Effect of cornuside on experimental sepsis

Area of Science:

• Pharmacology
• Immunology
• Natural Products Chemistry

Background:

• Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
• Current sepsis treatments have limitations, necessitating the development of novel therapeutic agents.
• Secoiridoid glucosides, like cornuside, are plant-derived compounds with potential anti-inflammatory properties.

Purpose of the Study:

• To investigate the antisepsis efficacy of cornuside in vitro using cultured macrophages.
• To evaluate the therapeutic effect of cornuside in an established rat model of sepsis induced by cecal ligation and puncture (CLP).

Main Methods:

• Cornuside was tested on activated macrophages at various concentrations.
• Rats underwent CLP surgery and were randomized to receive intravenous cornuside, imipenem, or a combination.
• Key inflammatory mediators (TNF-alpha, IL-6, IL-10, NO), endotoxin, bacterial counts, and myeloperoxidase levels were measured.

Main Results:

• Cornuside dose-dependently reduced TNF-alpha, IL-6, and nitric oxide (NO) production in macrophages, while increasing IL-10.
• Treatment with cornuside, imipenem, or combination therapy reduced mortality in CLP-induced sepsis in rats.
• Cornuside administration led to decreased systemic levels of TNF-alpha, IL-6, triggering receptor expressed on myeloid cells (TREM), and endotoxin, alongside increased IL-10.
• Reduced bacterial loads and myeloperoxidase activity were observed in various organs following cornuside treatment.

Conclusions:

• Cornuside exhibits significant antisepsis effects by modulating inflammatory responses and reducing bacterial burden.
• The therapeutic action of cornuside in sepsis is attributed to the downregulation of key pro-inflammatory mediators.
• This study provides the first evidence supporting the clinical use of cornuside as a novel immunomodulatory agent for sepsis treatment.