Inhibition of the NF-κB and mTOR targets by urolithin A attenuates D-galactose-induced aging in mice

Food Funct. 2023 Nov 27;14(23):10375-10386. doi: 10.1039/d3fo03847e.

Abstract

Urolithin A (Uro-A), an intestinal microbiota metabolite of ellagitannin, has anti-aging properties. Through the direct intake of ellagitannin (or ellagic acid) and strains capable of producing Uro-A, the transformation of Uro-A in vivo is a potential method to develop anti-aging preparations. Therefore, this study aimed to investigate the dose-response relationship between the colonic infusion of Uro-A and its anti-aging effects. Results indicated that Uro-A exhibited a dose-dependent anti-aging effect in the colon, and the minimum effective dose might be 3.0 mg kg-1 day-1. The main manifestations were that, compared with the model group, 3.0 mg kg-1 day-1 and 15.0 mg kg-1 day-1 of Uro-A can increase forelimb grip strength by 11.87% and 16.72%, respectively, and increase the discrimination index by 92.14% and 238.11%, respectively. Both doses effectively inhibited the D-galactose-induced increase in oxidative stress levels in the body, muscle atrophy, and neuronal apoptosis. Additionally, Uro-A released through the colon could alleviate D-galactose-induced aging in mice by inhibiting NF-κB and mTOR targets, providing significant protection for motor and cognitive functions. These findings provide a theoretical basis for future application and development of ellagitannin (or ellagic acid) in combination with strains capable of producing Uro-A.

MeSH terms

  • Aging
  • Animals
  • Coumarins / metabolism
  • Coumarins / pharmacology
  • Ellagic Acid / metabolism
  • Ellagic Acid / pharmacology
  • Galactose
  • Hydrolyzable Tannins* / metabolism
  • Hydrolyzable Tannins* / pharmacology
  • Mice
  • NF-kappa B* / genetics
  • TOR Serine-Threonine Kinases / genetics

Substances

  • NF-kappa B
  • 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
  • ellagitannin
  • Hydrolyzable Tannins
  • Galactose
  • Ellagic Acid
  • Coumarins
  • TOR Serine-Threonine Kinases