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Curcumin in Health and Disease 3.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 47919

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Prof. Dr. Beatrice E. Bachmeier

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Institute of Pharmaceutical Biology, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany
Interests: noncommunicable diseases; clinical and preclinical studies; real world evidence; patient reported outcomes; biomolecular research; cellular biology; plant derived bioactives; phytopharmaceuticals; biomarkers
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Dear Colleagues,

The plant-derived polyphenol Curcumin has been used in health and disease for thousands of years and its therapeutic effects have been successfully utilized in Ayurvedic and Traditional Chinese Medicine in order to treat inflammatory diseases. Current results from modern biomolecular research reveal the modulatory effects of Curcumin on a variety of signal transduction pathways associated with inflammation and cancer. In this context, anti-oxidant, anti-inflammatory, anti-tumorigenic, and even anti-metastatic activities are discussed. On the cellular level, reduced activity of several transcription factors, such as NFkB or AP-1 and suppression of inflammatory cytokines, matrix degrading enzymes, metastasis related genes and even microRNAs are reported. On functional levels, these molecular effects translate into reduced proliferative, invasive and metastatic capacity, as well as induced tumor cell apoptosis. All these effects have been observed not only in vitro but also in animal models. In combination with anti-neoplastic drugs like taxols or kinase inhibitors or radiation therapy, Curcumin potentiates their therapeuthic power and shows even protective effects against undesired side effects.

Natural plant-derived compounds like Curcumin have one significant advantage: They largely do not exert side effects. This feature qualifies Curcumin for primary prevention, in healthy persons with a predisposition to cancer, arteriosclerosis or chronic inflammatory dieseases. Nonetheless, Curcumin is considered "safe", however, toxic effects especially concerning high dosages, long-term intake and pharmacological interactions with other compounds have to be tested.

This Special Issue examines in detail, and provides an update on, the molecular targets, protective effects, and modes of action of natural plant-derived compounds and their roles in the prevention and treatment of human diseases.

Due to the success of the first and second editions, we would like to add more results and new insights from recent research projects.

https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/curcumin_health

https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/curcumin_health_new

Prof. Dr. Beatrice Bachmeier
Guest Editor

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Keywords

Curcumin
natural compounds
bioactives
biomarkers
molecular pathways
cancer
inflammation
prevention
combination therapy
toxicity/safety

Related Special Issue

Curcumin in Health and Disease 4.0 in International Journal of Molecular Sciences (5 articles)

Published Papers (10 papers)

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Editorial

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4 pages, 202 KiB

Open AccessEditorial

Curcumin 3.0—Therapeutic and Diagnostic Potential in Cancer and Beyond

by Beatrice E. Bachmeier and Roman Blaheta

Int. J. Mol. Sci. 2022, 23(10), 5398; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105398 - 12 May 2022

Cited by 1 | Viewed by 1212

Abstract

Curcumin is one of the most interesting plant-derived polyphenols with a high potential for therapeutic, and even diagnostic, application in various diseases [...] Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

Research

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18 pages, 3246 KiB

Open AccessArticle

In Silico and In Vitro Screening of 50 Curcumin Compounds as EGFR and NF-κB Inhibitors

by Mohamed E. M. Saeed, Rümeysa Yücer, Mona Dawood, Mohamed-Elamir F. Hegazy, Assia Drif, Edna Ooko, Onat Kadioglu, Ean-Jeong Seo, Fadhil S. Kamounah, Salam J. Titinchi, Beatrice Bachmeier and Thomas Efferth

Int. J. Mol. Sci. 2022, 23(7), 3966; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073966 - 02 Apr 2022

