Isoparvifuran isolated from Dalbergia odorifera attenuates H2O2-induced senescence of BJ cells through SIRT1 activation and AKT/mTOR pathway inhibition

Abstract

Isoparvifuran is a benzofuran compound isolated from the heartwood of Dalbergia odorifera. Related research reported that isoparvifuran has antioxidant property. However, it is unclear whether isoparvifuran has anti-aging effects. In this research, we established an aging model, hydrogen peroxide (H₂O₂)-induced BJ cell senescence, to explore the protective effect of isoparvifuran on cell senescence and its related mechanisms. Our results revealed that isoparvifuran obviously attenuated H₂O₂-induced cell senescence, increased the cell proliferation rate,and reversed senescence-associated molecular markers expression such as cyclin D1, pRb, caveolin-1, ace-p53, p21 and p16. Moreover, isoparvifuran dose and time dependently increased the expression level of Sirtuin 1 (SIRT1) in BJ cells. The inhibition of SIRT1 obviously reversed the reduction of SA-β-gal activity and the alteration of senescence-associated molecular markers induced by isoparvifuran. Additionally, isoparvifuran also inhibited H₂O₂-induced AKT and S6 phosphorylation and increase of SA-β-gal activity. In summary, isoparvifuran protects BJ cells from H₂O₂-induced premature senescence, the anti-senescence effect of isoparvifuran is associated with the activation of SIRT1 and the suppression of AKT/mTOR signaling pathway.

Keywords: AKT/mTOR signaling pathway; Antioxidant: SIRT1; Cellular senescence; Isoparvifuran.