Picroside II-Encapsulated Nanoformulations as Pyroptosis Inhibitor Alleviate Cytokine Storms and Remodel Gut...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Sepsis is a major cause of death, characterized by pyroptosis, cytokine release syndrome, and gut dysbiosis.
• Current treatments for sepsis often target reactive oxygen species (ROS)/NOD-like receptor pyrin domain-containing 3 (NLRP3)/Caspase-1 pathways, but not lipopolysaccharide (LPS)-triggered pyroptosis.
• Gut microbiota disturbances play a critical role in sepsis progression and secondary cytokine storms, yet are often overlooked in treatment assessments.

Purpose of the Study:

• To develop picroside II-encapsulated, palmitic acid-modified nanoformulations as a pyroptosis modulator for sepsis treatment.
• To investigate the nanoformulations' ability to inhibit lipopolysaccharide (LPS)-induced pyroptosis and cytokine release syndrome.
• To assess the impact of the nanoformulations on gut microbiota composition and intestinal barrier function.

Main Methods:

• Preparation of picroside II-encapsulated, palmitic acid-modified nanoformulations.
• Evaluation of nanoparticle cellular uptake via Toll-like receptor-mediated recognition.
• Assessment of antioxidant, anti-inflammatory, and anti-pyroptosis activities in vitro and in vivo.
• Analysis of pyroptosis-related protein levels and inflammatory factors.
• Investigation of changes in intestinal flora composition and intestinal barrier function.

Main Results:

• Palmitic acid modification enhanced nanoparticle cellular uptake through Toll-like receptor recognition.
• Sustained release of picroside II effectively scavenged reactive oxygen species (ROS), reduced inflammatory factors, and downregulated pyroptosis proteins.
• The nanoformulations demonstrated superior antioxidant, anti-inflammatory, and anti-pyroptosis activities compared to control groups.
• Treatment alleviated LPS-induced multiorgan damage, particularly in the kidney and colon.
• The nanoformulations improved intestinal flora abundance, enhanced intestinal barrier function, and boosted the immune system.

Conclusions:

• Palmitic acid-anchored, picroside II-encapsulated nanoformulations represent a novel strategy for sepsis treatment.
• These nanoformulations effectively inhibit LPS-triggered pyroptosis, reduce systemic inflammation, and mitigate organ damage.
• The treatment also positively modulates gut microbiota, contributing to overall therapeutic efficacy and improved immune homeostasis.