AI-driven pipeline discovers ombuin as a novel M1 macrophage polarization inhibitor for sepsis treatment - PubMed
5 hours ago
- #AI-driven drug discovery
- #sepsis treatment
- #macrophage polarization
- AI-driven pipeline identifies ombuin as a novel M1 macrophage polarization inhibitor for sepsis treatment.
- Sepsis involves dysregulated immune responses with excessive M1 macrophage polarization, leading to cytokine storms.
- Traditional drug discovery is costly and time-consuming, prompting the use of AI for screening.
- A transformer-variational autoencoder (TVAE) integrated molecular fingerprints to screen 5516 natural products.
- Ombuin showed potent suppression of LPS-induced M1 polarization and pro-inflammatory cytokines (IL-6, TNF-α) in vitro.
- In a mouse sepsis model, ombuin improved survival and reduced systemic inflammation by balancing M1/M2 polarization.
- Ombuin binds to and activates ALDH2, inhibiting NF-κB p65 nuclear translocation, a key driver of M1 polarization.
- The study highlights AI's role in efficiently discovering immunomodulatory agents like ombuin for sepsis therapy.