title: Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate.
abstract: Ferulate (4-hydroxy-3-methoxycinnamic acid) is a well-known phenolic compound that scavenges free radicals and exerts anti-inflammatory effects. Forkhead box O3a (FOXO3a), a transcription factor that plays important roles in aging processes, decreases with age and is negatively regulated through phosphorylation by phosphatidylinositol 3-kinase (PI3K)/Akt signaling. The present study investigated the efficacy of short-term ferulate feeding on age-related changes in PI3K/Akt/FOXO3a and upstream insulin signaling pathways in aged rats. In addition, changes in manganese superoxide dismutase (MnSOD) and catalase expression were examined because of their dependence on PI3K/Akt/FOXO3a activity. Short-term feeding experiments were done with a diet containing ferulate that was given to aged rats at doses of 3 or 6 mg kg(-1) day(-1) for 10 days. Results showed that FOXO3a activity was increased in the ferulate-fed old group compared with the control old group. Also, ferulate suppressed the PI3K/Akt signaling pathway that is responsible for FOXO3a inhibition in aged rats. Plasma insulin levels and the upstream insulin signaling pathway were also modulated by ferulate correspondingly with PI3K/Akt/FOXO3a activity. The age-related decrease in two major antioxidant enzymes, MnSOD and catalase, was blunted by ferulate, which was accompanied by FOXO3a transcriptional activity. The significance of the present study is the finding that short-term feeding of ferulate effectively modulates age-related renal FOXO3a, PI3K/Akt and insulin signaling pathways, and MnSOD and catalase expression, all of which may be beneficial for attenuating the aging process.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Pusan National University, JangJeon-dong, GeumJeong-gu, Busan, South Korea.
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Jee H
authors.initials: JH
authors.lastname: Jung
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging; D000818:Animals; D001288:Attention / Q000502:physiology*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D015153:Blotting, Western; D003373:Coumaric Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004586:Electrophoresis; D005500:Follow-Up Studies; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010944:Plants; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D003373:Coumaric Acids; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D016166:Free Radical Scavengers; C004999:ferulic acid; D058539:Phosphatidylinositol 3-Kinase