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Tocotrienols Activate Nrf2 Nuclear Translocation and Increase the Antioxidant- Related Hepatoprotective Mechanism in
Ahmed Atia1, Nadia S Alrawaiq1, Azman Abdullah1
1Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.
Background:
The most common preparation of tocotrienols is the Tocotrienol-Rich Fraction (TRF). This study aimed to investigate whether TRF induced liver Nrf2 nuclear translocation and influenced the expression of Nrf2-regulated genes.
Methods:
In the Nrf2 induction study, mice were divided into control, 2000 mg/kg TRF and diethyl maleate treated groups. After acute treatment, mice were sacrificed at specific time points. Liver nuclear extracts were prepared and Nrf2 nuclear translocation was detected through Western blotting. To determine the effect of increasing doses of TRF on the extent of liver nuclear Nrf2 translocation and its implication on the expression levels of several Nrf2-regulated genes, mice were divided into 5 groups (control, 200, 500 and 1000 mg/kg TRF, and butylated hydroxyanisole-treated groups). After 14 days, mice were sacrificed and liver RNA was extracted for qPCR assay.
Results:
2000 mg/kg TRF administration initiated Nrf2 nuclear translocation within 30 min, reached a maximum level of around 1 h and dropped to half-maximal levels by 24 h. Incremental doses of TRF resulted in dose-dependent increases in liver Nrf2 nuclear levels, along with concomitant dosedependent increases in the expressions of Nrf2-regulated genes.
Conclusion:
TRF activated the liver Nrf2 pathway resulting in increased expression of Nrf2-regulated cytoprotective genes.
Insights
Tocotrienol-Rich Fraction (TRF) activates the liver Nrf2 pathway, increasing Nrf2 nuclear translocation and the expression of cytoprotective genes in a dose-dependent manner.
Area of Science:
- Biochemistry
- Molecular Biology
- Nutraceuticals
Background:
- Tocotrienols are commonly prepared as Tocotrienol-Rich Fraction (TRF).
- The Nrf2 pathway is a critical regulator of cellular defense mechanisms.
Purpose of the Study:
- To investigate if TRF induces nuclear translocation of Nrf2 in the liver.
- To determine the effect of TRF on the expression of Nrf2-regulated genes.
Main Methods:
- Mice were treated with varying doses of TRF or control substances.
- Liver nuclear extracts were analyzed for Nrf2 translocation using Western blotting.
- Gene expression levels of Nrf2-regulated targets were quantified via qPCR.
Main Results:
- TRF administration led to rapid and dose-dependent Nrf2 nuclear translocation in mouse liver.
- Increased TRF dosage correlated with elevated expression of Nrf2-regulated genes.
- The effect was observed within hours and sustained over 14 days with incremental doses.
Conclusions:
- TRF effectively activates the liver Nrf2 pathway.
- This activation results in the upregulation of Nrf2-regulated cytoprotective genes.
- TRF demonstrates potential as an agent for enhancing cellular protection through the Nrf2 pathway.
