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Regulatory Effects of Curcumin

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (20 January 2024) | Viewed by 19145

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Dr. Jean-Marc Zingg

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Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
Interests: vitamin E; curcumin; signal transduction; gene expression; senescence
Special Issues, Collections and Topics in MDPI journals

Dr. Kiyotaka Nakagawa

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Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8577, Japan
Interests: food function; antioxidant; curcumin; lipid oxidation; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Dr. Taiki Miyazawa

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New Industry Creation Hatchery Center (NICHe), Tohoku University, Sendai 980-8579, Japan
Interests: curcumin; nanoparticles; redox regulation; surfactant; soft matter
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Curcumin, the main bioactive polyphenol present in the turmeric plant Curcuma longa, has beneficial effects for the treatment and prevention of several diseases. Whereas at high experimental concentrations, curcumin may act as antioxidant and affect multiple targets, recent research has revealed regulatory effects even at levels that can be reached by dietary supplementation, and the molecular mechanisms of action are beginning to be resolved. These studies indicate that curcumin and its metabolites may modulate several signal transduction and gene expression pathways by interacting with and affecting the activity of specific enzymes and proteins. Curcumin derivatives, novel pharmacological formulations, nanocarriers, and improved delivery systems have been developed that can enhance the otherwise relatively low bioavailability of curcumin and increase its bioactivity in the human body. During uptake from the diet, curcumin may also modulate the intestinal microbiome, leading to indirect regulatory effects.

In this Special Issue of Antioxidants, the molecular regulatory effects of curcumin are reviewed, and their relevance for the prevention of diseases such as cancer, inflammation, neurodegeneration, cognitive disorders, obesity, atherosclerosis, diabetes, dyslipidemia, and liver diseases such as non-alcoholic steatohepatitis (NASH) is evaluated.

Dr. Jean-Marc Zingg
Dr. Kiyotaka Nakagawa
Dr. Taiki Miyazawa
Guest Editors

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Keywords

curcumin
polyphenol
Curcuma longa
antioxidant
regulatory effects

Published Papers (10 papers)

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Research

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20 pages, 7029 KiB

Open AccessArticle

Protective Effect of Curcumin on D-Galactose-Induced Senescence and Oxidative Stress in LLC-PK1 and HK-2 Cells

by Semiramis Stephania García-Trejo, Tania Gómez-Sierra, Dianelena Eugenio-Pérez, Omar Noel Medina-Campos and José Pedraza-Chaverri

Antioxidants 2024, 13(4), 415; https://doi.org/10.3390/antiox13040415 - 29 Mar 2024

Viewed by 635

Abstract

D-galactose has been widely used as an inducer of cellular senescence and pathophysiological processes related to aging because it induces oxidative stress. On the other hand, the consumption of antioxidants such as curcumin can be an effective strategy to prevent phenotypes related to the enhanced production of reactive oxygen species (ROS), such as aging and senescence. This study aimed to evaluate the potential protective effect of curcumin on senescence and oxidative stress and endoplasmic reticulum stress induced by D-galactose treatment in Lilly Laboratories Culture-Porcine Kidney 1 (LLC-PK1) and human kidney 2 (HK-2) proximal tubule cell lines from pig and human, respectively. For senescence induction, cells were treated with 300 mM D-galactose for 120 h and, to evaluate the protective effect of the antioxidant, cells were treated with 5 µM curcumin for 24 h and subsequently treated with curcumin + D-galactose for 120 h. In LLC-PK1 cells, curcumin treatment decreased by 20% the number of cells positive for senescence-associated (SA)-β-D-galactosidase staining and by 25% the expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and increased by 40% lamin B1 expression. In HK-2 cells, curcumin treatment increased by 60% the expression of proliferating cell nuclear antigen (PCNA, 50% Klotho levels, and 175% catalase activity. In both cell lines, this antioxidant decreased the production of ROS (20% decrease for LLC-PK1 and 10 to 20% for HK-2). These data suggest that curcumin treatment has a moderate protective effect on D-galactose-induced senescence in LLC-PK1 and HK-2 cells. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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27 pages, 5989 KiB

Open AccessArticle

Free Radical Inhibition Using a Water-Soluble Curcumin Complex, NDS27: Mechanism Study Using EPR, Chemiluminescence, and Docking

by Ange Mouithys-Mickalad, Koffi Senam Etsè, Thierry Franck, Justine Ceusters, Ariane Niesten, Hélène Graide, Ginette Deby-Dupont, Charlotte Sandersen and Didier Serteyn

