An Eudesman Derivative from Verbesina persicifolia D.C. as a Natural Mild Uncoupler in Liver Mitochondria. A New Potential Anti-obesity Agent?

Lisa   Dalla   Via; Aida   N.   Garcia-Argaez; Alessandra      Braga; Mariano      Martinez-Vazquez; Silvia      Grancara; Pamela      Martinis; Enzo      Agostinelli; Antonio      Toninello

doi:10.2174/13816128113199990028

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.

Keywords: Biological activity, eudesmane sesquiterpene, mild uncoupling, mitochondria, natural products.

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