@misc{10481/59344,
year = {2019},
month = {12},
url = {http://hdl.handle.net/10481/59344},
abstract = {Lippia citriodora (LC) represents a complex plant-derived source of polyphenols and iridoids
that has shown beneficial properties against obesity-related metabolic disorders. The complete
extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell
and animal models. In this work, we aimed to elucidate the contribution of the different
compounds present in the LC extract on the AMPK activation capacity of the whole extract.
Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray
ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major
compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement
of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity
in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic
acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard
and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between
loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three
compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma
subunit and/or the different sites of the interaction zones between the gamma and beta subunits.
Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside,
the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research
aimed to develop optimized combinations of polyphenols as a new nutritional strategy against
obesity-related metabolic disorders.},
organization = {This work was supported by projects AGL2015-67995-C3-1-R and RTI2018-096724-B-C21 (Spanish
Ministry of Economy and Competitiveness), PROMETEO/2016/006 from Generalitat Valenciana and CIBER
(CB12/03/30038, Fisiopatologia de la Obesidad y la Nutricion, CIBERobn, Instituto de Salud Carlos III). Scholarships
ACIF/2016/230 and APOSTD/2017/023 from Generalitat Valenciana cofinanced with the European Social Fund,
and by a grant from the Federative Research Structure TERSYS from Avignon University, France.},
publisher = {MDPI},
keywords = {Lippia citriodora},
keywords = {Polyphenol},
keywords = {Adipocyte},
keywords = {Molecular docking},
title = {The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders},
doi = {10.3390/nu11122961},
author = {Olivares-Vicente, Mariló and Sánchez Marzo, Noelia and Encinar, José Antonio and Cádiz Gurrea, María de la Luz and Lozano Sánchez, Jesús and Segura Carretero, Antonio and Arráez Román, David and Riva, Catherine and Barrajón-Catalán, Enrique and Herranz-López, María and Micol Molina, Vicente},
}