The Phytochemical Glaucarubinone Promotes Mitochondrial Metabolism, Reduces Body Fat, and Extends Lifespan ofCaenorhabditis elegans

Abstract

Naturally occurring compounds that promote energy expenditure and delay aging in model organisms may be of significant interest, since these substances potentially provide pharmaceutical approaches to tackle obesity and promote healthy lifespan in humans. We aimed to test whether pharmaceutical concentrations of glaucarubinone, a cytotoxic and antimalarial quassinoid known from different species of the plant family Simaroubaceae, are capable of affecting metabolism and/or extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans roundworms, maintained on agar plates, were fed with E. coli strain OP50 bacteria, and glaucarubinone was applied to the agar to test (i) whether it alters respiration rates and mitochondrial activity, (ii) whether it affects body fat content, and (iii) whether it may promote longevity by quantifying survival in the presence and absence of the compound. We have found that glaucarubinone induces oxygen consumption and reduces body fat content of C. elegans. Moreover and consistent with the concept of mitohormesis, glaucarubinone extends C. elegans lifespan when applied at a concentration of 1 or 10 nanomolar. Taken together, glaucarubinone is capable of reducing body fat and promoting longevity in C. elegans, tentatively suggesting that this compound may promote metabolic health and lifespan in mammals and possibly humans.

Effect of Antioxidants Supplementation on Aging and Longevity

“…Extension of lifespan is abolished by coapplication of an antioxidant, indicating that increased ROS formation is required for the extension of lifespan by lonidamine [98]. The same effects were found in C. elegans for low concentrations of arsenite [99], a cytotoxic and antimalarial quassinoid glaucarubinone [100], and glucose restriction [101]. …”

l-Theanine extends lifespan of adult Caenorhabditis elegans

“…Bristol). All experiments were performed exactly as previously described [1, 7–9] except that streptomycin and 5-fluoro-2′-deoxyuridine were omitted, and synchronization was performed as previously described [7]. E. coli OP50 bacteria were heat-inactivated as previously described [7] for 45 min and used as the only food source.…”

“…A number of such compounds have been identified in recent years, including rapamycin, 2-deoxy- d -glucose, resveratrol, and additional phytochemicals (as summarized in [1]).…”

Natural or Synthetic Anti-Melanogenic Compounds That Block the PDGFR-EGFR-PAK1-MITF-Tyrosinase Signaling Pathway

“…Since melanogenesis also depends on both PAK1 (inducible) and PAK4 (basal), we have tested its anti-melanogenic effect using B16F10 melanoma cells [39], and confirmed that it indeed inhibits the melanogenesis with IC 50 around 440 nM (Be-Tu PT, et al, unpublished observation). Interestingly, in 2011, a group at Jena University in Germany found that this compound extends the lifespan of C. elegans, suggesting that it would not cause any side effect during cancer therapy or cosmetic skin-treatment [40].…”