A curcumin-diglutaric acid conjugated prodrug with improved water solubility and antinociceptive properties compared to curcumin

Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-kappaB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer's disease.

Curcumin is the active ingredient of turmeric. It is widely used as a kitchen spice and food colorant throughout India, Asia and the Western world. Curcumin is a major constituent of curry powder, to which it imparts its characteristic yellow colour. For over 4000 years, curcumin has been used in traditional Asian and African medicine to treat a wide variety of ailments. There is a strong current public interest in naturally occurring plant-based remedies and dietary factors related to health and disease. Curcumin is non-toxic to human subjects at high doses. It is a complex molecule with multiple biological targets and different cellular effects. Recently, its molecular mechanisms of action have been extensively investigated. It has anti-inflammatory, antioxidant and anti-cancer properties. Under some circumstances its effects can be contradictory, with uncertain implications for human treatment. While more studies are warranted to further understand these contradictions, curcumin holds promise as a disease-modifying and chemopreventive agent. We review the evidence for the therapeutic potential of curcumin from in vitro studies, animal models and human clinical trials.

Commercially available curcumin, a bright orange-yellow color pigment of turmeric, consists of a mixture of three curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. These were isolated by column chromatography and identified by spectroscopic studies. The purity of the curcuminoids was analyzed by an improved HPLC method. HPLC separation was performed on a C(18) column using three solvents, methanol, 2% AcOH, and acetonitrile, with detection at 425 nm. Four different commercially available varieties of turmeric, namely, Salem, Erode, Balasore, and local market samples, were analyzed to detect the percentage of these three curcuminoids. The percentages of curcumin, demethoxycurcumin, and bisdemethoxycurcumin as estimated using their calibration curves were found to be 1.06 +/- 0.061 to 5.65 +/- 0.040, 0.83 +/- 0.047 to 3.36 +/- 0.040, and 0.42 +/- 0.036 to 2.16 +/- 0.06, respectively, in four different samples. The total percentages of curcuminoids are 2.34 +/- 0.171 to 9.18 +/- 0.232%.