Mechanistic insights into aniline-induced liver injury: Role of the mmu_circ_26984/Myh9/NLRP3 axis and modulation by N-acetylcysteine.

Aniline is a widely used chemical. Chronic or high-dose exposure to aniline can lead to hepatocellular damage. Although the hepatic pathogenicity of aniline has been established in previous studies, studies involving pathogenic genes during aniline-induced liver injury are limited. Our study first discovered and identified the role and mechanism underlying a new circRNA mmu_circ_26984 in aniline-induced chemical liver injury. Further, we discuss the protective effect of N-acetylcysteine (NAC) in this pathway. After constructing in vitro and in vivo models of aniline treatment, we screened the circRNA with significant differences in expression in AML12 cells from control and aniline-treated groups by circRNA microarray analysis. Next, using RNA pulldown, liquid chromatography-mass spectrometry (LC-MS), and RNA immunoprecipitation, we analyzed the relationship between mmu_circ_26984 and myosin heavy chain 9 (Myh9). Subsequently, we determined the specific mechanism of action of mmu_circ_26984 and Myh9 in aniline-induced liver injury and the protective effect of NAC against aniline-induced liver injury process using Cell Counting Kit-8, Western blot, RNA extraction, a reverse transcription quantitative polymerase chain reaction (RT-qPCR), fluorescence in situ hybridization, immunohistochemistry, and immunofluorescence. The expression of mmu_circ_26984 was significantly increased in liver tissues and AML12 cells of aniline-treated mice compared with the control group. This high expression of mmu_circ_26984 increased the expression of injury-related inflammatory factors, such as NLRP3, Caspase-1, IL-18, and IL-1ß in vivo and ex vivo, which exacerbated the level of liver injury. The interaction of mmu_circ_26984 with Myh9 also affected the course of liver injury. Mmu_circ_26984 overexpression and reduced treatment affected the levels of Myh9 expression in AML12 cells, as well as downstream inflammatory factors associated with injury, such as NLRP3. In addition, NAC reduced the process of liver injury mediated by the mmu_circ_26984/Myh9/NLRP3 axis. In conclusion, mmu_circ_26984 is a potential molecular marker and therapeutic target in the process of aniline-induced liver injury that can mediate aniline-exposure-induced liver injury via modulation of the mmu_circ_26984/Myh9/NLRP3 axis, and NAC can effectively attenuate the effect of this liver injury.

STAT3: A key regulator in liver fibrosis.

Janus protein tyrosine kinase (JAK) has the ability to activate signal transducer and activator of transcription (STAT). STAT3 is a valued member of the JAK/STAT signaling pathway. In recent years, several studies have documented that STAT3 is closely related to the occurrence and development of liver fibrosis caused by various factors. Activation of STAT3 can play anti- or pro-inflammatory roles in the pathogenesis of liver fibrosis. This article reviewed the recent studies on STAT3 in the development of various liver fibrosis to find a more effective method to relieve and cure liver diseases, such as hepatitis B virus (HBV), non-alcoholic fatty liver disease (NAFLD), schistosomiasis, and chemical liver injury.

Research Progress in Treatment of Chemical Liver Injury with Chinese Medicine Based on Metabolomics / 中国实验方剂学杂志

Liver， as a critical organ of metabolism and detoxification， can be damaged by viral infection， drug abuse， and heavy drinking. Liver diseases pose a serious threat to people's health and life in China.At present， drug therapy has been primarily adopted clinically in the treatment of the liver injury.In-depth investigation of the mechanism of liver-protective drugs is of great significance to the prevention and treatment of clinical liver diseases.In recent years， with the development of the medical industry in China， an increasing number of studies have focused on the treatment of liver injury with Chinese medicine.Compared with western medicine， Chinese medicine is advantageous in few side effects and overall regulation， which plays a pivotal role in liver protection.However， its underlying mechanism in liver protection still needs to be further studied due to its complex compositions and diverse targets.Metabolomics， a new approach to studying the metabolic pathway of biological systems， provides integral and systematic views in the investigation of liver protection with Chinese medicine. By virtue of metabolomics， the mechanism of Chinese medicine in multi-target and multi-pathway liver protection can be analyzed comprehensively， and the corresponding biomarkers can also be screened out. The authors analyzed the studies of the treatment of chemical liver injury models induced by carbon tetrachloride （CCl4）， dimethylnitrosamine （DMN）， α-naphthyl isothiocyanate （ANIT）， and alcohol by Chinese medicinal compounds， single herbal medicines， and monomers of Chinese medicine based on metabolomics， and summarized the biomarkers and related metabolic pathways of Chinese medicine in the intervention of each type of liver injury， aiming at providing a reference for the further research and clinical application in the treatment of different types of liver injuries by Chinese medicine.

