Background: Although Platycodin D (PLD) is the main active saponin of Platycodon grandiflorum (PG) and responsible for multiple therapeutic benefits, including antioxidant and antiaging, only few direct demonstrations have been reported on the role of PLD in antiaging process. The present investigation was carried out to elucidate the protection of PLD against aging in vitro and associated molecular mechanisms on H2O2-induced premature senescence model in human -fetal lung diploid fibroblasts 2BS cells.
Methods: The cellular morphology, cell cycle, and senescence-associated β-galactosidase activity assays were used for senescence-like phenotypes determination in the oxidant challenged model. The oxygen-free radicals reactive oxygen species (ROS), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) determinations were estimated by enzyme-linked immunosorbent assay assay. The potential of the mitochondria mass and the mitochondrial membrane were used to observe the alteration of mitochondria. Western blot analysis was performed to determine the protein expression.
Results: The results showed that PLD significantly reversed senescence-like phenotypes in the oxidant challenged model, as well as related molecules expression such as p53, p21, and p16. Moreover, PLD treatment significantly decreased the levels of ROS, 4-HNE, and MDA in H2O2-treated 2BS cells. The mechanisms responsible for the antioxidant and antiaging effects of PLD were investigated, we found that mitochondria under PLD conditions show increase membrane potential ratio and stimulate the proliferation of mitochondria mass. In addition, the protein expression of peroxisome proliferator activated receptor gamma coactivator 1α and its downstream targets, that is, nuclear respiratory factor and mitochondrial transcription factor A were also increased in mitochondrial biogenesis.
Conclusion: These results indicated that PLD prevented H2O2-induced premature senescence in vitro by improving mitochondrial biogenesis to attenuate age-dependent endogenous oxidative damage. Key Message: The study revealed the antioxidant and antiaging potential of PLD against H2O2-induced premature senescence.
Keywords: Cellular premature senescence; Mitochondrial biogenesis; Oxidative stress; Platycodin D.
© 2020 S. Karger AG, Basel.