Degradation of Curcumin: From Mechanism to Biological Implications

Schneider, Claus; Gordon, Odaine N.; Edwards, R. A.; Luis, Paula B.

doi:10.1021/acs.jafc.5b00244

Cited by 344 publications

(288 citation statements)

References 61 publications

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“…However, this compound is highly unstable and its bioavailability is very low. It is supposed that, like the degradation products of delphinidin, those of curcumin are also active (45). Experiments need to be performed to better understand the metabolism and degradation pathways of these polyphenols and determine their modes of action.…”

Section: Discussionmentioning

confidence: 99%

Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action

Calland

Sahuc

Belouzard

et al. 2015

J Virol

125

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Despite the validation of direct-acting antivirals for hepatitis C treatment, the discovery of new compounds with different modes of action may still be of importance for the treatment of special patient populations. We recently identified a natural molecule, epigallocatechin-3-gallate (EGCG), as an inhibitor of hepatitis C virus (HCV) targeting the viral particle. The aim of this work was to discover new natural compounds with higher anti-HCV activity than that of EGCG and determine their mode of action. Eight natural molecules with structure similarity to EGCG were selected. HCV JFH1 in cell culture and HCV pseudoparticle systems were used to determine the antiviral activity and mechanism of action of the compounds. We identified delphinidin, a polyphenol belonging to the anthocyanidin family, as a new inhibitor of HCV entry. Delphinidin inhibits HCV entry in a pangenotypic manner by acting directly on the viral particle and impairing its attachment to the cell surface. Importantly, it is also active against HCV in primary human hepatocytes, with no apparent cytotoxicity and in combination with interferon and boceprevir in cell culture. Different approaches showed that neither aggregation nor destruction of the particle occurred. Cryo-transmission electron microscopy observations of HCV pseudoparticles treated with delphinidin or EGCG showed a bulge on particles that was not observed under control conditions. In conclusion, EGCG and delphinidin inhibit HCV entry by a new mechanism, i.e., alteration of the viral particle structure that impairs its attachment to the cell surface. IMPORTANCEIn this article, we identify a new inhibitor of hepatitis C virus (HCV) infection, delphinidin, that prevents HCV entry. This natural compound, a plant pigment responsible for the blue-purple color of flowers and berries, belongs to the flavonoid family, like the catechin EGCG, the major component present in green tea extract, which is also an inhibitor of HCV entry. We studied the mode of action of these two compounds against HCV and demonstrated that they both act directly on the virus, inducing a bulging of the viral envelope. This deformation might be responsible for the observed inhibition of virus attachment to the cell surface. The discovery of such HCV inhibitors with an unusual mode of action is important to better characterize the mechanism of HCV entry into hepatocytes and to help develop a new class of HCV entry inhibitors. H epatitis C is a major health problem, with as many as 130 million people chronically infected worldwide (1). It is caused by hepatitis C virus (HCV), which has a high propensity to establish a persistent infection. Chronic hepatitis C can lead to the development of cirrhosis and hepatocellular carcinoma. Recent improvements in the standard of care, with direct-acting antivirals (DAAs) that inhibit HCV NS3/4A protease, NS5B polymerase, or NS5A, and now without interferon (IFN), which causes severe adverse effects, have raised the hope that HCV infection can be managed efficiently in cou...

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Section: Discussionmentioning

confidence: 99%

Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action

Calland

Sahuc

Belouzard

et al. 2015

J Virol

125

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“…Curcumin is known to degrade spontaneously by autoxidation in culture medium. 40 Although the 24 hours of incubation was performed in the dark, the degradation of curcumin is still expected. 41 This makes it difficult to calculate the percentage of curcumin released from the fibers based on the concentrations calculated.…”

Section: Thermal Propertiesmentioning

confidence: 99%

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

Mouthuy¹,

Škoc²,

Gašparović³

et al. 2017

IJN

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Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO) filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio). The results from the present study showed that, at low doses (≤0.1%), the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs) compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%). Highly dosed filaments induce either the inhibition of proliferation (with 1%) or cell apoptosis (with 10%) as a result of the concentrations of curcumin found in the medium (9 and 32 μM, respectively), which are near or above the known toxicity threshold of curcumin (~10 μM). Moreover, filaments with 10% curcumin increase the catalase activity and glutathione content in NHDFs, indicating an increased production of reactive oxygen species resulting from the large concentration of curcumin. Overall, this study suggested that PDO electrospun filaments loaded with low amounts of curcumin are more promising compared with higher concentrations for stimulating tissue repair. This study also highlighted the need to explore lower concentrations when using polymers as PDO, such as those with polycaprolactone and other degradable polyesters.

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“…It has been reported that curcumin solubility in aqueous buffer (pH= 5.0) was only 11 ng/mL (7). Curcumin in the form of commercially available curcuminoid mixture is presently under investigation in more than 100 clinical trials (8). Capsules containing curcumin as powder were administered to healthy volunteers (9) as well as to cancer patients (10) in a high dose of 4-12 g/day.…”

Section: Introductionmentioning

confidence: 99%

“…The chemical instability of curcumin under alkaline pH is well documented. Schneider et al published a number of interesting papers in which the degradation of curcumin in aqueous buffer was studied (8). They also studied the degradation mechanism and identified the formed products.…”

Section: Introductionmentioning

confidence: 99%

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Naksuriya

Steenbergen

Toraño

et al. 2016

AAPS J

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Abstract. Curcumin, a phenolic compound, possesses many pharmacological activities and is under clinical evaluation to treat different diseases. However, conflicting data about its stability have been reported. In this study, the kinetic degradation of curcumin from a natural curcuminoid mixture under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. Moreover, the degradation of pure curcumin at some selected conditions was also determined. To fully solubilize curcumin and to prevent precipitation of curcumin that occurs when low concentrations of co-solvent are present, a 50:50 (v/v) aqueous buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that degradation of curcumin both as pure compound and present in the curcuminoid mixture followed first order kinetic reaction. It was further shown that an increasing pH, temperature, and dielectric constant of the medium resulted in an increase in the degradation rate. Curcumin showed rapid degradation due to autoxidation in aqueous buffer pH=8.0 with a rate constant of 280×10 -3 h -1, corresponding with a half-life (t 1/2 ) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product. Importantly, curcumin loaded as curcuminoid mixture in ω-methoxy poly (ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (mPEG-HPMA-Bz) polymeric micelles and in Triton X-100 micelles was about 300-500 times more stable than in aqueous buffer. Therefore, loading of curcumin into polymeric micelles is a promising approach to stabilize this compound and develop formulations suitable for further pharmaceutical and clinical studies.

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Degradation of Curcumin: From Mechanism to Biological Implications

Cited by 344 publications

References 61 publications

Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action

Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

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