Material basis, effect, and mechanism of ethanol extract of Pinellia ternata tubers on oxidative stress-induced cell senescence

Phytomedicine. 2020 Oct:77:153275. doi: 10.1016/j.phymed.2020.153275. Epub 2020 Jul 2.

Abstract

Background: The tuber of Pinellia ternata has been used for a thousand years in China. P. ternata possessed the activities of anti-emetic, sedative-hypnotic, anti-cancer, anti-asthmatic, anti-tussive, and anti-inflammatory. It is the representative of expectorant medicines in Traditional Chinese Medicine (TCM). Phlegm is the pathological product and a new pathogenic factor of the metabolite, which is analogous to the damage of oxidative stress.

Purpose: The objectives of the study were to investigate the protective activity and mechanism of ethanol extract of P. ternata tubers (PTE) and its main constituents on oxidative stress-induced cell senescence.

Methods: H2O2 and AAPH were used to establish cellular senescence models. The anti-aging effects of PTE and its components were evaluated by SA-β-gal staining, flow cytometry, scanning electron microscope (SEM), and multiple microplate reader, the molecular mechanisms of them were investigated by qRT-PCR and Western Blot.

Results: We found PTE exhibited the apparent effect on cell senescence, evidenced by inhibiting senescence β-Galactosidase (SA-β-gal) expression, lipofuscin accumulation, cell cycle arrest at the G2/M phase, oxidative damage and apoptosis, and increasing telomerase activity. Their mechanisms were related to increase expressions of SIRT1, forkhead box 3a (Foxo3a), Bcl-2, active regulator of SIRT1, RPS19BP1 (AROS), and Hu antigen R (HuR), but decrease Bax, p53 and deleted in breast cancer 1 (DBC1) levels. Furthermore, adenosine, and succinic acid, as the critical substances in PTE, could also inhibit SA-β-gal expression and cell cycle arrest, down-regulate the expression of Bax, and up-regulate Bcl-2, SirT1, and Foxo3a.

Conclusions: We have demonstrated that PTE slows down oxidative stress-induced cell senescence, and adenosine and succinic acid are the key active components.

Keywords: Oxidative stress; Pinellia ternata; SIRT1; Senescence.

MeSH terms

  • Animals
  • Cellular Senescence / drug effects
  • Chlorocebus aethiops
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / chemistry
  • Ethanol / chemistry
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Lipofuscin / metabolism
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Pinellia / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Tubers / chemistry
  • Protective Agents / chemistry
  • Protective Agents / pharmacology
  • Proteins / genetics
  • Proteins / metabolism
  • Rats
  • Telomerase / metabolism
  • Vero Cells
  • beta-Galactosidase / metabolism

Substances

  • Drugs, Chinese Herbal
  • Lipofuscin
  • Plant Extracts
  • Protective Agents
  • Proteins
  • Ethanol
  • Hydrogen Peroxide
  • Telomerase
  • beta-Galactosidase