Background:Astragalus polysaccharide extract (APS) has been shown to exhibit antioxidant and anti-inflammatory potential in the treatment of several diseases. However, whether APS could protect against renal damage in hypertensive mice is unknown.Methods: Hematoxylin and eosin staining, immunohistochemistry, real-time polymerase chain reaction, and Western blotting were used to investigate the effect of APS on the renal damage in deoxycorticosterone acetate- (DOCA) salt- and angiotensin II- (Ang II-) induced hypertensive mice and to elucidate the underlying mechanisms.Results: Our data demonstrated that APS significantly reduced blood pressure in DOCA-salt- and Ang II-treated mice. Furthermore, APS reduced the inflammatory response and renal fibrosis, thereby improving renal function. Furthermore, the levels of serum creatinine, urea nitrogen, and uric acid increased in DOCA-salt-treated mice, alleviated by APS administration. At the molecular level, DOCA-salt and Ang II increased the mRNA levels of IL-1β, IL-6, α-SMA, collagen I, and collagen III, while APS significantly inhibited these effects. APS inhibited the TGF-β1/ILK signaling pathway, which was activated in hypertensive mice due to the administration of DOCA-salt.Conclusion: Our results suggest that APS plays a beneficial role in improving renal dysfunction in hypertensive mice.

Oxysterols are compounds generated through oxidative reactions involving cholesterol and other steroid molecules. They play a crucial role in the tumor immune microenvironment by interacting with molecules such as the cell membrane receptor EBI2 and nuclear receptors like LXR and PXR. This interaction regulates immune cell signaling pathways, affecting proliferation, apoptosis, migration, and invasion in tumor-related processes. Activating these receptors alters the function and behavior of immune cells-such as macrophages, T cells, and dendritic cells-within the tumor microenvironment, thus promoting or inhibiting tumor development. Certain oxidized steroids can increase both the number and activation of infiltrating T cells, synergizing with anti-PD-1 to enhance anti-tumor efficacy. An in-depth study of the biological mechanisms of oxidized sterols will not only enhance our understanding of the complexity of the tumor immune microenvironment but may also reveal new therapeutic targets, providing innovative strategies for tumor immunotherapy.