cheng, Yuanyuan; Zhang, Xiaojun

doi:10.1016/j.molimm.2018.10.015

Cited by 142 publications

(72 citation statements)

References 33 publications

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“…Therefore, a Parkin-dependent clearance of p62-bound damaged mitochondria reduces NLRP3 inflammasome activation by NLRP3 activators in macrophages ( 86 ). This is supported by increasing number of studies demonstrating that impaired mitophagy enhances NLRP3 activation, whereas induction of mitophagy reduces NLRP3 activation ( 87 – 90 ). However, reduction of autophagy by itself does not seem to be sufficient to trigger inflammasome activation in the absence of NLRP3 activators ( 41 , 82 ).…”

Section: Autophagy Regulates Nlrp3 Inflammasome Activationmentioning

confidence: 79%

Interplay Between NLRP3 Inflammasome and Autophagy

2020

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The NLRP3 inflammasome is cytosolic multi-protein complex that induces inflammation and pyroptotic cell death in response to both pathogen (PAMPs) and endogenous activators (DAMPs). Recognition of PAMPs or DAMPs leads to formation of the inflammasome complex, which results in activation of caspase-1, followed by cleavage and release of pro-inflammatory cytokines. Excessive activation of NLRP3 inflammasome can contribute to development of inflammatory diseases and cancer. Autophagy is vital intracellular process for recycling and removal of damaged proteins and organelles, as well as destruction of intracellular pathogens. Cytosolic components are sequestered in a double-membrane vesicle—autophagosome, which then fuses with lysosome resulting in degradation of the cargo. The autophagy dysfunction can lead to diseases with hyperinflammation and excessive activation of NLRP3 inflammasome and thus acts as a major regulator of inflammasomes. Autophagic removal of NLRP3 inflammasome activators, such as intracellular DAMPs, NLRP3 inflammasome components, and cytokines can reduce inflammasome activation and inflammatory response. Likewise, inflammasome signaling pathways can regulate autophagic process necessary for balance between required host defense inflammatory response and prevention of excessive and detrimental inflammation. Autophagy has a protective role in some inflammatory diseases associated with NLRP3 inflammasome, including gouty arthritis, familial Mediterranean fever (FMF), and sepsis. Understanding the interregulation between these two essential biological processes is necessary to comprehend the biological mechanisms and designing possible treatments for multiple inflammatory diseases.

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Section: Autophagy Regulates Nlrp3 Inflammasome Activationmentioning

confidence: 79%

Interplay Between NLRP3 Inflammasome and Autophagy

2020

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“…Arctigenin acts to inhibit NLRP3 inflammasome activation via SIRT1, which functions to suppress the expression of inflammatory genes [73]. Palmatine was found to facilitate a specialised autophagy pathway, the PINK1/Parkin-driven mitophagy, which inactivates NLRP3 in macrophages [74]. Formononetin was described to promote the expression of epithelial cell tight junctions, which are prominently reduced in DSS-induced colitis, and maintained the colonic epithelial barrier [75].…”

Section: The Nlrp3 Inflammasome and Ibdmentioning

confidence: 99%

Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

2020

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Inflammation is a hallmark in many forms of cancer; with colitis-associated colorectal cancer (CAC) being a progressive intestinal inflammation due to inflammatory bowel disease (IBD). While this is an exemplification of the negatives of inflammation, it is just as crucial to have some degree of the inflammatory process to maintain a healthy immune system. A pivotal component in the maintenance of such intestinal homeostasis is the innate immunity component, inflammasomes. Inflammasomes are large, cytosolic protein complexes formed following stimulation of microbial and stress signals that lead to the expression of pro-inflammatory cytokines. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been extensively studied in part due to its strong association with colitis and CAC. The aryl hydrocarbon receptor (AhR) has recently been acknowledged for its connection to the immune system aside from its role as an environmental sensor. AhR has been described to play a role in the inhibition of the NLRP3 inflammasome activation pathway. This review will summarise the signalling pathways of both the NLRP3 inflammasome and AhR; as well as new-found links between these two signalling pathways in intestinal immunity and some potential therapeutic agents that have been found to take advantage of this link in the treatment of colitis and CAC.

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“…Palmatine, an isoquinoline alkaloid distributed in many botanical families, has been reported to possess multiple pharmaceutical and biological activities, involving its antibacterial (Chae et al 1999), antiviral (Jia et al 2010), gastroprotective (Wang et al 2017) and anticolitis activities (Mai et al 2019), and has been used in gastritis and peptic ulcer treatment (Zhou et al 2017). Palmatine has also been shown to increase the effects of available antibiotics and decrease the emergence of multi-drug resistant (MDR) bacteria (Aghayan et al 2017) and possesses promising therapeutic potential against cardiac hypertrophy (Yuan et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Comparative proteomics analysis indicates that palmatine contributes to transepithelial migration by regulating cellular adhesion

Wang

Feng

Xin

et al. 2020

Pharmaceutical Biology

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Context: Palmatine, a biologically active isoquinoline alkaloid, possesses multiple pharmaceutical activities against mucosal infection and inflammation. Objective: There are no reports about the influence of palmatine on uterine mucosal epithelial cells. Materials and methods: We used proteomics to analyse differentially expressed proteins (DEPs) in goat endometrial epithelial cells (EECs) stimulated by lipopolysaccharide (LPS, 5 lg/mL, the dosage can induce inflammatory response, according to our previous study) for 12 h and then treated with palmatine (80 lg/ mL) for 8 h; the dosage was selected based on MTT assay. The EECs without any treatment were used as controls. Every group was treated in triplicate. Results: A total of 428 DEPs in LPS-stimulated group and 486 DEPs in the palmatine-treated group were identified. Functional annotation analysis showed that palmatine mainly regulated the protein expression of structural molecules involved in the response to stimuli. Pathway analysis showed that cell adhesion molecule (CaM) pathways were most significant enriched due to palmatine treatment. Junction adhesion molecule 1 (JAM1), nectin 1 (NECT1) and cadherin 5 (CDH5), which play important roles in the transepithelial migration (TEpM) of leukocytes, were significantly downregulated by palmatine. Meanwhile, other proteins essential to the maintenance of cell adhesion and those that facilitate leukocyte migration were upregulated after palmatine treatment. Discussion and conclusions: The results suggested that palmatine regulates the expression of CaMs to affect TEpM during uterine mucosal inflammation and provides novel insight to understanding and developing palmatine pharmacology. Palmatine is a promising drug for treatment of mucosal inflammation.

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Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation

Cited by 142 publications

References 33 publications

Interplay Between NLRP3 Inflammasome and Autophagy

Interplay Between NLRP3 Inflammasome and Autophagy

Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

Comparative proteomics analysis indicates that palmatine contributes to transepithelial migration by regulating cellular adhesion

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