Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age-Related Diseases by Activating AMPK, DAF-16, and HSF-1

Oxid Med Cell Longev. 2021 Sep 25:2021:7656834. doi: 10.1155/2021/7656834. eCollection 2021.

Abstract

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50 μM of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans (C. elegans) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans. Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans. Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1, isp-1, eat-2, and rsks-1. Trigonelline requires daf-16, hsf-1, and aak-2 to extend the lifespan of C. elegans. Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3, gst-4, hsp-16.1, and hsp-12.6. Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Aging / drug effects*
  • Alkaloids / administration & dosage*
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Disease Models, Animal
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Heat-Shock Response / drug effects
  • Kaplan-Meier Estimate
  • Longevity / drug effects*
  • Neurodegenerative Diseases / prevention & control*
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage*
  • Signal Transduction / drug effects*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Trigonella / chemistry*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Alkaloids
  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Plant Extracts
  • Transcription Factors
  • daf-16 protein, C elegans
  • heat shock factor-1, C elegans
  • trigonelline
  • fenugreek seed meal
  • AMP-Activated Protein Kinases