Abstract

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

Highlights

  • In the present study, aged rats were fed with Dendranthema zawadskii (DZ) extract at 0.2–1 mg·kg−1 ·day−1 for 7 d to test if DZ extract treatment inhibited the activation of NF-κB, which is supposedly induced by senescence in aortic tissues

  • COX-2 expressions induced by NF-κB translocation (Figure 6). These results suggest that DZ extract effectively inhibited age-related NF-κB activation and inflammation

  • The present study found that doxorubicin-induced senescence in human dermal fibroblast cells (HDFs) was suppressed and that oxidative stress and suppressed cellular senescence as well as agingrelated inflammation was reduced

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chronic production of ROS in aged animals damages cellular components, inducing senescence or senile diseases [2]. Park (DZ) is a perennial dicotyledon that belongs to the order Asterales and family Compositae It is a special plant found on Ulleungdo, an island of Korea, which has been designated as a rare and endangered species by the Korea Forestry Service. Plants that belong to the genus Dendranthema of the Compositae family have been known from ancient times to have excellent medicinal effects, and various plant species of this family have been used as food articles and medicines. No studies have investigated the inhibitory effects of DZ extracts or its isolated components on cellular senescence in cells or aging by using animal models. In this study, DZ extract was investigated for its possible inhibitory effects against doxorubicin-induced aging in skin fibroblasts. The extract was examined for its effects on aging-related changes in inflammatory proteins of the vascular tissue from aged rats

Plant Resource and Extract Preparation
Chemicals
Cell Line and Cell Culture
Cell Viability Assay
Induction of Cellular Senescence by Doxorubicin
Experimental Animals and Treatment
Tissue Preparation and Measurement of Oxidative Stress
Western Blot Analysis of Aorta Tissue
Phenolic Compound Analysis Using a HPLC–UVD
2.10. Statistical
Inhibition
Effects of DZ Extract on Redox
Suppressive Effect of DZ Extract on Age-Induced Nuclear Factor
Discussion
Conclusions

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