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

Overview

Journal Saudi J Med Med Sci

Specialty General Medicine

Date 2022 Oct 17

PMID 36247053

Authors

Hany Elsawy

Peramaiyan Rajendran

Azza Mahmoud Sedky

Manal Alfwuaires

Affiliations

Soon will be listed here.

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 , 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.

Citing Articles

Ruscogenin Attenuates Ulcerative Colitis in Mice by Inhibiting Caspase-1-Dependent Pyroptosis via the TLR4/NF-κB Signaling Pathway.

Li J, Wu H, Zhou J, Jiang R, Zhuo Z, Yang Q Biomedicines. 2024; 12(5).

PMID: 38790951 PMC: 11117655. DOI: 10.3390/biomedicines12050989.

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