Cited by 14 | Viewed by 3332

Abstract

The improvement of cancer chemotherapy remains a major challenge, and thus new drugs are urgently required to develop new treatment regimes. Curcumin, a polyphenolic antioxidant derived from the rhizome of turmeric (Curcuma longa L.), has undergone extensive preclinical investigations and, thereby, displayed remarkable efficacy in vitro and in vivo against cancer and other disorders. However, pharmacological limitations of curcumin stimulated the synthesis of numerous novel curcumin analogs, which need to be evaluated for their therapeutic potential. In the present study, we calculated the binding affinities of 50 curcumin derivatives to known cancer-related target proteins of curcumin, i.e., epidermal growth factor receptor (EGFR) and nuclear factor κB (NF-κB) by using a molecular docking approach. The binding energies for EGFR were in a range of −12.12 (±0.21) to −7.34 (±0.07) kcal/mol and those for NF-κB ranged from −12.97 (±0.47) to −6.24 (±0.06) kcal/mol, indicating similar binding affinities of the curcumin compounds for both target proteins. The predicted receptor-ligand binding constants for EGFR and curcumin derivatives were in a range of 0.00013 (±0.00006) to 3.45 (±0.10) µM and for NF-κB in a range of 0.0004 (±0.0003) to 10.05 (±4.03) µM, indicating that the receptor-ligand binding was more stable for EGFR than for NF-κB. Twenty out of 50 curcumin compounds showed binding energies to NF-κB smaller than −10 kcal/mol, while curcumin as a lead compound revealed free binding energies of >−10 kcal/mol. Comparable data were obtained for EGFR: 15 out of 50 curcumin compounds were bound to EGFR with free binding energies of <−10 kcal/mol, while the binding affinity of curcumin itself was >−10 kcal/mol. This indicates that the derivatization of curcumin may indeed be a promising strategy to improve targe specificity and to obtain more effective anticancer drug candidates. The in silico results have been exemplarily validated using microscale thermophoresis. The bioactivity has been further investigated by using resazurin cell viability assay, lactate dehydrogenase assay, flow cytometric measurement of reactive oxygen species, and annexin V/propidium iodide assay. In conclusion, molecular docking represents a valuable approach to facilitate and speed up the identification of novel targeted curcumin-based drugs to treat cancer. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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21 pages, 7312 KiB

Open AccessArticle

Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells

by Aleksandra Majchrzak-Celińska, Robert Kleszcz, Anna Stasiłowicz-Krzemień and Judyta Cielecka-Piontek

Int. J. Mol. Sci. 2021, 22(20), 11285; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011285 - 19 Oct 2021

Cited by 13 | Viewed by 3604

Abstract

Glioblastoma (GBM) is an extremely aggressive brain tumor awaiting novel, efficient, and minimally toxic treatment. Curcuminoids (CCM), polyphenols from Curcuma longa, and sodium butyrate (NaBu), a histone deacetylase inhibitor naturally occurring in the human body, await elucidation as potential anti-GBM agents. Thus, the aim of this study was to analyze CCM and NaBu both separately and as a combination treatment using three GBM cell lines. MTT was used for cytotoxicity evaluation, and the combination index was calculated for synergism prediction. Cell cycle, apoptosis, and reactive oxygen species (ROS) generation were analyzed using flow cytometry. DNA methylation was verified by MS-HRM and mRNA expression by qPCR. The permeability through the blood-brain barrier (BBB) and through the nasal cavity was evaluated using PAMPA model. The results of this study indicate that CCM and NaBu synergistically reduce the viability of GBM cells inducing apoptosis and cell cycle arrest. These effects are mediated via ROS generation and changes in gene expression, including upregulation of Wnt/β-catenin pathway antagonists, SFRP1, and RUNX3, and downregulation of UHRF1, the key epigenetic regulator. Moreover, NaBu ameliorated CCM permeability through the BBB and the nasal cavity. We conclude that CCM and NaBu are promising agents with anti-GBM properties. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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17 pages, 3912 KiB

