Jiménez-Flores, L.M.; López-Briones, S.; Macías-Cervantes, M.H.; Ramírez-Emiliano, J.; Pérez-Vázquez, V. A PPARγ, NF-κB and AMPK-Dependent Mechanism May Be Involved in the Beneficial Effects of Curcumin in the Diabetic db/db Mice Liver. Molecules 2014, 19, 8289-8302.
Abstract
Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.
Conclusions
Curcumin regulates the expression of AMPK, PPARγ, and NF-κB, but not of SIRT1 and PGC-1α in the liver of db/db mice; however, these proteins could be activated as discussed prior in the results and discussion section. The study of molecules involved in the disturbance of metabolic pathways may be employed in order to direct appropriate therapeutic strategies for T2DM complications. This study provides a basis to elucidate a possible molecular mechanism of action of curcumin in the liver. The therapeutic potential of curcumin is constrained by limited bioavailability; this could be a relative disadvantage in regards to beneficial curcumin effects. At the age of 15 weeks, the curcumin intervention on db/db mice could be too late to allow a major reversal of complications or improvement from the disease. Further studies are needed to define the ideal timing and procedure to use curcumin in T2DM.
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