Antioxidants 2024, 13(1), 80; https://doi.org/10.3390/antiox13010080 - 08 Jan 2024

Cited by 1 | Viewed by 1762

Abstract

There is a growing interest in the use of natural compounds to tackle inflammatory diseases and cancers. However, most of them face the bioavailability and solubility challenges to reaching cellular compartments and exert their potential biological effects. Polyphenols belong to that class of molecules, and numerous efforts have been made to improve and overcome these problems. Curcumin is widely studied for its antioxidant and anti-inflammatory properties as well as its use as an anticancer agent. However, its poor solubility and bioavailability are often a source of concern with disappointing or unexpected results in cellular models or in vivo, which limits the clinical use of curcumin as such. Beside nanoparticles and liposomes, cyclodextrins are one of the best candidates to improve the solubility of these molecules. We have used lysine and cyclodextrin to form a water-soluble curcumin complex, named NDS27, in which potential anti-inflammatory effects were demonstrated in cellular and in vivo models. Herein, we investigated for the first time its direct free radicals scavenging activity on DPPH/ABTS assays as well as on hydroxyl, superoxide anion, and peroxyl radical species. The ability of NDS27 to quench singlet oxygen, produced by rose bengal photosensitization, was studied, as was the inhibiting effect on the enzyme-catalyzed oxidation of the co-substrate, luminol analog (L012), using horseradish peroxidase (HRP)/hydrogen peroxide (H₂O₂) system. Finally, docking was performed to study the behavior of NDS27 in the active site of the peroxidase enzyme. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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21 pages, 3155 KiB

Open AccessArticle

The Anti-Oxidant Curcumin Solubilized as Oil-in-Water Nanoemulsions or Chitosan Nanocapsules Effectively Reduces Helicobacter pylori Growth, Bacterial Biofilm Formation, Gastric Cell Adhesion and Internalization

by Antonio Hidalgo, Denisse Bravo, Cristopher Soto, Gabriela Maturana, Jimena Cordero-Machuca, María Carolina Zúñiga-López, Felipe Oyarzun-Ampuero and Andrew F. G. Quest

Antioxidants 2023, 12(10), 1866; https://doi.org/10.3390/antiox12101866 - 16 Oct 2023

Viewed by 1568

Abstract

The bacterium Helicobacter pylori (H. pylori) represents a major risk factor associated with the development of gastric cancer. The anti-oxidant curcumin has been ascribed many benefits to human health, including bactericidal effects. However, these effects are poorly reproducible because the molecule is extremely unstable and water insoluble. Here we solubilized curcumin as either nanoemulsions or chitosan nanocapsules and tested the effects on H. pylori. The nanoemulsions were on average 200 nm in diameter with a PdI ≤ 0.16 and a negative zeta potential (−54 mV), while the nanocapsules were 305 nm in diameter with a PdI ≤ 0.29 and a positive zeta potential (+68 mV). Nanocapsules were safer than nanoemulsions when testing effects on the viability of GES-1 gastric cells. Also, nanocapsules were more efficient than nanoemulsions at inhibiting H. pylori growth (minimal inhibitory concentration: 50 and 75 μM, respectively), whereby chitosan contributed to this activity. Importantly, both formulations effectively diminished H. pylori’s adherence to and internalization by GES-1 cells, as well as biofilm formation. In summary, the demonstrated activity of the curcumin nanoformulations described here against H. pylori posit them as having great potential to treat or complement other therapies currently in use against H. pylori infection. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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21 pages, 5087 KiB

Open AccessArticle

Curcumin Alleviates Singapore Grouper Iridovirus-Induced Intestine Injury in Orange-Spotted Grouper (Epinephelus coioides)

by Yue-Xuan Wang, Sui-Feng Xu, Ye-Wen Wang, Yun-Xiang Jiang, Qi-Wei Qin and Shi-Na Wei

Antioxidants 2023, 12(8), 1584; https://doi.org/10.3390/antiox12081584 - 09 Aug 2023

Viewed by 1650

Abstract

Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper (Epinephelus coioides) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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22 pages, 5216 KiB

Open AccessArticle

Curcumin Administration Improves Force of mdx Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels

by Luisa Gorza, Elena Germinario, Maurizio Vitadello, Irene Guerra, Federica De Majo, Francesca Gasparella, Paolo Caliceti, Libero Vitiello and Daniela Danieli-Betto

