Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota

Pharmacol Res. 2021 Aug:170:105697. doi: 10.1016/j.phrs.2021.105697. Epub 2021 May 29.

Abstract

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

Keywords: Aging; C. elegans; Complement system; Gut microbiota; Neurodegenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Age Factors
  • Aging / drug effects*
  • Aging / genetics
  • Aging / immunology
  • Aging / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Cell Line, Tumor
  • Complement C3 / metabolism*
  • Down-Regulation
  • Gastrointestinal Microbiome / drug effects*
  • Longevity / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Neuroinflammatory Diseases / genetics
  • Neuroinflammatory Diseases / immunology
  • Neuroinflammatory Diseases / metabolism
  • Neuroinflammatory Diseases / prevention & control
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Polygala* / chemistry
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Spatial Memory / drug effects
  • Transcriptome

Substances

  • C3 protein, mouse
  • Complement C3
  • Neuroprotective Agents
  • Plant Extracts
  • Saponins