Curcumin as “Curecumin”: From kitchen to clinic

Goel, Ajay; Kunnumakkara, Ajaikumar B.; Aggarwal, Bharat B.

doi:10.1016/j.bcp.2007.08.016

Cited by 1,849 publications

(1,325 citation statements)

References 178 publications

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“…Supplementation with Vitamin A and retinoids down-regulated inflammation in EAE and suppressed serum cytokines, such as TNF-a and IL-1, but enhanced IL-10 [42]. Curcumin, a naturally occurring yellow pigment commonly used as a coloring and flavoring spice in food products has been shown to modulate the growth and cellular responses of various immune cells including cytokine production [25,30]. Curcumin also inhibits NF-kB activation in various cells [29].…”

Section: Discussionmentioning

confidence: 99%

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Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine‐protective regulatory T cells

Cong¹,

Wang²,

Konrad³

et al. 2009

Eur J Immunol

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The gut is home to a large number of Treg, with both CD4 1 CD25 1 Treg and bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina propria. It has been shown recently that intestinal mucosal DC are able to induce Foxp3 1 Treg through production of TGF-b plus retinoic acid (RA). However, the factors instructing DC toward this mucosal phenotype are currently unknown. Curcumin has been shown to possess a number of biologic activities including the inhibition of NF-jB signaling. We asked whether curcumin could modulate DC to be tolerogenic whose function could mimic mucosal DC. We report here that curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin-treated DC induced differentiation of naïve CD4 1 T cells into Treg resembling Treg in the intestine, including both CD4 1 CD25 1 Foxp3 1 Treg and IL-10-producing Tr1 cells. Such Treg induction required IL-10, TGF-b and retinoic acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF-b production were involved in the function of such induced Treg. More importantly, these Treg inhibited antigen-specific T-cell activation in vitro and inhibited colitis due to antigen-specific pathogenic T cells in vivo.

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Section: Discussionmentioning

confidence: 99%

“…Curcumin (diferuloylmethane), the major constituent of turmeric powder extracted from the rhizomes of Curcuma longa L., has a long history of medical use in India and Southeast Asia [25]. Curcumin has been shown to exhibit anti-inflammatory, anti-mutagenic, and anti-carcinogenic activity [26].…”

Section: Introductionmentioning

confidence: 99%

Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine‐protective regulatory T cells

Cong¹,

Wang²,

Konrad³

et al. 2009

Eur J Immunol

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“…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][2][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.…”

Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

233

206

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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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“…Curcumin is the active ingredient of turmeric, which is obtained from the roots and rhizomes of the plant Curcuma longa L. Turmeric has been used as a food flavoring and dye and, for many centuries, in traditional Indian, Nepali, and Chinese medicine, for instance, to treat abdominal pain, sprains, fever, and swellings (Eigner and Scholz, 1999;Goel et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Multiple clinical trials are assessing the clinical uses of curcumin and its derivatives (Goel et al, 2008;Gupta et al, 2013a,b).…”

Section: Introductionmentioning

confidence: 99%

Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione

et al. 2014

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We have previously reported that curcumin analogs with a C 7 linker bearing a C 4 -C 5 olefinic linker with a single keto group at C3 (enone linker) display midnanomolar activity against the bloodstream form of Trypanosoma brucei. However, no clear indication of their mechanism of action or superior antiparasitic activity relative to analogs with the original di-ketone curcumin linker was apparent. To further investigate their utility as antiparasitic agents, we compare the cellular effects of curcumin and the enone linker lead compound 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (AS-HK014) here. An AS-HK014-resitant line, trypanosomes adapted to AS-HK014 (TA014), was developed by in vitro exposure to the drug. Metabolomic analysis revealed that exposure to AS-HK014, but not curcumin, rapidly depleted glutathione and trypanothione in the wild-type line, although almost all other metabolites were unchanged relative to control. In TA014 cells, thiol levels were similar to untreated wild-type cells and not significantly depleted by AS-HK014. Adducts of AS-HK014 with both glutathione and trypanothione were identified in AS-HK014-exposed wild-type cells and reproduced by chemical reaction. However, adduct accumulation in sensitive cells was much lower than in resistant cells. TA014 cells did not exhibit any changes in sequence or protein levels of glutathione synthetase and g-glutamylcysteine synthetase relative to wild-type cells. We conclude that monoenone curcuminoids have a different mode of action than curcumin, rapidly and specifically depleting thiol levels in trypanosomes by forming an adduct. This adduct may ultimately be responsible for the highly potent trypanocidal and antiparasitic activity of the monoenone curcuminoids.

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Curcumin as “Curecumin”: From kitchen to clinic

Cited by 1,849 publications

References 178 publications

Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine‐protective regulatory T cells

Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine‐protective regulatory T cells

The dark side of curcumin

Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione

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