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

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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.

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Acknowledgement

The plant constituents used in this study were provided from the Research Center for Standardization of Herbal Medicines (Seoul, Korea) (2005–2014). We acknowledge Profs. Kun Ho Son (Andong Nat’l. Univ.), Sang Kook Lee, Sam Sik Kang, Jin Woong Kim (Seoul Nat’l. Univ.), Jae Soo Choi (Bukyung Univ.), Kang Rho Lee (Sungkyunkwan Univ.), En Kyoung Seo (Ewha Wonmen’ Univ.), Kiwhan Bae, Young Ho Kim (Chungnam Nat’l. Univ.), En Rhan Woo (Chosun Univ.), Dong Woong Lee (Dongkook Univ.) and the graduate students for their original contribution to isolate the constituents from various herbal products. We express our sincere thanks to Prof. Yeong Shik Kim (Seoul National Univ.) for providing ginsenosides. This study was financially supported by the Basic Research Program through the National Research Foundation (NRF-2013R1A1A2005609) and BK21-plus from the Ministry of Education. The bioassay facility of New Drug Development Institute (KNU) was used.

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  1. College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea

    Hyun Lim, Byung Kyu Park, Sook Young Shin, Yong Soo Kwon & Hyun Pyo Kim

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  1. Hyun Lim
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Lim, H., Park, B.K., Shin, S.Y. et al. Methyl caffeate and some plant constituents inhibit age-related inflammation: effects on senescence-associated secretory phenotype (SASP) formation. Arch. Pharm. Res. 40, 524–535 (2017). https://doi.org/10.1007/s12272-017-0909-y

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