Corilagin Restrains NLRP3 Inflammasome Activation and Pyroptosis through the ROS/TXNIP/NLRP3 Pathway to Prevent Inflammation

Abstract

Corilagin, a gallotannin, shows excellent antioxidant and anti-inflammatory effects. The NLRP3 inflammasome dysfunction has been implicated in a variety of inflammation diseases. However, it remains unclear how corilagin regulates the NLRP3 inflammasome to relieve gouty arthritis. In this study, bone marrow-derived macrophages (BMDMs) were pretreated with lipopolysaccharide (LPS) and then incubated with NLRP3 inflammasome agonists, such as adenine nucleoside triphosphate (ATP), nigericin, and monosodium urate (MSU) crystals. The MSU crystals were intra-articular injected to induce acute gouty arthritis. Here we showed that corilagin reduced lactate dehydrogenase (LDH) secretion and the proportion of propidium iodide- (PI-)stained cells. Corilagin suppressed the expression of N-terminal of the pyroptosis executive protein gasdermin D (GSDMD-NT). Corilagin restricted caspase-1 p20 and interleukin (IL)-1β release. Meanwhile, corilagin attenuated ASC oligomerization and speck formation. Our findings confirmed that corilagin diminished NLRP3 inflammasome activation and macrophage pyroptosis. We further discovered that corilagin limited the mitochondrial reactive oxygen species (ROS) production and prevented the interaction between TXNIP and NLRP3, but ROS activator imiquimod could antagonize the inhibitory function of corilagin on NLRP3 inflammasome and macrophage pyroptosis. Additionally, corilagin ameliorated MSU crystals induced joint swelling, inhibited IL-1β production, and abated macrophage and neutrophil migration into the joint capsule. Collectively, these results demonstrated that corilagin suppressed the ROS/TXNIP/NLRP3 pathway to repress inflammasome activation and pyroptosis and suggest its potential antioxidative role in alleviating NLRP3-dependent gouty arthritis.

Role of NLRP3 in the pathogenesis and treatment of gout arthritis

“…Corilagin attenuated MSU-induced joint swelling, IL-1β production, abated macrophage and neutrophil migration into the joint capsule. It was also confirmed that corilagin suppressed the ROS/TXNIP/NLRP3 pathway to restrain inflammasome activation and macrophage pyroptosis, which may play a key role in alleviating NLRP3-dependent GA ( 83 ). A flavonoid called neoastilbin is discovered in the rhizome of the Smilax glabra plant and has been shown to have anti-inflammatory properties.…”

The role of ROS-induced pyroptosis in CVD

“…In a similar experiment, Zou Y et al found that luteolin inhibited the generation of ROS through Nrf2 activation and NF-κB inactivation, thereby preventing the pyroptosis of THP-1 macrophages ( 42 ). In addition, corilagin, punicalin, and exosomes derived from M2 macrophages can all inhibit pyroptosis by reducing the production of ROS ( 31 , 43 , 44 ). Cong et al found that electrical stimulation inhibited Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation ( 45 ).…”

The role of NLRP3 inflammasome-mediated pyroptosis in ischemic stroke and the intervention of traditional Chinese medicine

“…All known PAMPs and DAMPs trigger the production of ROS, which can then induce the assembly of the NLRP3 inflammasome. High levels of ROS promote the dissociation of the oxidationreduction sensitive signal complex TXNIP, which is translocated from the nucleus to the cytoplasm (Luo et al, 2022). TXNIP binds to the NLRP3 receptor domain (mainly LRR domain), thus inducing the activation of NLRP3 inflammasome (Chen D et al, 2018).…”