Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and scientific studies consistently report that NAFLD development can be accelerated by oxidative stress. Oxidative stress can induce the progression of NAFLD to NASH by stimulating Kupffer cells, hepatic stellate cells, and hepatocytes. Therefore, studies are underway to identify the role of antioxidants in the treatment of NAFLD. In this review, we have summarized the origins of reactive oxygen species (ROS) in cells, the relationship between ROS and NAFLD, and have discussed the use of antioxidants as therapeutic agents for NAFLD.

BackgroundTo comprehensively evaluate the diagnostic value of serum cartilage oligomeric matrix protein (COMP) and chondroitin sulfate 846 epitope (CS846) biomarkers in osteoarthritis (OA), longitudinal and combined measurement of serum COMP and CS846 were performed at different stages in the pathological process of OA in a rat model of anterior cruciate ligament transection (ACLT).MethodsSixty male Sprague-Dawley rats were randomly divided into two groups, including a model group (n = 30) and a control group (n = 30). Rat models were established by ACLT surgery, and sham operations were performed on rats in the control group. Prior to surgery and at 2, 4, 6, 8, and 10 weeks after ACLT surgery, serum levels of COMP and CS846 biomarkers were determined using an enzyme-linked immunosorbent assay approach. Five rats per group were euthanized at 2, 4, 6, 8, and 10 weeks after surgery, after which tibial plateau specimens were collected. Macroscopic observation and histological examination were employed for rat tibial plateau. Histological changes in articular cartilage were evaluated according to Osteoarthritis Research Society International (OARSI) scoring criteria. The area under the curve (AUC) of COMP, CS846, and combined biomarkers was compared using receiver operating characteristic (ROC) curve.ResultsWithin 10 weeks after surgery, serum levels of COMP and CS846 in the model group were significantly higher when compared to those in the control group. Moreover, a significant correlation was observed between changes in COMP and CS846 levels. At each time point, macroscopic observations and OARSI scores were significantly increased in the development of OA. The AUC of combined biomarkers was higher compared to that of COMP and CS846 alone. Finally, a positive relationship was found between levels of COMP and CS846 and the OARSI score.ConclusionsIn this study, we found that combined detection of serum CS846 and COMP levels can be used for diagnosis and monitoring of OA progression.

Nonalcoholic fatty liver disease (NAFLD) is becoming one of the most common chronic liver diseases in the world. One of the features of NAFLD is hepatic fat accumulation, which further causes hepatic steatosis, fibrosis, and inflammation. Saponins, the major pharmacologically active ingredients isolated from Panax notoginseng, contain several ginsenosides, which have various pharmacological and therapeutic functions. However, the ginsenoside-specific molecular mechanism of saponins in NAFLD remains unknown. This study aimed to elucidate the effects of ginseng saponin extract and its ginsenosides on hepatic steatosis, fibrosis, and inflammation and their underlying action mechanism in NAFLD. Mice were fed a fast food diet (FFD) for 16 weeks to induce NAFLD and then treated with saponin extract (50 or 150 mg/kg) for the remaining nine weeks to determine the effects of saponin on NAFLD. Saponin extract administration significantly alleviated FFD-induced hepatic steatosis, fibrosis, and inflammation. Particularly, saponin extract, compared with conventional red ginseng, contained significantly increased amounts of ginsenosides (Rh1 (10.34-fold) and Rg2 (7.1-fold)). In vitro Rh1 and Rg2 treatments exerted an anti-steatotic effect in primary hepatocytes, an antifibrotic effect in hepatic stellate cells, and anti-inflammatory and pro-mitophagy effects in immortalized mouse Kupffer cells. Mechanistically, saponin extract alleviated lipopolysaccharide-induced NLRP3 inflammasome activation by promoting mitophagy. In conclusion, saponin extract inhibited inflammation-mediated pathological inflammasome activation in macrophages, thereby preventing NAFLD development. Thus, saponin extract administration may be an alternative method for NAFLD prevention.

Osteoarthritis is a chronic joint disease which has a serious impact on the health and quality of life of affected humans and animals. As an inhibitor of inducible nitric oxide synthase (iNOS), aminoguanidine (AG) displays anti-inflammatory effects. The purpose of the present study was to investigate the effect of AG on the expression of iNOS and cyclooxygenase-2 (COX-2), and the activity of the NF-κB signaling pathway in rat chondrocytes stimulated by interleukin-1β (IL-1β). The viability of chondrocytes treated with AG (0.3, 1 or 3 mM) alone was determined using a Cell Counting Kit-8 assay. Subsequently, the chondrocytes were treated with either 10 ng/ml IL-1β alone, or co-treated with increasing concentrations of AG (0.3, 1 or 3 mM) and 10 ng/ml IL-1β. The protein levels of COX-2, iNOS, phosphorylated (p)-p65, p65, p-NF-κβ inhibitor α (IκBα), IκBα, p-inhibitor of NF-κβ-β (IKKβ) and IKKβ were evaluated by western blotting. NF-κB translocation was determined by immunofluorescence analysis. Western blotting and reverse transcription-quantitative PCR were used to detect expression levels of relevant proteins/genes. The results suggested that the inhibitory effect of AG on the protein and gene expression levels of iNOS and COX-2 in IL-1β-treated chondrocytes was dose-dependent. In addition, AG decreased the level of phosphorylation of IKKβ, IκBα and NF-κB p65, the degradation of IKKβ, IκBα and p65, and the translocation of NF-κB in IL-1β-stimulated chondrocytes. The most significant inhibitory effect of AG was observed at a concentration of 1 mM. Therefore, the present study suggested that AG may serve as a potential agent to reduce the inflammatory response of chondrocytes stimulated by IL-1β.

Osteoarthritis (OA) is characterized by progressive degeneration of cartilage, formation of cartilage at the cartilage edge, and remodeling of the subchondral bone. Pro-inflammatory cytokines [e.g., interleukin (IL)-1β] that induce inflammation and promote chondrocyte damage induce OA. Currently, the diagnosis of OA is commonly based on imaging examinations (e.g., X-ray) and evaluations of clinical symptoms; however, biomarkers that can effectively diagnose OA are currently not available. By studying the mechanism underlying OA cartilage injury and changes in the concentrations of the biomarkers procollagen type II carboxy-terminal propeptide (PIICP), collagen type-II C-telopeptide fragments (CTX-II), and type II collagen cleavage neoepitope (C2C) during pathogenesis, the present study established a theoretical basis for the evaluation and early diagnosis of OA. In an experiment, 10 ng/ml IL-1β was used to the treat chondrocyte-induced OA models in vitro for 0, 12, 24 and 48 h. Western blotting was used to detect the expression levels of matrix metalloproteinase (MMP)-3, MMP-13, and inducible nitric oxide synthase (iNOS) protein at each time-point. The concentrations of CTX-II, C2C, and PIICP in the cell culture supernatant were detected by ELISA kit. A biochemical kit was used to detect changes of nitric oxide (NO) in the cell culture supernatant. In addition, chondrocytes were treated with 10 ng/ml IL-1β for 0, 30, 60 and 90 min and the translocation and phosphorylation of the NF-κB pathway were investigated by western blotting. Following IL-1β stimulation, the NF-κB pathway was activated to increase the expression levels of MMPs and iNOS synthesis downstream of the pathway, resulting in an increased degradation of type II collagen (Col II). To sum up, pro-inflammatory IL-1β induced an OA chondrocyte model. During the development of OA, the expression of MMPs and NO increased and Col II was degraded.