Investigating The Effects of Triptolide on SKN-1/Nrf2 Pathway in Caenorhabditis elegans
Manashri Tendulkar
Co-Presenters: Individual Presentation
College: The Dorothy and George Hennings College of Science, Mathematics and Technology
Major: Biotechnology (M.S.)
Faculty Research Mentor: Renalison Farias Pereira
Abstract:
Triptolide, a bioactive diterpenoid derived from medicinal plant, has demonstrated potent anti-inflammatory and anticancer properties. However, its high toxicity, frequently linked to oxidative stress, presents significant challenges to its therapeutic use. The Nrf2 pathway, a key regulator of cellular antioxidant defenses, has been implicated in the effects of triptolide. The evidence of triptolide's effects on the Nrf2 pathway is mixed. Some studies suggest it inhibits Nrf2, leading to increased oxidative stress and toxicity, while others indicate it activates Nrf2, enhancing antioxidant defenses in specific disease models. This context-dependent mechanism needs further investigation.Caenorhabditis elegans serves as an effective model for studying oxidative stress responses. Its SKN-1 transcription factor acts as the homolog of Nrf2, enabling a detailed investigation of triptolide’s effects on detoxification and survival pathways. This study aims to determine whether triptolide induces or inhibits the activation of SKN-1 by examining its nuclear localization in response to treatment. Paraquat, a toxic herbicide that generates reactive oxygen species, is used in C. elegans to study oxidative stress-induced cellular damage and death.This study explored the effects of triptolide and paraquat on C. elegans survival and morphology. Paraquat at 5 mM increased mortality by day 3, especially in the co-exposure with the triptolide group, indicating that triptolide worsens its toxicity through enhanced oxidative stress. Triptolide has been shown to reduce survival rates in a dose-dependent manner, with significantly fewer survivors compared to the control group. It also reduces the size of the worms, indicating that triptolide enhances oxidative stress. To further explore these effects, we will use transgenic C. elegans to visualize SKN-1::GFP nuclear localization after exposure to different triptolide concentrations and SKN-1 knockout mutants to confirm the involved pathways.