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Special Issue "Curcumin in Health and Disease: New Knowledge"

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 (31 July 2020).

Special Issue Editor

Prof. Dr. Beatrice E. Bachmeier
E-Mail Website
Guest Editor
Competence Center for Complementary Medicine and Naturopathy, Technical University, 80801 Munich, Germany
Interests: molecular oncology; prevention; curcumin; biomolecular research; cellular biology; plant derived bioactives; biomarkers
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Special Issue Information

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 edition, we would like to add more results and new insights from recent research projects.

Prof. Dr. Beatrice E. Bachmeier
Guest Editor

Manuscript Submission Information

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Keywords

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

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Published Papers (19 papers)

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Open AccessArticle
Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson’s Disease is Mediated by α7-Nicotinic Receptors
Int. J. Mol. Sci. 2020, 21(19), 7329; https://doi.org/10.3390/ijms21197329 - 03 Oct 2020
Cited by 1 | Viewed by 616
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic [...] Read more.
Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action against TNBC and Exhibits Synergism with Paclitaxel
Int. J. Mol. Sci. 2020, 21(16), 5777; https://doi.org/10.3390/ijms21165777 - 12 Aug 2020
Cited by 1 | Viewed by 625
Abstract
Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other [...] Read more.
Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that it decreased the cell survival and colony formation of MDA-MB-231 and MDA-MB-468 cells. An increase in mitochondrial reactive oxygen species was also observed in TNBC cells exposed to KY-20-22. Furthermore, KY-20-22 decreased epithelial–mesenchymal formation (EMT) as evidenced by the modulation of the EMT markers E-cadherin and N-cadherin. Based on the fact that KY-20-22 regulates interleukin-6, a cytokine involved in chemotherapy resistance, we combined it with paclitaxel and found that it synergistically induced anti-proliferative action in TNBC cells. The results from this study suggested that 1-chromonyl-5-imidazolylpentadienone KY-20-22 exhibited anti-cancer action in MDA-MB-231 and MDA-MB-468 cells. Future studies are required to evaluate the anti-cancer ability and bioavailability of KY-20-22 in the TNBC animal model. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/FGT Glioblastoma-Bearing Rat Model
Int. J. Mol. Sci. 2020, 21(12), 4385; https://doi.org/10.3390/ijms21124385 - 19 Jun 2020
Cited by 1 | Viewed by 633
Abstract
Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. [...] Read more.
Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Stealth Magnetoliposomes Based on Calcium-Substituted Magnesium Ferrite Nanoparticles for Curcumin Transport and Release
Int. J. Mol. Sci. 2020, 21(10), 3641; https://doi.org/10.3390/ijms21103641 - 21 May 2020
Cited by 6 | Viewed by 837
Abstract
Despite the promising pharmacological properties of curcumin, the transport and effective release of curcumin is still a challenge. The advances in functionalized nanocarriers for curcumin have also been motivated by the anticancer activity of this natural compound, aiming at targeted therapies. Here, stealth [...] Read more.
Despite the promising pharmacological properties of curcumin, the transport and effective release of curcumin is still a challenge. The advances in functionalized nanocarriers for curcumin have also been motivated by the anticancer activity of this natural compound, aiming at targeted therapies. Here, stealth (aqueous and solid) magnetoliposomes containing calcium-substituted magnesium ferrite nanoparticles, CaxMg1−xFe2O4 (with x = 0.25, 0.50, 0.75) were developed as nanocarriers for curcumin. The magnetic nanoparticles exhibit superparamagnetic properties and crystalline structure, with sizes below 10 nm. The magnetoliposomes based on these nanoparticles have hydrodynamic diameters around or below 150 nm and a low polydispersity. The influence of an alternating magnetic field (AMF) on drug release over time was evaluated and compared with curcumin release by diffusion. The results suggest the potential of drug-loaded magnetoliposomes as nanocarriers that can be magnetically guided to the tumor sites and act as agents for a synergistic effect combining magnetic hyperthermia and controlled drug release. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells
Int. J. Mol. Sci. 2020, 21(8), 2761; https://doi.org/10.3390/ijms21082761 - 16 Apr 2020
Cited by 5 | Viewed by 743
Abstract
Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most [...] Read more.
Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Curcumin Attenuates Both Acute and Chronic Immune Nephritis
Int. J. Mol. Sci. 2020, 21(5), 1745; https://doi.org/10.3390/ijms21051745 - 04 Mar 2020
Cited by 5 | Viewed by 1268
Abstract
Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney [...] Read more.
Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney Injury, AKI) and murine lupus model (representing chronic kidney disease, CKD). In the AKI model, female anti-GBM 129/svj mice were administered with curcumin right before disease induction. In the CKD model, female MRL.lpr mice at the age of 8-10 weeks old were treated with curcumin or placebo via oral gavage daily for two months. After treatment, serum autoantibody levels, splenomegaly and spleen cellularity were reduced in murine lupus. Collectively, curcumin ameliorated kidney disease in the two mouse models with either acute or chronic nephritis, as marked by reduced proteinuria, blood urea nitrogen, glomerulonephritis, crescent formation, tubule-interstitial disease, and renal infiltration by lymphocytes. In addition, curcumin treatment reduced activation of the NFkB, MAPK, AKT and pBAD pathways either systemically, or within the inflamed kidneys. These findings suggest that natural food supplements could become an alternative approach to ameliorating immune-mediated kidney diseases. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin
Int. J. Mol. Sci. 2020, 21(5), 1661; https://doi.org/10.3390/ijms21051661 - 28 Feb 2020
Cited by 2 | Viewed by 1502
Abstract
In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been [...] Read more.
In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
A Curcumin Derivative Activates TFEB and Protects Against Parkinsonian Neurotoxicity in Vitro
Int. J. Mol. Sci. 2020, 21(4), 1515; https://doi.org/10.3390/ijms21041515 - 22 Feb 2020
Cited by 5 | Viewed by 1430
Abstract
TFEB (transcription factor EB), which is a master regulator of autophagy and lysosome biogenesis, is considered to be a new therapeutic target for Parkinson’s disease (PD). However, only several small-molecule TFEB activators have been discovered and their neuroprotective effects in PD are unclear. [...] Read more.
TFEB (transcription factor EB), which is a master regulator of autophagy and lysosome biogenesis, is considered to be a new therapeutic target for Parkinson’s disease (PD). However, only several small-molecule TFEB activators have been discovered and their neuroprotective effects in PD are unclear. In this study, a curcumin derivative, named E4, was identified as a potent TFEB activator. Compound E4 promoted the translocation of TFEB from cytoplasm into nucleus, accompanied by enhanced autophagy and lysosomal biogenesis. Moreover, TFEB knockdown effectively attenuated E4-induced autophagy and lysosomal biogenesis. Mechanistically, E4-induced TFEB activation is mainly through AKT-MTORC1 inhibition. In the PD cell models, E4 promoted the degradation of α-synuclein and protected against the cytotoxicity of MPP+ (1-methyl-4-phenylpyridinium ion) in neuronal cells. Overall, the TFEB activator E4 deserves further study in animal models of neurodegenerative diseases, including PD. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa
Int. J. Mol. Sci. 2020, 21(1), 337; https://doi.org/10.3390/ijms21010337 - 04 Jan 2020
Cited by 9 | Viewed by 4095
Abstract
Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production [...] Read more.
Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-α) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Curcumin Ameliorates Benzo[a]pyrene-Induced DNA Damages in Stomach Tissues of Sprague-Dawley Rats
Int. J. Mol. Sci. 2019, 20(22), 5533; https://doi.org/10.3390/ijms20225533 - 06 Nov 2019
Cited by 8 | Viewed by 910
Abstract
Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated [...] Read more.
Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of curcumin on BaP-induced DNA damage in rat stomach tissues. BaP (20 mg/kg/day) and curcumin (50, 100, or 200 mg/kg) were administered daily to Sprague-Dawley rats by oral gavage over 30 days. Curcumin was pre-administered before BaP exposure. All rats were euthanized, and liver, kidney, and stomach tissues were removed at 24 h after the last treatment. We observed that aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose levels were significantly reduced in rats treated with high dose co-administration of curcumin (200 mg/kg) compared to BaP alone. The expression levels of cytochrome P450 (CYP) 1A1 and CYP1B1 were significantly increased in the liver of rats treated with BaP. However, co-administration of curcumin (200 mg/kg) with BaP markedly reduced CYP1A1 expression in a dose-dependent manner. Furthermore, plasma levels of BaP-diolepoxide (BPDE) and BaP metabolites were significantly reduced by co-administration of curcumin (200 mg/kg). Additionally, co-administration of curcumin (200 mg/kg) with BaP significantly reduced the formation of BPDE-I-DNA and 8-hydroxydeoxy guanosine (8-OHdG) adducts in the liver, kidney, and stomach tissues. The inhibition of these adduct formations were more prominent in the stomach tissues than in the liver. Overall, our observations suggest that curcumin might inhibit BaP-induced gastrointestinal tumorigenesis and shows promise as a chemopreventive agent. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessArticle
Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway
Int. J. Mol. Sci. 2019, 20(18), 4606; https://doi.org/10.3390/ijms20184606 - 17 Sep 2019
Cited by 10 | Viewed by 1870
Abstract
Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent [...] Read more.
Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/mL of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1–100 µg/mL of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock onto the active sites of CYP17A1, CYP19A1, as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies suggest that curcuminoids may cause inhibition of steroid metabolism, especially at higher dosages. Also, the recent popularity of turmeric powder as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. The molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Review

