Bufalin Inhibits Cytokine Storm by Regulating TLR4/TLR3 Signaling Pathway

TL;DR

Bufalin, a compound from toad venom, reduces inflammation by inhibiting key immune signaling pathways, offering potential as a new anti-inflammatory drug.

Contribution

The study identifies bufalin's anti-inflammatory mechanism through TLR4/TLR3 signaling inhibition and suggests its potential as a drug candidate.

Findings

Bufalin reduces pro-inflammatory cytokines like IL-6 and TNF-α by inhibiting IKBα and IRF3 phosphorylation.

Molecular docking suggests bufalin targets MD-2 coupled with TLR4 activated by lipopolysaccharide.

The findings validate traditional Chinese medicine's use of toad venom for inflammatory diseases.

Abstract

Bufalin is one main component of the dried venom from Bufo gargarizans Cantor, which has anti‐tumor, cardiotonic, anti‐inflammatory and other physiological activities. However, in recent years, researchers have mainly paid attention to its anti‐tumor effect and neglected its anti‐inflammatory effect.

We used lipopolysaccharide (TLR4 ligand) and poly inosinic acid (TLR3 ligand) to stimulate cultured macrophages to induce inflammatory condition. Transcriptome sequencing and molecular experiments were performed to investigate the underlying mechanism.

Bufalin could significantly reduce the production of pro‐inflammatory factors (IL‐6, TNF‐α, IL‐1β, IL‐8, CXCL10, etc.), through inhibiting the phosphorylation of IKBα and IRF3, and thus down‐regulating Toll‐like receptor pathway. Molecular docking predicted that one of the molecular targets of bufalin is MD‐2 coupled with lipopolysaccharide‐activated TLR4.

These findings not only support the pharmacological basis of using toad to treat inflammatory diseases in the Chinese medical history, but also provide a promising anti‐inflammatory drug candidate for future clinical application.

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