Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications.
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.
Balasubramanyam
M
M
Division of Cell and Molecular Biology, Madras Diabetes Research Foundation, 4 Conran Smith Road, Gopalapuram, Chennai 600 086, India. drbalu@mdrf.org
Koteswari
A Adaikala
AA
Kumar
R Sampath
RS
Monickaraj
S Finny
SF
Maheswari
J Uma
JU
Mohan
V
V
D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D003474:Curcumin / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017382:Reactive Oxygen Species; D011493:Protein Kinase C; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium