Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications

Abstract

There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

A comparative study on the antioxidant and immunomodulatory properties of curcumin conjugated gold nanospheres and free curcumin

“…The ameliorated process of such antioxidant and free radical scavenging properties of cAuNps over free curcumin can be due to their interaction patterns of phenolic-OH and by abstraction of H atom from C12 methylene group of curcumin (Balasubramanyam et al, 2003;Hatcher et al, 2008). The main reason for this phenomenon might be attributed because of the increasing the availability of curcumin conjugated with the metal Au, by which more H atoms are made available to cells.…”

Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction

“…Curcumin is a known antioxidant (44,45) and is known to inhibit Cox-2 activity (46). On the basis of this prior information, our results provide a model for the curcumin action, portraying that the known Cox-2 inhibitory properties of curcumin blunts the PGE 2 production by tumor cells, which eventually prevents the tumor-induced down-regulation of T cell ␥c expression, Jak-3/Stat-5 hypo-phosphorylation, and subsequent death of T cells, although involvement of NFB cannot be ruled out completely as it is known to control nearly 150 genes that include cytokine genes (47) and can be inhibited by PGE 2 (31).…”

Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

“…Curcumin, isolated from turmeric (Curcuma longa L.), contains curcumin as a major component but also contains demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), respectively (4). Extensive research during the last half century has revealed several important functions of curcumin such as antioxidant, anti-inflammatory and anticancer properties (5)(6)(7). Recently, more and more studies have demonstrated the stronger activity of DMC when compared with curcumin in many aspects (8)(9)(10).…”