Context Astragaloside IV (AS-IV) is extracted from Astragalus membranaceus (Fisch.) Bunge (Fabaceae). However, its effects on endothelial cell injury remain unclear. Objective To investigate the mechanisms underlying the effects of AS-IV on lipopolysaccharide (LPS)-induced endothelial injury in vitro . Materials and methods Human umbilical vein endothelial cells (HUVECs) were pre-treated with AS-IV (100 µmol/mL), 4-hydroxy-3-methoxyacetophenone (APO, 10 µmol/mL), N -acetylcysteine (NAC, 50 µmol/mL) and Ac-YVAD-cmk (AC, 5 µmol/mL) for 2 h before 1 μg/mL LPS 24 h exposure. Untreated cells cultured without any exposure were used as controls. Cell viability, reactive oxygen species (ROS) and pyroptosis assays were performed. The pyroptosis related proteins were detected by western blot. Results The rate in late pyroptosis (Q2-2) of AS-IV (13.65 ± 0.74%), APO (13.69 ± 0.67%) and NAC (15.87 ± 0.46%) groups was lower than the LPS group (21.89 ± 0.66%, p < 0.05), while the rate in early pyroptosis (Q2-4) of AS-IV group (12.00 ± 0.26%) was lower than other groups ( p < 0.05). The expression of NOX4, GSDMD, NLRP3, ASC and caspase-1 decreased after AS-IV, NAC or AC intervention ( p < 0.05). The ROS production in AS-IV (4664 ± 153.20), APO (4094 ± 78.37), NAC (5103 ± 131.10) and AC (3994 ± 102.50) groups was lower than the LPS (5986 ± 127.30) group, while the mitochondrial BCL2/BAX protein expression ratio increased in AS-IV, APO and NAC groups ( p < 0.05). Discussion and conclusions AS-IV suppressed pyroptosis in LPS-activated HUVECs by inducing ROS/NLRP3-mediated inhibition of the inflammatory response, providing a scientific basis for clinical applications of AS-IV.
Objective. This research aimed at better understanding the histopathological development of precancerous lesions of gastric cancer (PLGC) and organelle ultrastructure changes. Methods. Sprague-Dawley rats were randomly assigned to the model and control groups. Model rats drank N-methyl-N′-nitro-N-nitrosoguanidine solution, while control rats drank pure water ad libitum. At 1, 3, 5, 6, and 8 months after the start of feeding, eight rats were randomly chosen from each group, and gastric mucosa tissues were removed for histopathological analysis. H&E staining was applied to analyze the pathological histological structure of the rat gastric mucosa via a light microscope, and the ultrastructural changes were observed via a transmission electron microscope. Results. Gastric mucosal pathologies of model rats such as mucosal atrophy, intestinal metaplasia, inflammatory lesions, and even intraepithelial neoplasia deteriorated over time. The endoplasmic reticulum gap widened, the mitochondrial endothelial cristae were disrupted, the nuclear membrane thickened, and chromatin condensed with heterotypic alterations in the main and parietal cells. Additionally, endothelial cell enlargement and thickening of the microvascular intima were seen. Conclusion. Our research showed that the PLGC progression of rats is correlated with the pathological alteration axis of “normal gastric mucosa-gastric mucosa inflammatory changes-intestinal metaplasia with mild dysplasia-moderate to severe dysplasia.” Ultrastructure analysis of model rats is compatible with the structural changes in the gastric mucosa with spleen deficiency and blood stasis. The pathological evolutionary axis and ultrastructural analysis are helpful for evaluating potential novel herbal therapies for PLGC.
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