Healthy lifespan extension mediated by oenothein B isolated from Eucalyptus grandis × Eucalyptus urophylla GL9 in Caenorhabditis elegans.

Oenothein B (OEB) exhibits extensive biological activities, but few investigations have been carried out on the pharmacologic influence of OEB on longevity in any organism. To explore the potential pharmacological ability of OEB to postpone the progression of age-related degenerative processes and diseases, we monitored the effects of OEB isolated from Eucalyptus leaves on the lifespan of Caenorhabditis elegans (C. elegans) at four different concentrations. We found that OEB increased the median lifespan of worms by up to 22% in a dose-dependent manner. Further studies demonstrated that OEB significantly enhanced youthfulness (healthy lifespan) by increasing the whole adult life's locomotory mobility, reducing age pigment and reactive oxygen species (ROS) accumulation, and enhancing thermal stress resistance. Furthermore, the genes daf-16, age-1, eat-2, sir-2.1, and isp-1 were required for the healthy longevity benefits induced by OEB, but not the genes mev-1 and clk-1. Taken together, OEB might modulate multiple genetic pathways involved in insulin/IGF-1 signaling (IIS) via age-1 and daf-16, the dietary restriction (DR) pathway via eat-2 and sir-2.1, and the mitochondrial electron transport chain via isp-1 to promote healthy lifespan including the reduction of age pigment and ROS accumulation and the enhancement of locomotory mobility, thermal stress tolerance and lifespan. These findings indicated that OEB has the potential to be developed into the next generation of multi-target drugs for prolonging healthy lifespan and intervening in age-related diseases.