Multiple biological defects caused by calycosin-7-O-β-d-glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

J Appl Toxicol. 2018 Jun;38(6):801-809. doi: 10.1002/jat.3588. Epub 2018 Jan 19.

Abstract

Calycosin-7-O-β-d-glucoside (CG) is an important active isoflavone compound in Radix Astragali that has many bioactivities. However, the toxicological effects and related toxicological mechanism of CG have been rarely documented. The purpose of the present study was to evaluate the toxicity effects of CG on the model organism Caenorhabditis elegans. Some characteristics of the nematode, including lifespan, movement behavior and reproductive capacity, were used to detect the toxic effects of CG on C. elegans. The results showed that CG could shorten the lifespan of C. elegans by up to 25.3% and severely damage the movement of N2 larvae compared with the control group. Moreover, CG could prolong the generation times and reduce the brood sizes. Furthermore, CG promoted the formation of reactive oxygen species (ROS), which caused oxidative stress, increased the mRNA expression of sod-1, sod-2, sod-3, sod-5, ctl-1, ctl-2 and ctl-3, and induced the antioxidant enzymes activities of superoxide dismutase and catalase to scavenge free radicals. However, antioxidant treatment experiments showed that Trolox could reduce the level of ROS caused by CG to the normal state of the control. These results suggested that the generation and elimination of ROS could not restore normal homeostasis in C. elegans treated by CG. These findings indicated that the activation of oxidative damage is one of the most important toxic mechanisms of CG in C. elegans.

Keywords: Caenorhabditis elegans; calycosin-7-O-β-D-glucoside; catalase; oxidative damage; superoxide dismutase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Gene Expression Regulation, Enzymologic
  • Glucosides / toxicity*
  • Isoflavones / toxicity*
  • Longevity / drug effects
  • Movement / drug effects
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism*
  • Reproduction / drug effects
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Time Factors

Substances

  • Caenorhabditis elegans Proteins
  • Glucosides
  • Isoflavones
  • Reactive Oxygen Species
  • calycosin-7-O-beta-D-glucoside
  • Catalase
  • Superoxide Dismutase