Elucidating new triterpenoid saponins from the roots of Panax quinquefolium L.: A phytochemical advancement for neurodegenerative therapeutics

Bioorg Chem. 2026 Mar:170:109459. doi: 10.1016/j.bioorg.2025.109459. Epub 2025 Dec 29.

Abstract

Oxidative stress is considered a significant modulator of various neurodegenerative diseases. Elevated levels of excess active substances, such as reactive oxygen species (ROS), can result in redox imbalances within organisms. Consequently, antioxidant strategies have been proposed as potential preventive and therapeutic measures for neurodegenerative diseases. It is essential to discover effective antioxidants and neuroprotective bioactive compounds. Panax quinquefolium L. has served as an important functional food, functioning both as a component in health supplements and as a medicinal herb. In pursuit of a more comprehensive understanding of the neuroprotective activity of Panax quinquefolium L. on neuronal cells, a phytochemical investigation was undertaken. This investigation reported the first isolation and characterization of fourteen previously undocumented triterpenoid-type saponins (1-14) as well as nine previously identified triterpenoid saponins (15-23). The structures of the compounds (1-14) were validated through comprehensive spectroscopic analyses, complemented by quantum chemical calculations of 13C NMR data, as well as a comparison between the experimental and calculated Electron Capture Detector (ECD) data. These compounds mitigated neuronal damage induced by hydrogen peroxide (H2O2) by significantly enhancing the viability of PC12 cells and reducing levels of oxidative stress. Among the compounds examined, 1, 2, and 3 demonstrated particularly pronounced antioxidant effects, with compound 1 exhibiting the highest antioxidant capacity. Treatment with 1 significantly decreased the levels of ROS and influenced the expression of oxidative defense proteins in PC12 cells, specifically resulting in a decrease in Keap1 levels and an increase in the expression of Nrf2, HO-1, and NQO1 proteins. Furthermore, 1 inhibited H2O2-induced apoptosis in PC12 cells, attenuated mitochondrial depolarization, and reduced the Bax/Bcl-2 ratio. In conclusion, the results suggest that compound 1 exerts neuroprotective effects through antioxidant and apoptotic pathways.

Keywords: Neuroprotective effect; Oxidative stress; Panax quinquefolium L.; Triterpenoid saponins.

MeSH terms

  • Animals
  • Antioxidants* / chemistry
  • Antioxidants* / isolation & purification
  • Antioxidants* / pharmacology
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Molecular Structure
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / isolation & purification
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Panax* / chemistry
  • Phytochemicals* / chemistry
  • Phytochemicals* / isolation & purification
  • Phytochemicals* / pharmacology
  • Plant Roots* / chemistry
  • Rats
  • Reactive Oxygen Species / metabolism
  • Saponins* / chemistry
  • Saponins* / isolation & purification
  • Saponins* / pharmacology
  • Structure-Activity Relationship
  • Triterpenes* / chemistry
  • Triterpenes* / isolation & purification
  • Triterpenes* / pharmacology

Substances

  • Saponins
  • Triterpenes
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Antioxidants
  • Hydrogen Peroxide
  • Phytochemicals