Celastrol as a promising botanical antifungal agent against sorghum anthracnose: efficacy and synergistic potential

Abstract BACKGROUND Sorghum is an essential staple crop across the globe, but its productivity is persistently threatened by Colletotrichum sublineola , the causal agent of sorghum anthracnose. This destructive fungal disease severely impairs yield stability and seed quality. Despite ongoing research efforts, considerable gaps remain in the exploration of natural product resources for the development of dedicated botanical fungicides targeting sorghum anthracnose. RESULTS In order to address this research gap, we adopted a natural product repurposing strategy to systematically screen 60 commercially available natural products and evaluate their in vitro antifungal efficacy against C. sublineola . Here, we report for the first time that celastrol exhibits potent in vitro inhibition of C. sublineola , with a median effective concentration (EC 50 ) value of 1.24 μg mL –1 . In vivo assays confirmed that celastrol exhibited prominent curative and protective effects against sorghum anthracnose. Mechanistic analyses revealed that celastrol induces excessive intracellular reactive oxygen species accumulation, reduces mitochondrial membrane potential, and depletes cellular ATP content. These physiological perturbations disrupt fungal plasma membrane integrity and ultimately inhibit fungal proliferation. Furthermore, celastrol exhibited no obvious effects on seed germination at 200 μg mL –1 . Additionally, combination treatment with rationally optimized ratios of celastrol and azoxystrobin also produced significant synergistic antifungal activity. CONCLUSIONS Collectively, our results demonstrate the robust antifungal activity of celastrol against C. sublineola , highlighting its potential for development as both a standalone botanical antifungal agent and a key synergistic component in fungicide mixtures. Our findings provide a promising candidate for the sustainable management of sorghum anthracnose. © 2026 Society of Chemical Industry.