Artesunate: A natural product-based immunomodulator involved in human complement.

Area of Science:

• Immunology
• Pharmacology
• Autoimmune Diseases

Background:

• The complement system is a crucial innate immune defense mechanism.
• Dysregulation of complement is linked to the pathogenesis of various autoimmune diseases.
• Artesunate (ART), an anti-malarial drug, shows potential in treating complement-related autoimmune conditions, but its mechanisms are unclear.

Purpose of the Study:

• To investigate the anti-complement activities of Artesunate (ART).
• To elucidate the mechanisms by which ART affects complement activation pathways.
• To explore the therapeutic potential of ART in complement-mediated autoimmune diseases.

Main Methods:

• Complement-mediated hemolytic assays and cell-based assays using dying Jurkat cells to assess complement interception.
• Development of a selective ELISA system to analyze complement activation via classical, lectin, and alternative pathways.
• Flow cytometry analysis (FACS) using ART-conjugated mesoporous silica particles to identify ART's binding targets.

Main Results:

• ART demonstrated dose-dependent inhibition of C4 and C3 activation, and terminal complement complex assembly across all tested pathways.
• ART primarily blocked C1q, C3, and C5, with a lesser effect on properdin.
• ART's interaction with C1q was localized to its globular head region, and FACS analysis confirmed specific binding to C1q, C3, and C5.

Conclusions:

• This study provides the first evidence of Artesunate's anti-complement bioactivities.
• ART inhibits complement activation through multiple pathways by targeting key complement components like C1q, C3, and C5.
• ART holds potential as a therapeutic agent for complement-related human autoimmune diseases.