Chicoric acid is an antioxidant molecule that stimulates AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans.
Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5-100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases.
INRA, UMR 866-Dynamique Musculaire et Métabolisme, Montpellier, France ; CNRS, UMR 5247-Institut des Biomolécules Max Mousseron (IBMM), Montpellier, France ; Université Montpellier 1 et 2, Montpellier, France.
Audrey
A
Schlernitzauer
Catherine
C
Oiry
Raphael
R
Hamad
Simon
S
Galas
Fabienne
F
Cortade
Béatrice
B
Chabi
François
F
Casas
Laurence
L
Pessemesse
Gilles
G
Fouret
Christine
C
Feillet-Coudray
Gérard
G
Cros
Gérard
G
Cabello
Richard
R
Magous
Chantal
C
Wrutniak-Cabello
D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics; D002109:Caffeic Acids / Q000494:pharmacology*; D002950:Citrate (si)-Synthase / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D013386:Succinates / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D002109:Caffeic Acids; D013386:Succinates; D014157:Transcription Factors; D010088:Oxidoreductases; D002950:Citrate (si)-Synthase; D000263:Adenylate Kinase; C100435:chicoric acid