Iridis tectori Rhizome Alleviates LPS-Triggered Inflammatory Responses Through Inhibiting NF-κB Signaling in...

Area of Science:

• Pharmacology
• Natural Products Chemistry
• Immunology

Background:

• The rhizome of Iris tectorum Maxim., known as Chuan She Gan (CSG), is traditionally used for inflammation-related conditions.
• CSG is often used as a substitute for She Gan in certain regions.
• Evaluating the anti-inflammatory potential and molecular mechanisms of CSG is crucial for validating its traditional applications.

Purpose of the Study:

• To assess the anti-inflammatory activity of the ethanolic extract of Chuan She Gan (CSG).
• To elucidate the molecular mechanisms underlying CSG's anti-inflammatory effects.
• To investigate CSG's impact on inflammatory mediators in both cellular and animal models.

Main Methods:

• Preparation and HPLC analysis of CSG to identify key constituents (isoflavones/glycosides).
• Assessment of anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, measuring nitric oxide (NO), cytokines (IL-6, MCP-1), and gene expression.
• Investigation of signaling pathways (NF-κB, AP-1/MAPK) using reporter assays and Western blotting, and evaluation in endotoxemic mouse models.

Main Results:

• CSG contains characteristic isoflavones/glycosides: tectoridin, iridin, tectorigenin, and irigenin.
• CSG dose-dependently inhibited NO production, iNOS expression, and reduced IL-6, MCP-1, and pro-IL-1β in LPS-stimulated macrophages.
• CSG suppressed NF-κB activation by inhibiting IκBα phosphorylation and p65 nuclear translocation, with minimal effect on AP-1/MAPK signaling. In mice, CSG reduced serum IL-6, MCP-1, and TNF-α.

Conclusions:

• CSG demonstrates significant anti-inflammatory activity in both cellular and animal models.
• The anti-inflammatory effects in macrophages are primarily mediated by the inhibition of the NF-κB signaling pathway.
• CSG effectively reduces pro-inflammatory cytokine levels in endotoxemic mice, supporting its traditional therapeutic use.