A Realistic View on -The Essential Medicinal Chemistry of Curcumin-
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The review paper entitled “The Essential Medicinal Chemistry of Curcumin”, published in the Journal of Medicinal Chemistry, by Nelson et al.1 is a well-designed paper, presenting a new (and negative) approach to the well-known biologically active compound; curcumin. Although some arguments throughout this paper are completely true, the approach of the authors is unfortunately far from impartial, and many of the conclusions the authors draw from some of their referred papers are especially hard to accept. On page 1621, line 11, the authors mention that the in vivo stability of curcumin is T1/2 < 5 min and F < 1% by referring to the research papers of Wang et al.2 and Yang et al.3 (refs 27 and 28 of the original paper). Interestingly, neither Wang nor Yang et al. directly report these values as the half-life of curcumin, which makes this a very biased supposition of the authors. The paper, published by Wang et al., reports the stability of curcumin in buffer solvents at laboratory conditions and in rat blood circulation. Since it is impossible to directly dissolve curcumin in water, curcumin was dissolved in methanol and then diluted with a buffer, and the amount of curcumin was measured in HPLC at different intervals. It is obvious that curcumin will start precipitating upon dilution with a buffer. Thus, it is doubtful that the sample injected in HPLC or administered to rats includes the supposed amount of curcumin. Yang et al. also do not report the half-life of curcumin below 5 min. This paper reports the elimination period as 28.1 ± 5.6 and 44.5 ± 7.5 min for 500 mg/kg, p.o. and 10 mg/kg, i.v. of curcumin, respectively. It is noteworthy that the half-life results are reported by the studies made in rats, not human studies. A rat weighing 400 g has a total blood volume of approximately 25.6 mL,4 and the human blood volume is approximately 5.5 L. The half-life measurements of the compound during blood circulation were made without considering the insolubility of curcumin in buffer solutions or the stability measurements in rat blood circulation and therefore do not accurately illustrate the fate of curcumin upon circulation within human blood. More interestingly, the authors acknowledge that the half-life of curcumin with pH 7.4 and 37 °C in human blood is 360−480 min in Supplemental Table 2 of ref 1. However, they report its stability as T1/2 < 5 min on page 1621, left column line 11.