Antioxidants 2023, 12(6), 1181; https://doi.org/10.3390/antiox12061181 - 30 May 2023

Cited by 2 | Viewed by 1251

Abstract

The vegetal polyphenol curcumin displays beneficial effects against skeletal muscle derangement induced by oxidative stress, disuse or aging. Since oxidative stress and inflammation are involved in the progression of muscle dystrophy, the effects of curcumin administration were investigated in the diaphragm of mdx mice injected intraperitoneally or subcutaneously with curcumin for 4–12–24 weeks. Curcumin treatment independently of the way and duration of administration (i) ameliorated myofiber maturation index without affecting myofiber necrosis, inflammation and degree of fibrosis; (ii) counteracted the decrease in type 2X and 2B fiber percentage; (iii) increased about 30% both twitch and tetanic tensions of diaphragm strips; (iv) reduced myosin nitrotyrosination and tropomyosin oxidation; (v) acted on two opposite nNOS regulators by decreasing active AMP-Kinase and increasing SERCA1 protein levels, the latter effect being detectable also in myotube cultures from mdx satellite cells. Interestingly, increased contractility, decreased myosin nitrotyrosination and SERCA1 upregulation were also detectable in the mdx diaphragm after a 4-week administration of the NOS inhibitor 7-Nitroindazole, and were not improved further by a combined treatment. In conclusion, curcumin has beneficial effects on the dystrophic muscle, mechanistically acting for the containment of a deregulated nNOS activity. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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14 pages, 3313 KiB

Open AccessArticle

Dietary Curcumin Attenuates Hepatic Cellular Senescence by Suppressing the MAPK/NF-κB Signaling Pathway in Aged Mice

by Da-Yeon Lee, Su-Jeong Lee, Prabha Chandrasekaran, Gopal Lamichhane, Jennifer F. O’Connell, Josephine M. Egan and Yoo Kim

Antioxidants 2023, 12(6), 1165; https://doi.org/10.3390/antiox12061165 - 27 May 2023

Cited by 5 | Viewed by 2072

Abstract

Dietary interventions with bioactive compounds have been found to suppress the accumulation of senescent cells and senescence-associated secretory phenotypes (SASPs). One such compound, curcumin (CUR), has beneficial health and biological effects, including antioxidant and anti-inflammatory properties, but its ability to prevent hepatic cellular senescence is unclear. The objective of this study was to investigate the effects of dietary CUR as an antioxidant on hepatic cellular senescence and determine its benefits on aged mice. We screened the hepatic transcriptome and found that CUR supplementation led to the downregulation of senescence-associated hepatic gene expressions in both usually fed and nutritionally challenged aged mice. Our results showed that CUR supplementation enhanced antioxidant properties and suppressed mitogen-activated protein kinase (MAPK) signaling cascades in the liver, particularly c-Jun N-terminal kinase (JNK) in aged mice and p38 in diet-induced obese aged mice. Furthermore, dietary CUR decreased the phosphorylation of nuclear factor-κB (NF-κB), a downstream transcription factor of JNK and p38, and inhibited the mRNA expression of proinflammatory cytokines and SASPs. The potency of CUR administration was demonstrated in aged mice via enhanced insulin homeostasis along with declined body weight. Taken together, these results suggest that CUR supplementation may be a nutritional strategy to prevent hepatic cellular senescence. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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14 pages, 4958 KiB

Open AccessArticle

Effects of Particle Size of Curcumin Solid Dispersions on Bioavailability and Anti-Inflammatory Activities

by Chihiro Kato, Mayuko Itaya-Takahashi, Taiki Miyazawa, Junya Ito, Isabella Supardi Parida, Hiroki Yamada, Akari Abe, Mika Shibata, Keita Someya and Kiyotaka Nakagawa

Antioxidants 2023, 12(3), 724; https://doi.org/10.3390/antiox12030724 - 15 Mar 2023

