Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

Choudhury, Ambar Kumar; Raja, S.; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

doi:10.3390/antiox4040750

Cited by 43 publications

(22 citation statements)

References 38 publications

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“…But the poor oral bioavailability of curcumin contributed by its insolubility, instability, poor absorption, and rapid biotransformation has made it a typical class IV BCS molecule with poor pharmacokinetics [ 14 , 15 ]. A number of enhanced bioavailable formulations of curcumin as demonstrated by the enhanced plasma concentration of curcumin metabolites (glucuronide and sulfate conjugates of curcuminoids and their reduced forms) have been reported and are even available commercially [ 16 – 19 ]. However, recent studies demonstrated poor membrane permeability and lack of anti-inflammatory, antiproliferative, and antioxidant activities of curcumin glucuronides, the major metabolites of curcumin [ 15 , 20 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study

Krishnareddy

Thomas²,

Nair

et al. 2018

BioMed Research International

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Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry No. CTRI/2018/03/012385.

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Section: Introductionmentioning

confidence: 99%

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study

Krishnareddy

Thomas²,

Nair

et al. 2018

BioMed Research International

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“…Curcumin has been used in traditional Chinese medicine for a long time in Taiwan, China and India ( 10 ). The pharmacological effects of curcumin include anti-amyloid ( 11 ), anti-bacterial ( 12 ), anti-depressant ( 13 ), anti-inflammatory ( 14 ), anti-oxidant ( 15 ), anti-diabetes ( 16 ) and anticancer properties ( 17 , 18 ). In addition, curcumin has been found to affect several anticancer signaling pathways such as inhibition of cancer cell proliferation ( 19 , 20 ) and induction of cell cycle arrest ( 21 ), apoptosis ( 22 ) or autophagy ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study

et al. 2017

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Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells. After 24-h treatment with MTH-3, a concentration-dependent decrease in MDA-MB-231 cell viability was observed, and the IC50 value was 5.37±1.22 μM. MTH-3 significantly triggered G2/M phase arrest and apoptosis in MDA-MB-231 cells. Within a 24-h treatment, MTH-3 decreased the CDK1 activity by decreasing CDK1 and cyclin B1 protein levels. MTH-3-induced apoptosis was further confirmed by morphological assessment and Annexin V/PI staining assay. Induction of apoptosis caused by MTH-3 was accompanied by an apparent increase of DR3, DR5 and FADD and, as well as a marked decrease of Bcl-2 and Bcl-xL protein expression. MTH-3 also decreased the protein levels of Ero1, PDI, PERK and calnexin, as well as increased the expression of IRE1α, CHOP and Bip that consequently led to ER stress and MDA-MB-231 cell apoptosis. In addition, MTH-3-treated cells were involved in the autophagic process and cleavage of LC3B was observed. MTH-3 enhanced the protein levels of LC3B, Atg5, Atg7, Atg12, p62 and Beclin-1 in MDA-MB-231 cells. Finally, DNA microarray was carried out to investigate the level changes of gene expression modulated by MTH-3 in MDA-MB-231 cells. Taken together, our results suggest that MTH-3 might be a novel therapeutic agent for the treatment of triple-negative breast cancer in the near future.

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“…The in vitro study revealed that CUR-NP is solubilized in mixed micelles and the high solubilization capacity of CUR-NP leads to higher intestinal absorption of CUR following oral administration. Since CURG is less potent in terms of antioxidant activity and antitumor effects compared to CUR, 8,43 it is desirable to use a NP formulation that not only increases intestinal absorption but also decreases the metabolic degradation and conversion of CUR to other metabolites to further improve the bioavailability of CUR. Overall, additional in vitro and in vivo studies are needed to develop a better understanding of the absorption, metabolism, and overall effects of CUR and CUR-NP in the body.…”

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confidence: 99%

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Harigae¹,

Nakagawa²,

Miyazawa³

et al. 2016

IJN

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Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

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Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

Cited by 43 publications

References 38 publications

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study

Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

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