Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Sandur, Santosh K.; Ichikawa, Haruyo; Pandey, Manoj K.; Kunnumakkara, Ajaikumar B.; Sung, Bokyung; Sethi, Gautam; Aggarwal, Bharat B.

doi:10.1016/j.freeradbiomed.2007.05.009

Cited by 272 publications

(189 citation statements)

References 63 publications

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“…40,[44][45][46][47][48] Experimental studies have demonstrated that, although low concentrations of curcumin induce antioxidant effects, higher concentrations of this compound increase the cellular levels of ROS. 4,9,23,28,[49][50][51][52][53] The presence of 2 a,b-unsaturated ketones in the chemical structure of curcumin may also mediate some of its negative properties. These chemical groups are known to react covalently with exposed thiol groups of cysteine residues of proteins through a reaction termed Michael addition.…”

Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

297

210

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Dear Editor,Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa. The powdered rhizome of this plant, called turmeric, is a common ingredient in curry powders and has a long history of use in traditional Asian medicine for a wide variety of disorders. In the last decade a large number of reports have been published on the beneficial effects of curcumin, and it has repeatedly been claimed that this natural product is efficient and safe for the prevention and treatment of several diseases including cancer. 1-3 It is not surprising, therefore, that curcumin is currently sold as a dietary supplement and that numerous clinical trials are ongoing or recruiting participants to evaluate curcumin activity. But there is accumulating evidence that curcumin may not be so effective and safe. Because such evidence is not generally acknowledged, the purpose of this letter is to briefly review the negative properties of curcumin so that they can be balanced against its beneficial effects.Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies in which curcumin was tested at concentrations in the micromolar range. Several reports have demonstrated, however, that the plasma concentrations of curcumin in people taking relatively high oral doses of this compound are very low, typically in the nanomolar range (reviewed in Ref. 4). For instance, a recent study examined the pharmacokinetics of a curcumin preparation in 12 healthy human volunteers 0.25-72 hr after an oral dose of 10 or 12 g. Using a high-performance liquid chromatography assay with a limit of detection of 50 ng mL À1 , only 1 subject had detectable free curcumin at any of the time points assayed. 5 The fact that curcumin also undergoes extensive metabolism in intestine and liver 6,7 means that high concentrations of curcumin cannot be achieved and maintained in plasma and tissues after oral ingestion. This is a major obstacle for the clinical development of this agent and suggests that the therapeutic potential of oral curcumin is limited. The low clinical efficiency of curcumin in the treatment of several chronic diseases such as Alzheimer's disease and cardiovascular diseases has been discussed recently. 8 As far as cancer is concerned, in vitro studies have demonstrated that cancer cells do not die unless they are exposed to curcumin concentrations of 5-50 lM for several hours. 4,9,10 Because of its poor bioavailability, these concentrations are not achieved outside the gastrointestinal tract when curcumin is taken orally. Because of its extensive metabolism in intestine and liver, these concentrations cannot be maintained for several hours in the gastrointestinal tract. This suggests that the chemotherapeutic potential of oral curcumin is limited even for the treatment of cancers of the gastrointestinal tract. Accordingly, when 15 patients with advanced colorectal cancer were treated with curcumin at daily doses of 3.6 g for up to 4 months, no partial responses to treatment or decreases in tu...

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Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

297

210

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“…For several decades curcumin has been widely used as a food coloring ingredient for its yellowish color. In the last 10 years, several in vitro and in vivo studies have reported that curcumin possesses significant pharmacological actions, such as anti-tumor effects, anti-inflammatory effects and induction of apoptosis of cancer cells (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Effect of curcumin on the proliferation and apoptosis of hepatic stellate cells

Shu

et al. 2009

Braz J Med Biol Res

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“…The study further concludes that relaxation of porcine arterial rings by curcumin is mediated through NO, cGMP and β-adrenoreceptors (Xu et al, 2007). Curcumin has been shown to affect number of molecular targets including transcription factor p53 and cyclin-dependent kinase inhibitor (CDKI) p21 via its role as a pro-and antioxidant (Sandur et al, 2007). Our studies indicate that combination of curcumin + NOC-18 increased the accumulation of transcription factor p53 with concomitant increase in the protein levels of CDKI p21 and cardiac specific protein MLC2 and troponin I compared to either of the two agents alone.…”

Section: Tablementioning

confidence: 75%

Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway

et al. 2012

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Curcumin, an active ingredient of dietary spice used in curry, has been shown to exhibit anti-oxidant, anti-inflammatory and anti-proliferative properties. Using EB directed differentiation protocol of H-9 human embryonic stem (ES) cells; we evaluated the effect of curcumin (0-20 μmol/L) in enhancing such differentiation. Our results using real time PCR, western blotting and immunostaining demonstrated that curcumin significantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5, cardiac troponin I, myosin heavy chain, and endothelial nitric oxide synthase during ES cell differentiation. Furthermore, an NO donor enhanced the curcumin-mediated induction of NKx2.5 and other cardiac specific proteins. Incubation of cells with curcumin led to a dose dependent increase in intracellular nitrite to the same extent as giving an authentic NO donor. Functional assay for second messenger(s) cyclic AMP (cAMP) and cyclic GMP (cGMP) revealed that continuous presence of curcumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP. Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleotide-degrading enzyme (phosphodiesterase) by curcumin. These studies demonstrate that polyphenol curcumin may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling.

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Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane)

Cited by 272 publications

References 63 publications

The dark side of curcumin

The dark side of curcumin

Effect of curcumin on the proliferation and apoptosis of hepatic stellate cells

Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway

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