Cited by 2 | Viewed by 1722

Abstract

The delivery of curcumin (CUR) using the solid dispersion system (CUR solid dispersions; C-SDs) has been shown to improve CUR bioavailability. However, it is unclear how different particle sizes of C-SDs affect the bioavailability and biological activities of CUR. Hence, we prepared C-SDs in different sizes using food-grade excipients and evaluated their bioavailability and biological activities. By pulverizing large particle sizes of C-SDs using zirconia beads, we successfully prepared C-SDs I-IV (particle size: (I) 120, (II) 447, (III) 987, (IV) 1910 nm). When administrated orally in rats, the bioavailability of CUR was increased with decreasing C-SDs size, most likely by improving its solubility in micelles. When administrated intravenously in rats, blood concentrations of CUR were increased with increasing particle size, suggesting that larger C-SDs presumably control the metabolic conversion of CUR. In RAW264 cells, more CUR was taken up by cells as their sizes reduced, and the more potent their anti-inflammatory activities were, suggesting that smaller C-SDs were taken up through a number of cellular uptake pathways. Altogether, the present study showed an evident effect of C-SDs size on their bioavailability and anti-inflammatory activities—information that serves as a basis for improving the functionality of CUR. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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21 pages, 4639 KiB

Open AccessArticle

Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial β-Oxidation and Lipid Metabolism in Kidney and Liver

by Zeltzin Alejandra Ceja-Galicia, Fernando Enrique García-Arroyo, Omar Emiliano Aparicio-Trejo, Mohammed El-Hafidi, Guillermo Gonzaga-Sánchez, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Martha Guevara-Cruz, Armando R. Tovar, Pedro Rojas-Morales, Ana Karina Aranda-Rivera, Laura Gabriela Sánchez-Lozada, Edilia Tapia and José Pedraza-Chaverri

Antioxidants 2022, 11(11), 2195; https://doi.org/10.3390/antiox11112195 - 06 Nov 2022

Cited by 6 | Viewed by 2018

Abstract

Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR’s potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and β-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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Review

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26 pages, 1400 KiB

Open AccessReview

Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment

by Caroline Bertoncini-Silva, Adelina Vlad, Roberta Ricciarelli, Priscila Giacomo Fassini, Vivian Marques Miguel Suen and Jean-Marc Zingg

Antioxidants 2024, 13(3), 331; https://doi.org/10.3390/antiox13030331 - 08 Mar 2024

Viewed by 3059

Abstract

Curcumin, a natural polyphenolic component from Curcuma longa roots, is the main bioactive component of turmeric spice and has gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity. While intake from dietary sources such as curry may be sufficient to affect the intestinal microbiome and thus may act indirectly, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10–20 microM). Several strategies can be envisioned to increase curcumin levels in the body, such as decreasing its metabolism or increasing absorption through the formation of nanoparticles. However, since high curcumin levels could also lead to undesired regulatory effects on cellular signaling and gene expression, such studies may need to be carefully monitored. Here, we review the bioavailability of curcumin and to what extent increasing curcumin levels using nanoformulations may increase the bioavailability and bioactivity of curcumin and its metabolites. This enhancement could potentially amplify the disease-preventing effects of curcumin, often by leveraging its robust antioxidant properties. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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18 pages, 1113 KiB

Open AccessReview

Dual Action of Curcumin as an Anti- and Pro-Oxidant from a Biophysical Perspective

by Agnieszka Wolnicka-Glubisz and Anna Wisniewska-Becker

Antioxidants 2023, 12(9), 1725; https://doi.org/10.3390/antiox12091725 - 06 Sep 2023

Cited by 5 | Viewed by 1553

Abstract

Curcumin, a natural polyphenol widely used as a spice, colorant and food additive, has been shown to have therapeutic effects against different disorders, mostly due to its anti-oxidant properties. Curcumin also reduces the efficiency of melanin synthesis and affects cell membranes. However, curcumin can act as a pro-oxidant when blue light is applied, since upon illumination it can generate singlet oxygen. Our review aims to describe this dual role of curcumin from a biophysical perspective, bearing in mind its concentration, bioavailability-enhancing modifications and membrane interactions, as well as environmental conditions such as light. In low concentrations and without irradiation, curcumin shows positive effects and can be recommended as a beneficial food supplement. On the other hand, when used in excess or irradiated, curcumin can be toxic. Therefore, numerous attempts have been undertaken to test curcumin as a potential photosensitizer in photodynamic therapy (PDT). At that point, we underline that curcumin-based PDT is limited to the treatment of superficial tumors or skin and oral infections due to the weak penetration of blue light. Additionally, we conclude that an increase in curcumin bioavailability through the using nanocarriers, and therefore its concentration, as well as its topical use if skin is exposed to light, may be dangerous. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin)

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