Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans

• Published in: PloS one 2011-12, Vol.6 (12), p.e28835-e28835
• Main Authors: Cai, Wai-Jiao, Huang, Jian-Hua, Zhang, Su-Qin, Wu, Bin, Kapahi, Pankaj, Zhang, Xin-Min, Shen, Zi-Yin
• Format: Article
• Language: English
• Subjects: Age; Aging; Aging (natural); Animals; Biological activity; Biology; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Chemistry; Chinese medicine; Derivatives; Drosophila; Drug dosages; Epimedium; Flavonoids; Flavonoids - pharmacology; Gene expression; Genetics; Heat shock; Heat shock factors; Heat shock proteins; High performance liquid chromatography; Hospitals; Insects; Insulin; Insulin - metabolism; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Life span; Liquid chromatography; Localization; Locomotion; Longevity; Mammals; Medicine; Mutation; Nematodes; Oxidative stress; Paralysis; Plant extracts; Polyglutamine; Signaling; Transcription factors; Worms
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0028835

Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.