Open AccessArticle

Growth, Proliferation and Metastasis of Prostate Cancer Cells Is Blocked by Low-Dose Curcumin in Combination with Light Irradiation

by Jochen Rutz, Aicha Benchellal, Wajdi Kassabra, Sebastian Maxeiner, August Bernd, Stefan Kippenberger, Nadja Zöller, Felix K.-H. Chun, Eva Juengel and Roman A. Blaheta

Int. J. Mol. Sci. 2021, 22(18), 9966; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189966 - 15 Sep 2021

Cited by 14 | Viewed by 2288

Abstract

Although anti-cancer properties of the natural compound curcumin have been reported, low absorption and rapid metabolisation limit clinical use. The present study investigated whether irradiation with visible light may enhance the inhibitory effects of low-dosed curcumin on prostate cancer cell growth, proliferation, and metastasis in vitro. DU145 and PC3 cells were incubated with low-dosed curcumin (0.1–0.4 µg/mL) and subsequently irradiated with 1.65 J/cm² visible light for 5 min. Controls remained untreated and/or non-irradiated. Cell growth, proliferation, apoptosis, adhesion, and chemotaxis were evaluated, as was cell cycle regulating protein expression (CDK, Cyclins), and integrins of the α- and β-family. Curcumin or light alone did not cause any significant effects on tumor growth, proliferation, or metastasis. However, curcumin combined with light irradiation significantly suppressed tumor growth, adhesion, and migration. Phosphorylation of CDK1 decreased and expression of the counter-receptors cyclin A and B was diminished. Integrin α and β subtypes were also reduced, compared to controls. Irradiation distinctly enhances the anti-tumor potential of curcumin in vitro and may hold promise in treating prostate cancer. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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26 pages, 12314 KiB

Open AccessArticle

Lymphoid Organ Proteomes Identify Therapeutic Efficacy Biomarkers Following the Intracavitary Administration of Curcumin in a Highly Invasive Rat Model of Peritoneal Mesothelioma

by Daniel L. Pouliquen, Alice Boissard, Cécile Henry, Stéphanie Blandin, Olivier Coqueret and Catherine Guette

Int. J. Mol. Sci. 2021, 22(16), 8566; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168566 - 09 Aug 2021

Cited by 5 | Viewed by 1928

Abstract

This study aimed to identify the proteomic changes produced by curcumin treatment following stimulation of the host immune system in a rat model of malignant mesothelioma. We analyzed the proteomes of secondary lymphoid organs from four normal rats, four untreated tumor-bearing rats, and four tumor-bearing rats receiving repeated intraperitoneal administrations of curcumin. Cross-comparing proteome analyses of histological sections of the spleen from the three groups first identified a list of eighty-three biomarkers of interest, thirteen of which corresponded to proteins already reported in the literature and involved in the anticancer therapeutic effects of curcumin. In a second step, comparing these data with proteomic analyses of histological sections of mesenteric lymph nodes revealed eight common biomarkers showing a similar pattern of changes in both lymphoid organs. Additional findings included a partial reduction of the increase in spleen-circulating biomarkers, a decrease in C-reactive protein and complement C3 in the spleen and lymph nodes, and an increase in lymph node purine nucleoside phosphorylase previously associated with liver immunodeficiency. Our results suggest some protein abundance changes could be related to the systemic, distant non-target antitumor effects produced by this phytochemical. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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27 pages, 4970 KiB

Open AccessArticle

Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats

by Jelena B. Đoković, Sanela M. Savić, Jelena R. Mitrović, Ines Nikolic, Bojan D. Marković, Danijela V. Randjelović, Jelena Antic-Stankovic, Dragana Božić, Nebojša D. Cekić, Vladimir Stevanović, Bojan Batinić, Jovana Aranđelović, Miroslav M. Savić and Snežana D. Savić

Int. J. Mol. Sci. 2021, 22(15), 7991; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157991 - 27 Jul 2021

Cited by 18 | Viewed by 2480

Abstract

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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Review

