Selenium nanoparticles combined with calycosin treated sepsis through synergistic anti-inflammatory and antioxidant effects.

Sepsis is a heterogeneous disease with high morbidity and mortality due to the limited treatment options. Calycosin (CA), one of the main active ingredients of Astragalus, has potential in sepsis treatment, but its therapeutic effect is limited by low blood concentration and poor bioavailability. To address this challenge, we have successfully prepared a BSA@Se-CA nanocomposite system (BSC) by loading calycosin (CA) onto BSA@Se nanoparticles (BS) through self-assembly. Compared to CA, BSC more effectively scavenges ROS by enhancing the activity of glutathione peroxidase (GPX). Notably, BSC reduces the expression levels of inflammatory factors (NO, IL-6, IL-1β, and TNF-α) in inflammatory macrophages by synergistically inhibiting the NF-κB signaling pathway. Moreover, in vitro experiments demonstrated that BSC can also effectively alleviate RAW264.7 cells and HUVEC cells, helping to maintain normal cellular physiological functions. In vivo, BSC significantly improves the therapeutic effect on sepsis when administered via intraperitoneal injection, increasing the survival rate of septic mice and reducing organ damage. Thus, this study provides a new strategy for enhancing the therapeutic efficiency of natural products with poor bioavailability and offers a potential approach for improving sepsis treatment.