PMID- 32404543 OWN - NLM STAT- MEDLINE DCOM- 20210331 LR - 20210331 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 43 IP - 7 DP - 2020 Jul 1 TI - Latifolin Inhibits Oxidative Stress-Induced Senescence via Upregulation of SIRT1 in Human Dermal Fibroblasts. PG - 1104-1110 LID - 10.1248/bpb.b20-00094 [doi] AB - Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (H(2)O(2))-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated beta-galactosidase (SA-beta-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21(Cip1/WAF1), p16(Ink4alpha), pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-beta-gal activity after H(2)O(2) exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects. FAU - Lim, Seok-Hee AU - Lim SH AD - Department of Biochemistry, Wonkwang University School of Medicine. FAU - Li, Bing Si AU - Li BS AD - Department of Biochemistry, Wonkwang University School of Medicine. FAU - Zhu, Ri Zhe AU - Zhu RZ AD - Department of Biochemistry, Wonkwang University School of Medicine. FAU - Seo, Jae-Ho AU - Seo JH AD - Department of Biochemistry, Wonkwang University School of Medicine. FAU - Choi, Byung-Min AU - Choi BM AD - Department of Biochemistry, Wonkwang University School of Medicine. LA - eng PT - Journal Article DEP - 20200512 PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Phenols) RN - 0 (latifolin) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Cells, Cultured MH - Cellular Senescence/*drug effects/physiology MH - Dose-Response Relationship, Drug MH - Fibroblasts/*drug effects/metabolism MH - Humans MH - Hydrogen Peroxide/toxicity MH - Oxidative Stress/*drug effects/physiology MH - Phenols/*pharmacology MH - Sirtuin 1/*biosynthesis MH - Skin/cytology/drug effects/metabolism MH - Up-Regulation/*drug effects/physiology OTO - NOTNLM OT - human dermal fibroblast OT - latifolin OT - mammalian target of rapamycin OT - oxidative stress OT - senescence OT - silent information regulator 1 EDAT- 2020/05/15 06:00 MHDA- 2021/04/01 06:00 CRDT- 2020/05/15 06:00 PHST- 2020/05/15 06:00 [pubmed] PHST- 2021/04/01 06:00 [medline] PHST- 2020/05/15 06:00 [entrez] AID - 10.1248/bpb.b20-00094 [doi] PST - ppublish SO - Biol Pharm Bull. 2020 Jul 1;43(7):1104-1110. doi: 10.1248/bpb.b20-00094. Epub 2020 May 12.