title: Methyl caffeate and some plant constituents inhibit age-related inflammation: effects on senescence-associated secretory phenotype (SASP) formation.
abstract: During aging, cells secrete molecules called senescence-associated secretory phenotype (SASP). They constitute chronic low-grade inflammation environment to adjacent cells and tissues. In order to find inhibiting agents of SASP formation, 113 plant constituents were incubated with BJ fibroblasts for 6 days after treatment with bleomycin. Several plant constituents showed considerable inhibition of IL-6 production, a representative SASP marker. These plant constituents included anthraquinones such as aurantio-obtusin, flavonoids including astragalin, iristectorigenin A, iristectorigenin B, linarin, lignans including lariciresinol 9-O-glucoside and eleutheroside E, phenylpropanoids such as caffeic acid and methyl caffeate, steroid (ophiopogonin), and others like centauroside, rhoifolin and scoparone. In particular, methyl caffeate down-regulated SASP factors such as IL-1α, IL-1β, IL-6, IL-8, GM-CSF, CXCL1, MCP-2, and MMP-3. Inhibition of these SASP mRNA expression levels also coincided with the reduction of IκBζ expression and NF-κB p65 activation without affecting the expression levels of senescence markers, p21 or pRb. Taken together, the present study demonstrated that methyl caffeate might be a specific and strong inhibitor of SASP production without affecting the aging process. Its action mechanisms involve the reduction of IκBζ expression and NF-κB p65 activation. Therefore, this compound might be effective in alleviating chronic low-grade inflammation linked to age-related degenerative disorders.
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lim
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea.
authors.forename: Byung Kyu
authors.initials: BK
authors.lastname: Park
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea.
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea.
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea. hpkim@kangwon.ac.kr.
authors.forename: Hyun Pyo
authors.identifier: http://orcid.org/0000-0003-3077-4931
authors.initials: HP
authors.lastname: Kim
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D010641:Phenotype; D013329:Structure-Activity Relationship
chemical_list: D002109:Caffeic Acids; C042405:methyl caffeate
keywords: Chronic low-grade inflammation; IκBζ; Methyl caffeate; SASP; Senescence