Ratio of cellular GSH/GSSG indicating intracellular redox status
plays an important role in redox-dependent signaling pathway.
Compared β-thalassemia/Hb E patients with normal subjects [25],
the ratios of GSH/GSSG were markedly decreased whereas ROS levels
were highly elevated, and it was also found that activities of
glutamate-cysteine ligase, the enzyme involved in the rate-limiting
step of glutathione synthesis, increased approximately 2-fold in
patients. Decreased GSH/GSSG ratio results in upregulation of several
enzymes or proteins involved in redox system including SOD, GSH-Px,
glutamate-cysteine ligase, thioredoxin reductase, and metallothionein
[52]. Another mode of action, curcumin is able to raise GSH/GSSG
ratio by increasing cellular GSH content via stimulating Nrf2
expression [53,54] followed by raising Nrf2 nuclear translocation
[55] and finally, increasing the expression of glutamate-cysteine
ligase [56]. The antioxidant activity of curcuminoids resulted in a
significant decrease in the antioxidant enzymes SOD and GSH-Px
(pb0.001) concomitant with an increase in GSH levels in RBC and a
decrease in the percentage of MHb throughout the period of treatment.