Polysaccharides from Polygonatum kingianum Collett & Hemsl ameliorated fatigue by regulating NRF2/HO-1/NQO1 and AMPK/PGC-1α/TFAM signaling pathways, and gut microbiota

Int J Biol Macromol. 2024 May;266(Pt 2):131440. doi: 10.1016/j.ijbiomac.2024.131440. Epub 2024 Apr 7.

Abstract

Polygonatum kingianum Coll & Hemsl is an important Chinese medicine used for enhancing physical function and anti-fatigue, and polysaccharides (PKPs) are considered as the main bioactive components. However, the mechanisms through which PKPs exert their anti-fatigue effects are not fully understood. This study aimed more comprehensively to explore the anti-fatigue mechanisms of PKPs, focusing on metabolism, protein expression, and gut flora, by using exhaustive swimming experiments in mice. Results showed a significant increase in the exhaustive swimming time of the mice treated with PKPs, especially in the high-dose group (200 mg/kg/day). Further studies showed that PKPs remarkably improves several fatigue-related physiological indices. Additionally, 16S rRNA sequence analysis showed that PKPs increased antioxidant bacteria (e.g., g_norank_f_Muribaculaceae) and the production of short-chain fatty acids (SCFAs), while reducing the abundance of harmful bacteria (e.g., g_Escherichia-Shigella and g_Helicobacter). PKPs also mitigated oxidative stress through activating the NRF2/HO-1 signaling pathway, and promoted energy metabolism by upregulating the expression of AMPK/PGC-1α/TFAM signaling pathway proteins. This research may offer theoretical support for incorporating PKPs as a novel dietary supplement in functional foods targeting anti-fatigue properties.

Keywords: Energy metabolism; Exhaustive swimming time; Oxidative stress; Short chain fatty acids.

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Fatigue* / drug therapy
  • Gastrointestinal Microbiome* / drug effects
  • Heme Oxygenase-1 / metabolism
  • Male
  • Mice
  • NF-E2-Related Factor 2* / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Polygonatum* / chemistry
  • Polysaccharides* / chemistry
  • Polysaccharides* / pharmacology
  • Signal Transduction* / drug effects

Substances

  • AMP-Activated Protein Kinases
  • Heme Oxygenase-1
  • NF-E2-Related Factor 2
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Polysaccharides