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Open AccessReview
Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma
Int. J. Mol. Sci. 2020, 21(19), 7150; https://doi.org/10.3390/ijms21197150 - 28 Sep 2020
Viewed by 763
Abstract
Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human [...] Read more.
Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
Open AccessReview
Curcumin—A Viable Agent for Better Bladder Cancer Treatment
Int. J. Mol. Sci. 2020, 21(11), 3761; https://doi.org/10.3390/ijms21113761 - 26 May 2020
Cited by 3 | Viewed by 981
Abstract
Although the therapeutic armamentarium for bladder cancer has considerably widened in the last few years, severe side effects and the development of resistance hamper long-term treatment success. Thus, patients turn to natural plant products as alternative or complementary therapeutic options. One of these [...] Read more.
Although the therapeutic armamentarium for bladder cancer has considerably widened in the last few years, severe side effects and the development of resistance hamper long-term treatment success. Thus, patients turn to natural plant products as alternative or complementary therapeutic options. One of these is curcumin, the principal component of Curcuma longa that has shown chemopreventive effects in experimental cancer models. Clinical and preclinical studies point to its role as a chemosensitizer, and it has been shown to protect organs from toxicity induced by chemotherapy. These properties indicate that curcumin could hold promise as a candidate for additive cancer treatment. This review evaluates the relevance of curcumin as an integral part of therapy for bladder cancer. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessReview
Curcumin and Endometriosis
Int. J. Mol. Sci. 2020, 21(7), 2440; https://doi.org/10.3390/ijms21072440 - 31 Mar 2020
Cited by 6 | Viewed by 1993
Abstract
Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, [...] Read more.
Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, an imbalance between reactive oxygen species and antioxidants, could have a key role in the initiation and progression of endometriosis by resulting in inflammatory responses in the peritoneal cavity. Nevertheless, the mechanisms underlying this disease are still unclear and therapies are not currently efficient. Curcumin is a major anti-inflammatory agent. Several findings have highlighted the anti-oxidant, anti-inflammatory and anti-angiogenic properties of curcumin. The purpose of this review is to summarize the potential action of curcumin in endometriosis by acting on inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
Open AccessReview
Curcumin and Colorectal Cancer: From Basic to Clinical Evidences
Int. J. Mol. Sci. 2020, 21(7), 2364; https://doi.org/10.3390/ijms21072364 - 29 Mar 2020
Cited by 14 | Viewed by 2028
Abstract
Curcumin diffuses through cell membranes into the endoplasmic reticulum, mitochondria, and nucleus, where it exerts actions, as an antioxidant property. Therefore, its use has been advocated for chemopreventive, antimetastatic, and anti-angiogenic purposes. We conducted a literature review to summarize studies investigating the relationship [...] Read more.
Curcumin diffuses through cell membranes into the endoplasmic reticulum, mitochondria, and nucleus, where it exerts actions, as an antioxidant property. Therefore, its use has been advocated for chemopreventive, antimetastatic, and anti-angiogenic purposes. We conducted a literature review to summarize studies investigating the relationship between curcumin and colorectal cancer (CRC). In vitro studies, performed on human colon cancer cell lines, showed that curcumin inhibited cellular growth through cycle arrest at the G2/M and G1 phases, as well as stimulated apoptosis by interacting with multiple molecular targets. In vivo studies have been performed in inflammatory and genetic CRC animal models with a chemopreventive effect. To improve curcumin bioavailability, it has been associated with small particles that increase its absorption when orally administered with excellent results on both inflammation and carcinogenesis. Curcumin has been used, moreover, as a component of dietetic formulations for CRC chemoprevention. These combinations showed in vitro and in vivo anticarcinogenetic properties in inflammation-related and genetic CRC. A synergic effect was suggested using an individual constituent dosage, which was lower than that experimentally used “in vivo” for single components. In conclusion, curcumin falls within the category of plant origin substances able to prevent CRC in animals. This property offers promising expectations in humans. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessReview
The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties
Int. J. Mol. Sci. 2020, 21(7), 2299; https://doi.org/10.3390/ijms21072299 - 26 Mar 2020
Cited by 10 | Viewed by 1214
Abstract
Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell [...] Read more.
