Abstract

The accumulation of oxidative damage and mitochondrial dysfunction is an important factor that contributes to aging. The Psoralea corylifolia seeds (PCS), commonly known as “Boh-Gol-Zhee” in Korea, have been used traditionally as a medicinal remedy. We investigated whether an extract of PCS has protective effects on oxidative stress and mitochondrial function in hepatocytes. The PCS extract showed an antisenescence effect on human diploid fibroblasts as evidenced by a decreased expression of p16INK4a mRNA and senescence-associated β-galactosidase staining. PCS extract treatment reduced H2O2-induced reactive oxygen species (ROS) production in HepG2 cells, inhibited ROS production in hepatocytes of aged mice, and increased superoxide dismutase activity. In H2O2-treated HepG2 cells, PCS extract treatment recovered ATP production. PCS extract treatment recovered the oxygen consumption rate and inhibited reduction of mitochondrial membrane potential induced by oxidative stress, suggesting improvement of mitochondrial function. In addition, PCS extract treatment recovered peroxisome proliferator-activated receptor γ coactivator 1α and carnitine palmitoyltransferase 1 mRNA and protein expression, and inhibited mitochondrial genome damage. Treatment with the major component of PCS extract, bakuchiol, also recovered mitochondrial dysfunction. On the basis of these results, we conclude that PCS extract inhibits ROS production and mitochondrial dysfunction induced by oxidative stress in hepatocytes.

Highlights

  • Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and a biological system’s ability to readily detoxify the reactive intermediates or repair the resulting damage [1]

  • We examined whether Psoralea corylifolia seeds (PCS) extract has an antioxidant effect and improves mitochondrial function in hepatocytes, as hepatocytes are exposed to large amounts of ROS due to their numerous mitochondria and high respiratory rate

  • To examine the effects of PCS extract in senescent cells, “Old” Human diploid fibroblasts (HDF) cells were treated with PCS extract (50 μg/mL) for 24 h, and p16INK4a mRNA expression was analyzed by Quantitative Real-Time RT-PCR (qRT-PCR)

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Summary

Introduction

Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and a biological system’s ability to readily detoxify the reactive intermediates or repair the resulting damage [1]. Disorders in the normal redox state of cells can cause toxic effects through the production of ROS, which include free radicals and peroxides [2]. Oxidative stress is involved in many diseases and may exacerbate their symptoms [3]. The free-radical theory of aging suggests that many agerelated pathologies result from damage to macromolecules by ROS [5, 6]. Mitochondria are the major source and target of ROS [7]. Antioxidant therapy and functional recovery of mitochondria may serve as a treatment approach for inhibiting oxidative stress and aging-associated diseases

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