Beneficial effects of sappanone A on lifespan and thermotolerance in Caenorhabditis elegans

Sappanone A (SA) is a homoisoflavonoid compound isolated from Caesalpinia sappan L. that selectively binds to inosine monophosphate dehydrogenase 2, a protein involved in aging. It is unknown if SA has an anti-aging effect and what is it mechanism. This study aimed to investigate the lifespan-extending and health-enhancing effects of SA, and the potential pharmacological mechanism in Caenorhabditis elegans (C. elegans). The worms were exposed to 0-50 mu M SA. The effect on the lifespan was observed, and health status was evaluated by detecting motility, feeding, reproduction, thermotolerance, lipofuscin and ROS accumulation. To explore a possible mechanism, the transcription of the genes of the insulin/insulin-like growth factor-1 signalling pathway and heat stress response was detected by RT-qPCR. Moreover, subcellular distribution of green fluorescent protein-labeled DAF-16 was determined, and the interaction between SA and HSP-90 protein was simulated by molecular docking. We found that SA prolonged lifespan in C. elegans and enhanced motility and thermotolerance. The feeding and reproduction were not impacted. The ROS and lipofuscin accumulation was declined. Mechanistic study revealed that the gene expression levels of daf-16 and hsp-90 were up-regulated. Moreover, DAF-16 was translocated into the nucleus. SA was docked into the active pocket of HSP-90 in the simulation. SA (50 mu M) can extend lifespan in C. elegans and decelerate aging by regulating the IIS pathway, and daf-16 is specifically important for the regulation of longevity. HSP-90 was involved in the enhancement of thermotolerance. Thus, SA may act as a promising candidate for the development of an anti-aging agent.