The activation of the nucleotide oligomerization domain (NOD)like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, LicoB directly binds to NEK7 and inhibits the interaction between NLRP3 and NEK7, thus suppressing NLRP3 inflammasome activation. Furthermore, LicoB exhibits protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including lipopolysaccharide (LPS)-induced septic shock, MSU-induced peritonitis and nonalcoholic steatohepatitis (NASH). Our findings indicate that LicoB is a specific NLRP3 inhibitor and a promising candidate for treating NLRP3 inflammasome-related diseases.

Using a copper nanoparticle-spaced graphene film as the anode, a newly developed lithium-ion battery exhibits a high charge/discharge capacity, an excellent reversibility, a high coulombic efficiency, and a good rate capacity.

Liver fibrosis is an abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Chronic liver injury leads to release of inflammatory cytokines and reactive oxygen species (ROS) from damaged hepatocytes, which activates hepatic stellate cells (HSCs) to secrete extracellular matrix proteins, thereby leading to fibrosis. Thus, inhibition of hepatocyte injury and HSC activation, and promotion of apoptosis of activated HSCs are important strategies for prevention of liver fibrosis. In this study, we showed that the germacrone (GER), the main component in the volatile oil of zedoary turmeric, inhibited hepatic fibrosis by regulating multiple signaling pathways. First, GER improved the cell survival rate by inhibiting the production of ROS after hepatocyte injury caused by acetaminophen (APAP). In addition, GER inhibited the activation of HSCs and expression of collagen I by blocking TGF-β/Smad pathway in LX-2 cells. However, when the concentration of GER was higher than 60 μM, it specifically induced HSCs apoptosis by promoting the expression and activation of apoptosis-related proteins, but it had no effect on hepatocytes. Importantly, GER significantly attenuated the methionine- and choline-deficient (MCD) diet-induced liver fibrosis by inhibiting liver injury and the activation of HSCs in vivo. In summary, GER can not only protect hepatocytes by reducing ROS release to avoid the liver injury-induced HSC activation, but also directly inhibit the activation and survival of HSCs by regulating TGF-β/Smad and apoptosis pathways. These results demonstrate that GER can be used as a potential therapeutic drug for the treatment of liver fibrosis.

Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention. Because the hepatotoxicity mechanism is little understood, this research strived to investigate the hepatotoxicity mechanism of Rhizoma Paridis extracts based on iTRAQ quantitative proteomics and metabonomics. The extraction solutions were administrated to rats for 7 days by gavage, and the hepatotoxicity was assessed through quantification of biochemical indexes and Oil red O staining. Additionally, the mechanism of hepatotoxicity was investigated by metabonomics based upon GC-MS and iTRAQ quantitative proteomics. The biochemical and histopathological analysis stood out that Rhizoma Paridis extract could induce liver injury, which was proved by the formation of fat droplets, the changes of mitochondrial structure, and biochemical parameters. The iTRAQ proteomics and metabonomics revealed that Rhizoma Paridis-induced hepatotoxicity was chiefly connected with the abnormal activity of mitochondrion function, which brought about oxidative stress injuries and inflammation, finally causing cell apoptosis. Collectively, we have provided previously uncharacterized hepatotoxic mechanism induced by Rhizoma Paridis and a reference to ensure its safe use in the future.Rhizoma Paridis, the roots of the Paris polyphylla Smith var. (Franch.), was first recorded in 'Shennong Herb' and Li Shizhen's 'Compendium of Materia' . The prepared Rhizoma Paridis has remarkable therapeutic effects on fractures, parotitis, hemostasis, snake bite, and abscess in the clinic for thousands of years. In addition, modern pharmacology indicated that Raw Rhizoma Paridis has beneficial impact on anti-tumor, immunity adjustment, analgesia, and anti-inflammation 1-3 . However, clinical researches regarding adverse reactions caused by Rhizoma Paridis and its preparations 4 , especially hepatotoxicity, have attracted significant attention in recent years 5 . The Chinese Pharmacopoeia clearly describes its hypotoxicity and reminds the patient and doctor to note the possible problems of orally ingesting Rhizoma Paridis and its drug preparations in high doses or over prolonged periods and when taken with other liver-damaging drugs. Despite these warnings, the mechanisms remained little known 6 .Recently, omic technologies are becoming important in vitro and in vivo tools for identifying potential hepatotoxicity mechanisms. The proteomics can identify the differentially expressed proteins that occur in a specific function, which may involve disease-or disorder-related changes in transcription, translation, transport, degradation, and covalent modification 7,8 . Metabolomics is another powerful technology for identifying a number of low-molecular-weight endogenous metabolites and assessing the dynamic variations in the biological samples 1