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.

OBJECTIVE: This review is aimed to discuss the literature reporting the effects of tocotrienols on osteoclasts, the cells specialized for resorbing bone.

RESULTS: Out of the total 22 studies from the literature search, only 11 of them were identified as relevant, which comprised of eight animal studies, two in vitro studies and only one combination of both. The in vivo studies indicated that tocotrienols improve the bone health and reduce bone loss via inhibition of osteoclast formation and resorption activity, which could be through regulation of RANKL and OPG expression as seen from their levels in the sera. This is well supported by data from the in vitro studies demonstrating the suppression of osteoclast formation and resorption activity following treatment with tocotrienol isomers.