Unraveling Curcumin Degradation

Gordon, Odaine N.; Luis, Paula B.; Sintim, Herman O.; Schneider, Claus

doi:10.1074/jbc.m114.618785

Cited by 135 publications

(96 citation statements)

References 57 publications

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“…52 For example, a recently identified degradation product of 1 is a spiroepoxide, which is highly sensitive to acids and reacts readily with thiols. 53 This report indirectly emphasizes the relevance of dynamic RC by hypothesizing that the polypharmacology of 1 may in part, or even largely, be due to the sum of its degradation products.…”

Section: Curcumin Is a Pains Imps And Poor Lead Compoundmentioning

confidence: 93%

The Essential Medicinal Chemistry of Curcumin

et al. 2017

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Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

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Section: Curcumin Is a Pains Imps And Poor Lead Compoundmentioning

confidence: 93%

The Essential Medicinal Chemistry of Curcumin

et al. 2017

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“…82 The polyphenolic compound, curcumin is only slightly soluble in an aqueous environment, experiences degradation at alkaline pH, rapidly metabolized and conjugated in the liver (curcumin sulfate and curcumin glucuronide), undergoes rapid systemic elimination, is excreted in feces, demonstrates poor tissue absorption, and characterized as a Class II drug 83–85 . In vitro application as a pharmaceutical agent is challenged by curcumin’s degradation and in vivo administration results in decreased efficacy because of metabolic changes.…”

Section: Introductionmentioning

confidence: 99%

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

2015

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More than 230,000 diagnosed cases of invasive breast cancer in women was estimated in 2014 and an expected 40,000 deaths attributed to the aggressive carcinoma. An effective approach to diminish the morbidity and mortality of breast cancer is the development of chemopreventive and chemotherapeutic agents. Nutraceuticals have demonstrated their ability to proficiently halt carcinogenesis. The administration of natural compounds able to effectively serve as chemoprevention and chemotherapeutics without causing harm or adverse effects is imperative. Curcumin derived from the rhizome of Curcuma longa L., is a common spice of India, used for centuries because of its medicinal properties. The main component of curcumin possesses a wide range of biological activities; anti-proliferative, anti-inflammatory, and apoptotic characteristics modulated through the inactivation of pathways such as EGK and Akt/mTOR. In addition, curcumin alters the expression of cytokines, transcription factors, and enzymes involved in cell vitality. The in vivo application of curcumin in breast cancer is hindered by its limited bioavailabiity. The synthesis of curcumin analogues and delivery via nanoparticles has demonstrated enhanced bioavailability of curcumin in the malignancy. This review focuses on recent developments in the use of curcumin, curcumin analogues, and novel delivery systems as a preventive and therapeutic method for breast cancer.

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“…2B). Formation of a spiroepoxide suggested that the reaction proceeded analogous to the oxidative transformation of curcumin (21). When curcumin-glucuronide was transformed using the oxidizing agent potassium ferricyanide (K 3 Fe(CN) 6 ) a similar decrease at 430 nm and increase at ≈260 nm were observed (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The major pathway of non-enzymatic degradation of curcumin at physiological pH is an oxidative transformation leading to dioxygenated bicyclopentadione (BCP) diastereomers (Fig. 1B) (21). Oxidative transformation of curcumin occurs spontaneously as autoxidation and can also be catalyzed by the peroxidase activity of cyclooxygenase-2 (10).…”

Section: Introductionmentioning

confidence: 99%

Oxidative metabolism of curcumin-glucuronide by peroxidases and isolated human leukocytes

Luis

Gordon

Nakashima

et al. 2017

Biochemical Pharmacology

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Conjugation with glucuronic acid is a prevalent metabolic pathway of orally administrated curcumin, the bioactive diphenol of the spice turmeric. The major in vitro degradation reaction of curcumin is autoxidative transformation resulting in oxygenation and cyclization of the heptadienedione chain to form cyclopentadione derivatives. Here we show that curcumin-glucuronide is much more stable than curcumin, degrading about two orders of magnitude slower. Horseradish peroxidase-catalyzed oxidation of curcumin-glucuronide occurred at about 80% of the rate with curcumin, achieving efficient transformation. Using LC-MS and NMR analyses the major products of oxidative transformation were identified as glucuronidated bicyclopentadione diastereomers. Cleavage into vanillin-glucuronide accounted for about 10% of the products. Myeloperoxidase and lactoperoxidase oxidized curcumin-glucuronide whereas tyrosinase and xanthine oxidase were not active. Phorbol ester-activated primary human leukocytes showed increased oxidative transformation of curcumin-glucuronide which was inhibited by the peroxidase inhibitor sodium azide. These studies provide evidence that the glucuronide of curcumin is not an inert product and may undergo further enzymatic and non-enzymatic metabolism. Oxidative transformation by leukocyte myeloperoxidase may represent a novel metabolic pathway of curcumin and its glucuronide conjugate.

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Unraveling Curcumin Degradation

Cited by 135 publications

References 57 publications

The Essential Medicinal Chemistry of Curcumin

The Essential Medicinal Chemistry of Curcumin

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

Oxidative metabolism of curcumin-glucuronide by peroxidases and isolated human leukocytes

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