title: 3β-Hydroxy-urs-12-en-28-oic acid prolongs lifespan in C. elegans by modulating JNK-1.
abstract: Remarkably the c-Jun-NH2-terminal kinase (JNK) pathway is all evolutionarily conserved across species. In view of the hypothesis that increased stress resistance subdue aging, we investigated the role of ursolic acid (3β-Hydroxy-urs-12-en-28-oic acid; UA) in the pioneering aging model Caenorhabditis elegans with an increase in mean and maximum lifespan by up to 30%. Our genetic study unravelled the underlying pathway where JNK-1 is acting independently of insulin-IGF-1 signalling (IIS) pathway to modulate longevity. In support of in vivo results in silico docking study of UA with C. elegans JNK-1 ATP-binding site suggested promising binding affinity exhibiting binding energy of -8.11 kcalmol-1. UA induced JNK-1 activation in wild-type animals underlie the importance of pharmacological interventions in the delineation of molecular targets for aging and associated pathologies.
authors: Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors: Hema
authors: H
authors: Negi
authors: Department of Metabolic and Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors: Aparna
authors: A
authors: Shukla
authors: Department of Metabolic and Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India. Electronic address: f.khan@cimap.res.in.
authors: Feroz
authors: F
authors: Khan
authors: Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India. Electronic address: r.pandey@cimap.res.in.
authors: Rakesh
authors: R
authors: Pandey
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C000597093:3beta-hydroxy-urs-11-en-13beta,28-olide; D029742:Caenorhabditis elegans Proteins; D014315:Triterpenes; C437322:JNK-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases
keywords: C. elegans; JNK-1; Lifespan; Molecular docking; Ursolic acid