Ruscogenin protects against deoxynivalenol-Induced hepatic injury by inhibiting oxidative stress, inflammation, and apoptosis through the Nrf2 signaling pathway: An In vitro study
Hany Elsawy1, Peramaiyan Rajendran2, Azza Mahmoud Sedky3, Manal Alfwuaires2
1 Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
2 Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia
3 Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt
Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982
Source of Support: None, Conflict of Interest: None
Background: Deoxynivalenol (DON) is a trichothecene mycotoxin with demonstrated cytotoxicity in several cell lines and animals, primarily owing to inflammation and reactive oxygen species accumulation. Ruscogenin (RGN), a steroidal sapogenin of Radix Ophiopogon japonicus, has significant anti-thrombotic/anti-inflammatory effects.
Objective: The aim of this study was to assess the protective role of RGN against DON-induced oxidative stress, which occurs through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and is regulated by phosphoinositide 3-kinases/protein kinase B (PI3K/AKT).
Methods: The effects were examined using the HepG2 cell line. RGN and DON were suspended in serum-free medium. Cells were seeded onto plates, and then RGN, DON, or both were added over 24 h in triplicates for each group.
Results: RGN conferred protection against DON-exhibited cytotoxicity against HepG2 cells. RGN pretreatment downregulated the expression of DON-induced TNF-α and COX-2 and the formation of reactive oxygen species in a dose-dependent manner. RGN upregulated the expression of Nrf2 and its antioxidant proteins as well as mRNA levels of HO-1/NQO-1/HO-1/Nrf2. Similarly, treatment with DON + RGN resulted in upregulation of the pI3K/pAKT signaling pathway in a dose-dependent manner. Finally, RGN was also found to inhibit the DON-induced apoptosis by upregulating the levels of cleaved proteins and downregulating the expression of Bcl2.
Conclusion: The study demonstrates that RGN suppresses hepatic cell injury induced by oxidative stress through Nrf2 via activation of the pI3K/AKT signaling pathway.