[Construction of Polygonati Rhizoma polysaccharide nanoparticles and its protection on mice with Escherichia coli induced sepsis].

Based on the high mortality rate and the limitations of current therapeutic strategies for sepsis, a critical illness, this study innovatively explored the potential application value of nano-formulations based on Polygonati Rhizoma polysaccharides in sepsis prevention. Initially, crude polysaccharides were extracted from the Polygonati Rhizoma by using the conventional water extraction and ethanol precipitation method, followed by a qualitative analysis for their main saccharide components via high-performance liquid chromatography, thereby determining their polysaccharide structures. Subsequently, Polygonati Rhizoma polysaccharides nanoparticles(PSPs NPs) were successfully fabricated through a combination of controlled caramelization reaction and low-temperature grinding technology. The resulting nanoparticles exhibited uniform particle sizes, good dispersibility, and excellent stability, with an average particle size of approximately 150 nm. The morphology, particle sizes, and surface properties of the nanoparticles were systematically characterized by dynamic light scattering and transmission electron microscopy. In vitro study results demonstrate that Cy3 labeled PSPs NPs were efficiently endocytosed by RAW264.7 macrophages, with a significantly higher uptake efficiency than the free polysaccharides. Moreover, the CCK-8 assay demonstrates that PSPs NPs significantly enhance the viability of human monocytic THP-1 cells in a dose-dependent manner, indicating that nano-formulation effectively enhances the bioactivity and immunomodulatory potential of PSPs. In vivo, a mouse model of sepsis induced by intraperitoneal infection of Escherichia coli was established. The results show that prophylactic administration of PSPs NPs significantly improves the 48 h survival rates of mice, attenuates sepsis-associated body weight loss, and exerts significant protective effects against inflammatory infiltration and tissue damage in critical organs including the lung, liver, and kidney, as evidenced by HE staining. Collectively, this study not only establishes a safe and effective nano-delivery system for TCM polysaccharides but also verifies its multi-target and multi-organ protective effects in the early intervention of sepsis by enhancing innate immune responses and regulating the inflammatory reaction pathways. These findings provide a robust theoretical basis and practical pathway for the modern formulation development of active components from TCM and the development of prevention and treatment strategies for sepsis.