Natural products have been used in medicine for thousands of years. Given their potential health benefits, they have gained significant popularity in recent times. The administration of phytochemicals existed shown to regulate differential gene expression and modulate various cellular pathways implicated in cell protection. Curcumin is a natural dietary polyphenol extracted from Curcuma Longa Linn with different biological and pharmacological effects. One of the important targets of curcumin is Toll-like receptor-4 (TLR-4), the receptor which plays a key role in the modulation of the immune responses and the stimulation of inflammatory chemokines and cytokines production. Different studies have demonstrated that curcumin attenuates inflammatory response via TLR-4 acting directly on receptor, or by its downstream pathway. Curcumin bioavailability is low, so the use of exosomes, as nano drug delivery, could improve the efficacy of curcumin in inflammatory diseases. The focus of this review is to explore the therapeutic effect of curcumin interacting with TLR-4 receptor and how this modulation could improve the prognosis of neuroinflammatory and rheumatic diseases. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessReview
Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids
Int. J. Mol. Sci. 2020, 21(6), 1975; https://doi.org/10.3390/ijms21061975 - 13 Mar 2020
Cited by 13 | Viewed by 1834
Abstract
Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly [...] Read more.
Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessReview
Mutual Two-Way Interactions of Curcumin and Gut Microbiota
Int. J. Mol. Sci. 2020, 21(3), 1055; https://doi.org/10.3390/ijms21031055 - 05 Feb 2020
Cited by 11 | Viewed by 2703
Abstract
Curcumin, an herbal naturally occurring polyphenol, has recently been proposed for the treatment of neurodegenerative, neurological and cancer diseases due to its pleiotropic effect. Recent studies indicated that dysbiosis is associated with the abovementioned and other diseases, and gut microflora may be a [...] Read more.
Curcumin, an herbal naturally occurring polyphenol, has recently been proposed for the treatment of neurodegenerative, neurological and cancer diseases due to its pleiotropic effect. Recent studies indicated that dysbiosis is associated with the abovementioned and other diseases, and gut microflora may be a new potential therapeutic target. The new working hypothesis that could explain the curative role of curcumin, despite its limited availability, is that curcumin acts indirectly on the brain, affecting the “gut–brain–microflora axis”, a complex two-way system in which the gut microbiome and its composition, are factors that preserve and determine brain health. It is therefore suspected that curcumin and its metabolites have a direct regulatory effect on gut microflora and vice versa, which may explain the paradox between curcumin’s poor bioavailability and its commonly reported therapeutic effects. Curcumin and its metabolites can have health benefits by eliminating intestinal microflora dysbiosis. In addition, curcumin undergoes enzymatic modifications by bacteria, forming pharmacologically more active metabolites than their parent, curcumin. In this review, we summarize a number of studies that highlight the interaction between curcumin and gut microbiota and vice versa, and we consider the possibility of microbiome-targeted therapies using curcumin, particularly in disease entities currently without causal treatment. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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Open AccessReview
Substantiation for the Use of Curcumin during the Development of Neurodegeneration after Brain Ischemia
Int. J. Mol. Sci. 2020, 21(2), 517; https://doi.org/10.3390/ijms21020517 - 14 Jan 2020
Cited by 11 | Viewed by 1060
Abstract
Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review [...] Read more.
Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of curcumin influence on post-ischemic brain damage. Some data on the clinical benefits of curcumin treatment of post-ischemic brain in terms of clinical symptoms and adverse reactions have been reviewed. The data in this review contributes to a better understanding of the potential benefits of curcumin in the treatment of neurodegenerative changes after ischemia and informs scientists, clinicians, and patients, as well as their families and caregivers about the possibilities of such treatment. Due to the pleotropic properties of curcumin, including anti-amyloid, anti-tau protein hyperphosphorylation, anti-inflammatory, anti-apoptotic, and neuroprotective action, as well as increasing neuronal lifespan and promoting neurogenesis, curcumin is a promising candidate for the treatment of post-ischemic neurodegeneration with misfolded proteins accumulation. In this way, it may gain interest as a potential therapy to prevent the development of neurodegenerative changes after cerebral ischemia. In addition, it is a safe substance and inexpensive, easily accessible, and can effectively penetrate the blood–brain barrier and neuronal membranes. In conclusion, the evidence available in a review of the literature on the therapeutic potential of curcumin provides helpful insight into the potential clinical utility of curcumin in the treatment of neurological neurodegenerative diseases with misfolded proteins. Therefore, curcumin may be a promising supplementary agent against development of neurodegeneration after brain ischemia in the future. Indeed, there is a rational scientific basis for the use of curcumin for the prophylaxis and treatment of post-ischemic neurodegeneration. Full article
(This article belongs to the Special Issue Curcumin in Health and Disease: New Knowledge)
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