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16 pages, 2552 KiB

Open AccessReview

Neuroprotective Activities of Curcumin in Parkinson’s Disease: A Review of the Literature

by Eslam El Nebrisi

Int. J. Mol. Sci. 2021, 22(20), 11248; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011248 - 18 Oct 2021

Cited by 59 | Viewed by 9079

Abstract

Parkinson’s disease (PD) is a slowly progressive multisystem disorder affecting dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is characterized by a decrease of dopamine (DA) in their striatal terminals. Treatment of PD with levodopa or DA receptor agonists replaces the function of depleted DA in the striatum. Prolonged treatment with these agents often has variable therapeutic effects and leads to the development of undesirable dyskinesia. Consequently, a crucial unmet demand in the management of Parkinson’s disease is the discovery of new approaches that could slow down, stop, or reverse the process of neurodegeneration. Novel potential treatments involving natural substances with neuroprotective activities are being developed. Curcumin is a polyphenolic compound isolated from the rhizomes of Curcuma longa (turmeric). It has been demonstrated to have potent anti-inflammatory, antioxidant, free radical scavenging, mitochondrial protecting, and iron-chelating effects, and is considered a promising therapeutic and nutraceutical agent for the treatment of PD. However, molecular and cellular mechanisms that mediate the pharmacological actions of curcumin remain largely unknown. Stimulation of nicotinic receptors and, more precisely, selective α7 nicotinic acetylcholine receptors (α7-nAChR), have been found to play a major modulatory role in the immune system via the “cholinergic anti-inflammatory pathway”. Recently, α7-nAChR has been proposed to be a potential therapeutic approach in PD. In this review, the detailed mechanisms of the neuroprotective activities of curcumin as a potential therapeutic agent to help Parkinson’s patients are being discussed and elaborated on in detail. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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19 pages, 2627 KiB

Open AccessReview

Applications of Radiolabelled Curcumin and Its Derivatives in Medicinal Chemistry

by Matteo Mari, Debora Carrozza, Erika Ferrari and Mattia Asti

Int. J. Mol. Sci. 2021, 22(14), 7410; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147410 - 10 Jul 2021

Cited by 10 | Viewed by 2391

Abstract

Curcumin is a natural occurring molecule that has aroused much interest among researchers over the years due to its pleiotropic set of biological properties. In the nuclear medicine field, radiolabelled curcumin and curcumin derivatives have been studied as potential radiotracers for the early diagnosis of Alzheimer’s disease and cancer. In the present review, the synthetic pathways, labelling methods and the preclinical investigations involving these radioactive compounds are treated. The studies entailed chemical modifications for enhancing curcumin stability, as well as its functionalisation for the labelling with several radiohalogens or metal radionuclides (fluorine-18, technetium-99m, gallium-68, etc.). Although some drawbacks have yet to be addressed, and none of the radiolabelled curcuminoids have so far achieved clinical application, the studies performed hitherto provide useful insights and lay the foundation for further developments. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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49 pages, 19240 KiB

Open AccessReview

Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

by Jeffersson Krishan Trigo-Gutierrez, Yuliana Vega-Chacón, Amanda Brandão Soares and Ewerton Garcia de Oliveira Mima

Int. J. Mol. Sci. 2021, 22(13), 7130; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137130 - 01 Jul 2021

Cited by 59 | Viewed by 8944

Abstract

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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24 pages, 1542 KiB

Open AccessReview

Metal–Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin

by Sahdeo Prasad, Dan DuBourdieu, Ajay Srivastava, Prafulla Kumar and Rajiv Lall

Int. J. Mol. Sci. 2021, 22(13), 7094; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22137094 - 30 Jun 2021

Cited by 83 | Viewed by 10590

Abstract

Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the β-diketone moiety to generate metal–curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal–curcumin complexes are discussed. Metal–curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal–curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer’s disease. These biological activities of metal–curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal–curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal–curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases. Full article

(This article belongs to the Special Issue Curcumin in Health and Disease 3.0)

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