Ruscogenin Protects Against Deoxynivalenol-Induced Hepatic Injury by Inhibiting Oxidative Stress, Inflammation, and Apoptosis Through the Nrf2 Signaling Pathway: An In vitro Study

Hany Elsawy; Peramaiyan Rajendran; Azza Mahmoud Sedky; Manal Alfwuaires

doi:10.4103/sjmms.sjmms_725_21

Ruscogenin Protects Against Deoxynivalenol-Induced Hepatic Injury by Inhibiting Oxidative Stress, Inflammation, and Apoptosis Through the Nrf2 Signaling Pathway: An In vitro Study

Saudi J Med Med Sci. 2022 Sep-Dec;10(3):207-215. doi: 10.4103/sjmms.sjmms_725_21. Epub 2022 Aug 22.

Authors

Hany Elsawy^{1

2}, Peramaiyan Rajendran³, Azza Mahmoud Sedky^{3

4}, Manal Alfwuaires³

Affiliations

¹ Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
³ Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
⁴ Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt.

Abstract

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.

Keywords: Apoptosis; Nrf2; deoxynivalenol; hepatotoxicity; oxidative stress; ruscogenin.