Researchers from Gansu University of Chinese Medicine synthesized nitroxide radical–modified rhein derivatives to target the Keap1-Nrf2 antioxidant pathway. Among them, compound 4b displayed potent DPPH and ABTS free radical scavenging, protected L02 hepatocytes under oxidative stress, and extended Caenorhabditis elegans lifespan by over 40%, enhancing stress tolerance and antioxidant enzyme activity.
Key points
- Design and synthesis of rhein nitroxide derivatives via DCC/DMAP coupling at the 3-carboxyl position.
- Compound 4b exhibits IC₅₀ values of 0.51 mM (DPPH) and 0.12 mM (ABTS) and restores 95.4% viability in H₂O₂-challenged L02 hepatocytes.
- In C. elegans, 300 µM 4b increases mean lifespan by 41%, enhances stress resistance, reduces ROS/MDA, and elevates GSH levels.
Why it matters: This derivative offers a novel, targeted Keap1-Nrf2 modulation approach with strong anti-aging potential and improved antioxidant activity.
Q&A
- What is the Keap1-Nrf2 pathway?
- Why use C. elegans to test anti-aging compounds?
- What are DPPH and ABTS assays measuring?
- How does compound 4b compare with parent rhein?