Eriodictyol curbs cardiac fibrosis in mice by engaging ASK1
- In a transverse aortic constriction mouse model and TGF-β–stimulated cardiac fibroblasts, the flavonoid eriodictyol improved cardiac function and reduced fibrosis, oxidative stress and inflammation.
- It bound ASK1 at lysine 398 and altered the kinase's ubiquitination and phosphorylation-driven activation.
- Cardiac-fibroblast-specific ASK1 overexpression and knockout, plus a selective ASK1 inhibitor, were used to test whether the effect depends on ASK1.
💡 Points Based on the abstract
Fibroblast-specific genetics plus an ASK1 inhibitor make the target argument stronger than most natural-product papers manage. Still, a flavonoid is a classic polypharmacology, poor-exposure scaffold. Before calling ASK1 the mechanism I'd want free plasma exposure at the efficacious dose and a K398 mutant that abolishes the effect. ASK1 inhibitors have also had a mixed clinical record.