title: An eudesman derivative from Verbesina persicifolia D.C. as a natural mild uncoupler in liver mitochondria. A new potential anti-obesity agent?
abstract: 4β-cinnamoyloxy,1β,3α-dihydroxyeudesm-7,8-ene (CDE) extracted from Verbesina persicifolia induces bioenergetic collapse in rat liver mitochondria (RLM), monitored as a fall in the respiratory control index and ADP/O values. This fall in energy is accompanied by a protonophore effect and membrane potential (Δψ) collapse, demonstrating that CDE behaves as a typical uncoupling agent. However, when examining the effect of CDE in detail, we found that it acts as a "mild" uncoupler because it drops Δψ and increases respiratory state 4. The proposed mechanism is based on the interaction of CDE with membrane protein cytochrome C oxidase, which is implicated in proton permeability, and with the respiratory chain for the generation of reactive oxygen species which mediate and regulate the activity of the above membrane protein. Considering the energy collapse, "mild" uncoupling, and the fact that CDE is largely used in folk medicines, this extract may be viewed as a potentially effective anti-obesity drug and a natural lead compound for developing new natural uncouplers against obesity.
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Aída N
authors.initials: AN
authors.lastname: García-Argáez
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braga
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
authors.forename: Silvia
authors.initials: S
authors.lastname: Grancara
authors.forename: Pamela
authors.initials: P
authors.lastname: Martinis
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
authors.affiliation: Department of Biomedical Sciences, University of Padova,Viale G. Colombo, 3, 35131 Padova, Italy. antonio.toninello@unipd.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toninello
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D045787:Sesquiterpenes, Eudesmane / Q000302:isolation & purification / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000302:isolation & purification / Q000494:pharmacology; D031208:Verbesina / Q000737:chemistry*
chemical_list: C000592020:4-cinnamoyloxy-1,3-dihydroxyeudesm-7,8-ene; D019440:Anti-Obesity Agents; D017382:Reactive Oxygen Species; D045787:Sesquiterpenes, Eudesmane; D014475:Uncoupling Agents; D003576:Electron Transport Complex IV