1. In vivo and in silico studies on the potential role of garden cress oil in attenuating methotrexate-induced inflammation and apoptosis in liver.
- Author
-
Mabrouk DM, El-Akad RH, Afifi AH, Sharaf HA, El-Sharkawy SL, and El Makawy AI
- Subjects
- Animals, Rats, Male, Plant Oils pharmacology, Plant Oils chemistry, Inflammation drug therapy, Inflammation metabolism, Inflammation chemically induced, Tumor Necrosis Factor-alpha metabolism, Gas Chromatography-Mass Spectrometry, Caspase 3 metabolism, Rats, Wistar, Computer Simulation, Methotrexate, Apoptosis drug effects, Molecular Docking Simulation, Liver drug effects, Liver metabolism, Liver pathology, Chemical and Drug Induced Liver Injury drug therapy, Chemical and Drug Induced Liver Injury metabolism, Chemical and Drug Induced Liver Injury pathology, Chemical and Drug Induced Liver Injury prevention & control
- Abstract
Methotrexate (MTX) has been used in high doses for cancer therapy and low doses for autoimmune diseases. It is proven that methotrexate-induced hepatotoxicity occurs even at relatively low doses. It is known that garden cress has anti-inflammatory, antioxidant, and hepatoprotective properties. This study investigates the potential alleviating effect of garden cress oil (GCO) against MTX-induced hepatotoxicity in rats. The chemical composition of GCO was assessed using GC/MS analysis. Liver damage was studied using hepatotoxicity biomarkers, molecular, and histological analysis. Also, the effects of GCO on TNF-α and caspase-3 proteins were evaluated through molecular docking studies. The results demonstrated that MTX caused liver damage, as seen by elevated levels of the liver enzymes ALT, AST, and ALP. Likewise, MTX showed clear signs of apoptosis, such as increased mRNA expression levels of BAX, Caspase-3, and P53, and increased liver inflammation indicated by higher levels of TNF-α expression. MTX exhibited significant liver damage, as demonstrated by histological examination. Treatment with GCO effectively alleviated the apoptotic effects of MTX, provided protection against inflammation, and restored histological alterations. GC/MS metabolite profiling of garden cress oil revealed the presence of several phytoconstituents, including tocopherols, erucic acid, sesamolin, linoleic acid, vaccenic acid, oleic acid, stearic acid, and palmitic acid, that showed strong binding affinities toward TNF-α and caspase-3 proteins in molecular docking studies, which could explain the anti-apoptotic and anti-inflammatory potential of GCO., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The animal experiments were approved by the Ethics Committee of the National Research Centre (Approval No. 09410125)., (© 2025. The Author(s).)
- Published
- 2025
- Full Text
- View/download PDF