## 4 Discussion  
Our review identified numerous beneficial effects oftoctrienols on many parameters regarding both the brain and heart. Doctorienols, either used as individual isomers or when combined with othertoctrienols andtocpherol isomers, have various positive impacts as neuroprotective and cardioprotective agents. [PERSON] et al. [18] reported that both \(\alpha\)-tocotrienol and \(\gamma\)-tocopherol were more potent than \(\alpha\)-tocopherol in cerebral protection, as evidenced by significant reductions of infarct volume. Similarly, [PERSON] et al. [19] found a remarkable reduction in infarct volume in the \(\alpha\)-tocotrienol-treated group. The mechanism of neuroprotection might be attributable to the ability oftoctrienols to reverse oxidative stress conditions. Cerebral I/R injury causes the excessive generation of reactive oxygen species (ROS), primarily from the electron transport chain [25]. ROS interacts with various cellular  
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Author** & **IS** & **HR** & **CF** & **AF** & **AOR** & **LVDP** & **LV dp/dt** \\ \hline [PERSON] [15] & \(\downarrow\) & & NS & \(\uparrow\) & & \(\uparrow\) & \(\uparrow\) \\ [PERSON] [14] & \(\downarrow\) & & NS & \(\uparrow\) & & \(\uparrow\) \\ [PERSON] [13] & & NS & NS & \(\uparrow\) & NS & \\ [PERSON] [12] & & & NS & \(\uparrow\) & NS & \\ [PERSON] [16] & & & & & \(\uparrow\) & NS & \\  &  
components, including DNA, proteins, and lipids, as evidenced by the significant increment of oxidative markers of 8-hydroxy-2'-deoxyguanosine (8-OHdG), nitrotyrosine, and 4-hydroxy-2-nonenal (4-HNE), respectively [19; 21]. Membrane disruption following the insult causes the leakage of intracellular components, such as lactate dehydrogenase (LDH) [19; 21]. The endogenous antioxidant system comprises catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S transferase (GST), and superoxide dismutase (SOD), which are distributed unevenly in the different brain regions [26]. SOD plays an essential role in converting superoxide into hydrogen peroxide, while CAT, GPx, and GST act in concert to neutralize hydroperoxides [26]. On the other hand, GR serves as a GSH regenerator, reducing the GSSG by transferring an electron from nicotinamide adenine dinucleotide phosphate (NADPH) to GSSG [26]. Cerebral I/R injury has been shown to affect antioxidant enzymes differently, depending on the region and duration of the insult. For instance, GR activity is reduced during ischemia in the cerebral cortex, cerebellum, and hippocampus but becomes elevated at one hour following reperfusion [26]. In contrast, [PERSON] et al. [27] reported negligible hippocampus changes during ischemia, with a reperfusion period of up to 24 h. The inconsistent results might be attributable to the different durations of ischemia and probably to the different animal models [26; 27]. Moreover, during the first six hours of reperfusion, the levels of GSH significantly decreased, along with a notable increase in GSSG levels. GSSG is a toxic metabolite and can be transported away via the multidrug resistance-associated protein 1 (MRP1) [21]. [PERSON] et al. [21] reported that the I/R injury contributed to the increase in GSSG levels and MRP1 expression. In contrast, MRP1-deficient mice had significantly higher GSSG accumulation and infarct volume than non-deficient mice. \(\alpha\)-tocotrienol upregulates MRP1, attenuating the elevation of the intracellular GSSG level and, thus, reducing the infarct volume [19; 21]. Three included studies utilized a fixed-dose preparation of locotrienols or in combination with locopherol [17; 20; 21]. [PERSON] et al. [20] used a canine model to elucidate the potential mechanism of combined locotrienols in stroke via collateral circulation and reported significant improvements in cytotoxic edema and infarct volume in the first hour following the initiation of reperfusion. Furthermore, the infarct volume remained significantly lower in the combined locotrienols group at 24 h [20].