Methyl caffeate and some plant constituents inhibit age-related inflammation: effects on senescence-associated secretory phenotype (SASP) formation

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.

Chronic low-grade inflammation; IκBζ; Methyl caffeate; SASP; Senescence.