# Multi-omics integration identifies ganoderic acid A as a TNFα inhibitor for treating sepsis-related liver injury

## TL;DR

This study finds that ganoderic acid A, from a type of mushroom, may treat liver injury caused by sepsis by inhibiting a key inflammatory protein.

## Contribution

The study identifies TNFα as a direct target of ganoderic acid A using multi-omics and biophysical methods.

## Key findings

- GAA directly binds to TNFα, as confirmed by SPR and MD simulations.
- GAA inhibits TNFα/NF-κB signaling, reducing macrophage M1 polarization and liver injury.
- The findings provide a mechanistic basis for GAA's hepatoprotective effects in sepsis-related liver injury.

## Abstract

Ganoderic acid A (GAA), a major bioactive triterpenoid from Ganoderma lucidum, is known for its anti-inflammatory effects; however, its precise molecular targets in sepsis-related liver injury (SRLI) remain unclear. Integrating network pharmacology and transcriptomic analysis, we identified Tumor Necrosis Factor-alpha (TNFα) as a primary candidate target. Subsequent biophysical validation using surface plasmon resonance (SPR) and molecular dynamics (MD) simulations confirmed that GAA directly binds to TNFα. Functionally, this interaction inhibits the TNFα/NF-κB signaling axis, thereby suppressing macrophage M1 polarization and ameliorating liver injury in vitro and in vivo. This study identifies TNFα as a primary candidate target of GAA, providing a mechanistic basis for its hepatoprotective effects and therapeutic potential.