BioaVailability of Curcumin: Problems and Promises
to lower the IC50 values significantly.77 Further, the curcumin copper complex was equally effective as curcumin against cadmium induced oxidative damage in mice.78 Theoretical calculation of ionization energies of curcumin and curcumin copper complexes have shown that these possess higher reactive oxygen species scavenging ability than does cur- cumin.72 Similarly, it was demonstrated that curcumin- manganese complex exhibited a more potent neuroprotective activity than curcumin both in Vitro and in ViVo suggesting that this complex may be useful as a neuroprotective agent in the treatment of acute brain pathologies associated with NO-induced neurotoxicity and oxidative stress-induced neu- ronal damage such as epilepsy, stroke, and traumatic brain
A vanadyl curcumin complex (VO(cur)2) was
reported to show a 2-fold increase in antirheumatic activity and a 4-fold increase in inhibiting smooth muscle cell proliferation as compared to free curcumin in Vitro. Further, this complex was more effective as an anticancer agent, compared to uncomplexed curcumin.82 Both in Vitro and in ViVo evaluations of a series of indium and gallium complexes of curcumin derivatives and curcumin have shown that the structural modification and/or complex formation of cur- cumin with metal ions may yield gallium and indium curcuminoids with potential therapeutic applications.83 Al- though many curcumin analogues are found to show improved biological activity over curcumin, specific evalu- ations of structural analogues and/or derivatives of curcumin to show improved tissue and plasma distribution are lacking. However, the promising biological effects over curcumin showed by structural modifications throws light into the possibility of modulating bioavailability of curcumin and
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much needs to be done to prove that the improved biological activity of structurally modified curcumin is due to its increased bioavailability.
C5. Others. Biocongugates can increase the cellular uptake and hence better bioavailability of curcumin. For example, BCM-95 (also called Biocurcumax) curcuminoids combined with turmeric oil (turmerons) in a specific propor- tion enhanced the bioavailability (Figure 2c) and showed better absorption into blood and had longer retention time compared to curcumin. This product showed 700% more activity and 7–8 times more bioavailability over curcumin as confirmed by human clinical trials (unpublished data). Currently a multicenter, phase II, randomized, double- blinded, placebo controlled clinical study is ongoing to assess the efficacy and safety of BCM-95 in oral premalignant lesions/cervical cancer (www.bcm95.com). In another study, curcumin bioconjugates containing glycine, alanine, and/or piperic acid were found to show improved antimicrobial properties over curcumin, suggesting increased cellular uptake or reduced metabolism of these bioconjugates result- ing in increased concentration inside the infected cells.84
Curcumin derived from the common food spice turmeric has been used for centuries as a remedy for many ailments. Extensive scientific research over the past decade has shown the ability of this compound to modulate multiple cellular targets and hence possesses preventive and therapeutic value against a wide variety of diseases. Curcumin has a diverse range of molecular targets like transcription factors, growth factors and their receptors, cytokines, enzymes, and genes regulating cell proliferation and apoptosis. One of recent reviews from our group extensively describes the molecular targets of curcumin.85 Despite its demonstrated efficacy and safety, limited curcumin bioavailability continues to be highlighted as a major concern. As detailed in this review, lower serum and tissue levels of curcumin irrespective of the route of administration, rapid metabolism and elimination are major factors curtailing curcumin bioavailability. Modu-
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