The incidence and prevalence of inflammatory bowel disease (IBD) increases steadily worldwide. There is an urgent need for effective and safe IBD therapies. Accelerated resolution of inflammation is a new strategy for the management of inflammatory diseases. For effective and safe IBD treatment, herein a smart nanotherapy (i.e. oxidation‐responsive nanoparticles containing a proresolving annexin A1‐mimetic peptide Ac2‐26, defined as AON) is developed, which can release packaged Ac2‐26, in response to highly expressed reactive oxygen species (ROS) at diseased sites. AON effectively protects Ac2‐26 from degradation in the enzyme‐rich environment of the gastrointestinal tract. By delivering this nanotherapy to the inflamed colons of mice with IBD, site‐specific release and accumulation of Ac2‐26 in response to high levels of ROS at the inflammatory sites are achieved. Mechanistically, the Ac2‐26‐containing, oxidation‐labile nanotherapy AON effectively decreases the expression of proinflammatory mediators, attenuates trafficking and infiltration of inflammatory cells, promotes efferocytosis of apoptotic neutrophils, and increases phenotypic switching of macrophages. Therapeutically, AON reduces symptoms of inflammation, accelerates intestinal mucosal wound healing, reshapes the gut microbiota composition, and increases short‐chain fatty acid production. Additionally, oral delivery of this nanomedicine shows excellent safety profile in a mouse model, conferring the confidence for further development of a targeted precision therapy for IBD and other inflammatory diseases.

Increasing evidence has demonstrated that inflammatory response plays a crucial role in the pathogenesis of secondary injury following blast-induced traumatic brain injury (bTBI). Propofol, a lipid-soluble intravenous anesthetic, has been shown to possess therapeutic benefit during neuroinflammation on various brain injury models. Recent findings have proved that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome involved in the process of the inflammatory response following brain trauma, may probably be a promising target in the treatment of bTBI. Rats were randomly divided into six groups (n = 8): normal group; bTBI-12 and 24 h group; bTBI-12 h and bTBI-24 h group treated with propofol; and bTBI treated with control dimethyl sulfoxide (DMSO) group. The effect of propofol on the expression and activation of NLRP3 inflammasome and the degree of oxidative stress and inflammatory cascades, as well as the brain trauma biomarkers were evaluated in rats suffering from bTBI. The enhanced expressions and activation of NLRP3 inflammasome in the cerebral cortex of bTBI rats were substantially suppressed by the administration of propofol, which was paralleled with the decreased oxidative stress, cytokines production, and the amelioration of cerebral cortex damage. Our results have, for the first time, revealed that over-activation of NLRP3 inflammasome in the cerebral cortex may be involved in the process of neuroinflammation during the secondary injury of bTBI in rats. Propofol might relieve the inflammatory response and attenuate brain injury by inhibiting ROS and reluctant depressing NLRP3 inflammasome activation and pro-inflammatory cytokines maturation.

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Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.

Increasing evidence has demonstrated that reactive oxygen species (ROS) induces oxidative stress and plays a crucial role in the pathogenesis of acute pancreatitis (AP). Hydrogen-rich saline (HRS), a well-known ROS scavenger, has been shown to possess therapeutic benefit on AP in many animal experiments. Recent findings have indicated that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, an intracellular multiprotein complex required for the maturation of interleukin- (IL-) 1β, may probably be a potential target of HRS in the treatment of AP. Therefore, in this study, we evaluated the activation of NLRP3 inflammasome and meanwhile assessed the degree of oxidative stress and inflammatory cascades, as well as the histological alterations in mice suffering from cerulein-induced AP after the treatment of HRS. The results showed that the activation of NLRP3 inflammasome in AP mice was substantially inhibited following the administration of HRS, which was paralleled with the decreased NF-κB activity and cytokines production, attenuated oxidative stress and the amelioration of pancreatic tissue damage. In conclusion, our study has, for the first time, revealed that inhibition of the activation of NLRP3 inflammasome probably contributed to the therapeutic potential of HRS in AP.

The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1β, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubiquitination, a non-transcriptional priming signal of NLRP3 in response to the stimulation of LPS. Additionally, the removal of mtROS by H2 reduced the generation of oxidized mitochondrial DNA and consequently decreased its binding to NLRP3, thereby inhibiting the NLRP3 inflammasome activation. Our findings have, for the first time, revealed the novel mechanism underlying the inhibitory effect of molecular hydrogen on LPS-caused NLRP3 inflammasome activation, highlighting the promising application of this new antioxidant in the treatment of LPS-associated inflammatory pathological damage.

Green tea has been considered as a health-promoting beverage and is widely consumed worldwide. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol derived from green tea leaves with potent antioxidative and chemopreventive...

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