Protective effect of Portulaca oleracea L. extract on acute liver injury induced by carbon tetrachloride in mice and its chemical composition analysis / 药学实践杂志

Objective To investigate the protective effect of the ethanol extract of Portulaca oleracea L. on acute liver injury induced by carbon tetrachloride in mice, and to analyze its effective components. Methods 80% ethanol purslane extract was centrifuged, vacuum distillated and vacuum dried into whole plant extract, supernatant extract and precipitated extract. Eighty ICR male mice were randomly divided into 8 groups: control group, liver injury model group, whole plant extract low-dose group, high-dose group, supernatant extract low-dose group, high-dose group, precipitation extract low-dose group, and high-dose group. After oral administration of distilled water or three kinds of purslane extract suspensions at different doses for 1 week, olive oil or CCl4 olive oil solution were injected subcutaneously respectively. After 16 hours, serum was collected to detect the levels of ALT, AST and IL-6 to evaluate the protective effect of purslane on acute liver injury. Ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the effective components of purslane extract. Results Compared with the model group, the levels of serum AST, ALT and IL-6 in high-dose whole plant extract group were significantly reduced. The serum ALT level of mice in the high-dose precipitation extract group was significantly reduced (P<0.05). The serum IL-6 level was decreased, but there was no significant difference. There were no significant changes in the levels of serum AST, ALT and IL-6 in the other intervention groups. 15 main components such as malic acid, citric acid, leucine, isoleucine, adenosine, succinic acid, genistein, tyrosine and phenylalanine were identified by UPLC-Q-TOF/MS. Conclusion Purslane whole plant ethanol extract has hepatoprotective and anti-inflammatory effects on CCl4 acute liver injury mice, which may be a combined effect of 15 active components.

Analysis on formula characteristics of health food with auxiliary protective function in chemical liver injury / 中草药

Through searching the information of chemical liver injury protection function of health food on the State Food and Drug Administration website and using Microsoft Excel 2016 software and Traditional Chinese Medicine Inheritance System, to analyze formula characteristics of health food and provide the basis for the formulation of health food with auxiliary protective function in chemical liver injury and the development of the product. A total of 325 kinds of health food were collected, of which 282 (86.8%) health food formulations contained Chinese materia medica (CMM) raw materials. The number of health food with one single health care function and two healthy functions was 192 and 133, respectively. In terms of dosage forms, there were 156 capsules, which account for about half of the total. Moreover, there were 21 kinds of CMM raw materials with more than 18 of the use frequency (f) and accumulated 768 times (73%). Nine new prescriptions were obtained by unsupervised entropy hierarchical clustering. The CMM is widely used in the health food which has the auxiliary protective function in the chemical liver injury. The choice of dosage forms is based on convenience of taking and carrying. Five commonly used functional ingredients are total flavonoids, crude polysaccharides, puerarin, total saponins, and taurine. The choice of CMM is basically consistent of the principle of traditional Chinese medicine treatment of chemical liver disease which are detoxification, strengthening the body resistance, promoting blood circulation, clearing away heat, dehumidification and so on. The most commonly used drugs are anti-alcoholismic drugs, tonic medicine, blood-activating and stasis-resolving drugs, heat-clearing drugs, and damp-draining diuretic. Nine new prescriptions found by software must be further evaluated in combination with the theory and practice of Chinese medicine and comprehensive analysis.

Protection of Sanqibaogan Capsules against the acute and chemical liver injury in mice / 中成药

AIM: To observe the liver protective effect of Sanqishentai Capsules (Radix Notoginseng, Herba Artemisiae Scopariae and Fructus Ziziph:Jujubae, etc.) in order to develop a series of compound Notoginseng. METHODS: By injecting CCl 4 in mouse's abdomen to cause the liver injury as model. The effect of the index of ALT, AST was mensurated that use the small, middle, big dosage of Sanqibaogan Capsules, at the same time the liver was examined in pathologic histology. RESULTS: The different dosages of Sanqishentai Capsules could obviously reduce the serum ALT, AST and the pathologic injury of the liver cells caused by CCl 4. CONCLUSION: Sanqibaogan Capsules have the obvious protection to the ocute and chemical liver injury of the mice.