Solasonine is a compound isolated from Solanum melongena that has anti-infection properties, and promotes neurogenesis. However, the use of solasonine for the treatment of hepatocellular carcinoma (HCC) has not yet been reported. So, the aim of this study was to assess the efficacy of solasonine for the treatment of HCC. The effects of solasonine were tested using the HCC cell lines HepG2 and HepRG. Metabolomics analysis was conducted to assess the effects of solasonine on tumor growth of nude mice xenografts using HepG2 cells. The data demonstrated that solasonine significantly suppressed proliferation of HepG2 and HepRG cells. A mouse xenograft model of HepG2 tumor formation confirmed that solasonine suppressed tumor volume and weight, and inhibited HCC cell migration and invasion, as determined with the Transwell and scratch wound assays. To further reveal the underlying regulatory mechanism, metabolomics analysis was performed. The results revealed the effects of solasonine on glutathione metabolism, including glutathione peroxidase 4 (GPX4) and glutathione synthetase (GSS). The glutathione-dependent lipid hydroperoxidase GPX4 prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death. Solasonine increased lipid ROS levels in HepG2 cells by suppression of GPX4 and GSS. However, the use of a ferroptosis inhibitor reversed solasonine-induced ROS production and cell apoptosis. Taken together, these results demonstrate that solasonine promotes ferroptosis of HCC cells via GPX4-induced destruction of the glutathione redox system.

Introduction: Obesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.Methods: Diagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data.Results and discussion: The results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population.

Amid the establishment and optimization of Connectivity Map (CMAP), the functional relationships among drugs, genes, and diseases are further explored. This biological database has been widely used to identify drugs with common mechanisms, repurpose existing drugs, discover the molecular mechanisms of unknown drugs, and find potential drugs for some diseases. Research on traditional Chinese medicine (TCM) has entered a new era in the wake of the development of bioinformatics and other subjects including network pharmacology, proteomics, metabolomics, herbgenomics, and so on. TCM gradually conforms to modern science, but there is still a torrent of limitations. In recent years, CMAP has shown its distinct advantages in the study of the components of TCM and the synergetic mechanism of TCM formulas; hence, the combination of them is inevitable.

Overuse of acetaminophen (APAP) is a major cause of drug-induced liver failure at the clinics. Apigenin (API) is a natural flavonoid derived from Matricaria chamomilla. The aim of the present study was to investigate the amelioration function of API in APAP-induced hepatotoxicity both in vitro and in vivo and investigate its potential mechanisms. Analysis results of the activities of serum alanine and aspartate aminotransferases (ALT and AST), malondialdehyde, myeloperoxidase (MPO), and reactive oxygen species (ROS) demonstrated therapeutic effects of API. MTT assay results revealed that API attenuated APAP and its metabolic product, N-acetyl-p-benzoquinone imine (NAPQI) induced cytotoxicity in a dose-dependent manner in human liver cells, L-02 cells. Subsequently, metabolomic results of cells and serum analyses demonstrated an aberrant level of carnitine palmitoyltransferase I (CPT1A). We established that API stimulated CPT1A activity in mice liver tissues and L-02 cells. Molecular docking analyses revealed potential interaction of API with CPT1A. Further investigation of the role of CPT1A in L0-2 cells revealed that API reversed cytotoxicity via the AMP-activated protein kinase (AMPK)/GSK-3β signaling pathway and compound C, which is a selective AMPK inhibitor, inhibited activation of CPT1A induced by API. API was bound to the catalytic region of AMPK as indicated by molecular docking results. In addition, compound C suppressed nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2) that is enhanced by API and inhibited the antioxidative function of API. In summary, the study demonstrates that API attenuates APAP-induced hepatotoxicity by activating the AMPK/GSK-3β signaling pathway, which subsequently promotes CPT1A activity and activates the NRF2 antioxidant pathway.