Inflammasome mediates the activation of caspase-1, which promotes the secretion of proinflammatory cytokines. In this work, we aimed to investigate whether natural compounds from a Traditional Chinese Medicine prescription called San-Huang-Xie-Xin-Tang exert its clinical efficacy by inhibiting inflammasome activation and the underlying mechanism. The inhibitory effects of compounds on caspase-1 were evaluated in recombinant expressed caspase-1 protein and macrophages. Molecular docking was conducted to examine the interaction between compounds and caspase-1. The effects of the compounds on pro-inflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mechanism of the compounds on nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome activation was investigated in macrophages. The anti-inflammasome effects of compounds were examined in mice stimulated by lipopolysaccharide (LPS) and monosodium urate crystal (MSU). Coptisine was the most potent inhibitor of caspase-1 in the San-Huang-Xie-Xin-Tang prescription. Coptisine adopted a favorable conformation at the active site of caspase-1. Coptisine significantly attenuated mature interleukin (IL)-1β secretion in RAW264.7 macrophages stimulated with LPS plus ATP, nigericin, or MSU, by blocking caspase-1 activation. Coptisine not only prevented NLRP3 inflammasome assembly by affecting the binding between pro-caspase-1 and apoptosis-associated speck-like protein containing a CARD, but also inhibited inflammasome priming by decreasing NLRP3 expression through inactivation of the nuclear factor-κB pathway. Moreover, coptisine prevented LPS-mediated IL-1β production and MSU-mediated mice paw edema by blocking NLRP3 inflammasome activation in vivo. Coptisine blocks NLRP3 inflammasome activation by inhibiting caspase-1 and may be useful for treating NLRP3 inflammasome-involved gouty arthritis.
Background: Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM.
Idiopathic inflammatory myopathies (IIM) are a group of systemic autoimmune diseases characterized by muscle weakness and elevated serum creatine kinase levels. Recent research has highlighted the role of the innate immune system, particularly inflammasomes, in the pathogenesis of IIM. This review focuses on the role of inflammasomes, specifically NLRP3 and AIM2, and their associated proteins in the development of IIM.
Recent research indicates that the activation of the NLRP3 inflammasome is crucial in the development of diabetic kidney disease (DKD). Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has been noted for its anti-inflammatory properties in DKD. However, the specific mechanisms are not yet fully understood.
Background: Pyroptosis is inflammation-associated programmed cell death triggered by activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, which plays a crucial role in acute soft tissue injury (ASTI). This study aimed to explore whether methyltransferase-like 3 (METTL3) can regulate NLRP3 expression through N6-methyladenosine (m6A) modification to mediate endothelial cell pyroptosis and thus affect soft tissue injury.
Methods: An experimental ASTI rat model was created by inducing muscle injury through striking the rat muscle.
Autophagy is a physiologically regulated cellular process orchestrated by autophagy-related genes (ATGs) that, depending on the tumor type and stage, can either promote or suppress tumor growth and progression. It can also modulate cancer stem cell maintenance and immune responses. Therefore, targeted manipulation of autophagy may inhibit tumor development by overcoming tumor-promoting mechanisms.
