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

Lihong Song, Tongqi Ge, Zeqin Li, Jinfeng Sun, Gao Li, Yi Sun, Liang Fang*, Ying Jie Ma, Peter Garred

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Complement is an important innate immune defence machinery. Once dysregulated, it is often linked to pathogenesis of diverse autoimmune diseases. Artesunate (ART) is a well-known anti-malarial compound. Recently, ART has been highlighted by its potential therapeutic effects on certain complement-related autoimmune diseases. However, the underlying mechanisms are hitherto unknown. In the present study, we found that ART mediated complement interception as validated by analysis of complement haemolytic assay. In cell-based setup using dying Jurkat cells, ART-mediated complement interception was also confirmed. Further, we newly established an ELISA system selectively allowing complement activation via the classical pathway, the lectin pathway and the alternative pathway, respectively. ELISA analysis revealed that ART dose-dependently inhibited C4 activation, C3 activation and terminal complement complex assembly via the effector pathways. ART was found to blockade C1q, C3 and C5 with a lesser extent to properdin. The interaction of ART with C1q was determined to be mediated via C1q globular head region. FACS analysis using ART-conjugated mesoporous silica particles revealed that ART specifically bound the key therapeutic targets of C1q, C3 and C5 on microparticles. In conclusion, we for the first time report the anti-complement bioactivities of ART and suggest a potential therapeutic benefit of ART in the complement-related human diseases.

Original languageEnglish
Article number111234
JournalBiomedicine and Pharmacotherapy
Volume136
Number of pages11
ISSN0753-3322
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
This work was supported by grants from the Kirsten og Freddy Johansens Fond , the Danish Ministry of Higher Education and Science [Ref. no.: 9096-00027B] and the Danish Research Foundation of Independent Research [ DFF-6110-00489 ].

Keywords

  • Anti-complement activity
  • Artesunate
  • Complement assay
  • Complement regulation
  • Mesoporous silica particles

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