<i>Piper betle</i> L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts

Abstract

<i>Piper betle</i> (PB) is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs) was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%), presenescent (127.3%), and senescent (157.3%) HDFs. Increased expressions of <i>PRDX6</i>, <i>TP53</i>, <i>CDKN2A</i>, <i>PAK2</i>, and <i>MAPK14</i> were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of <i>SOD1</i> increased, whereas <i>GPX1</i>, <i>PRDX6</i>, <i>TP53</i>, <i>CDKN2A</i>, <i>PAK2</i>, and <i>MAPK14</i> were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.