PMID: 

Eur J Pharm Biopharm. 2019 Nov ;144:154-164. Epub 2019 Sep 19. PMID: 31542438

Abstract Title: 

Liposomes augment biological benefits of curcumin for multitargeted skin therapy.

Abstract: 

Curcumin, a multi-targeting pharmacologically active compound, is a promising molecule for the treatment of skin inflammation and infection in chronic wounds. However, its hydrophobic nature remains to be a challenge in development of its pharmaceutical products, including dermatopharmaceuticals. Here we propose deformable liposomes (DLs) as a mean to overcome the curcumin limitations in skin treatment. We explored the properties and biological effects of curcumin containing DLs (curcumin-DLs) with varying surface charge by preparing the neutral (NDLs), cationic (CDLs) and anionic (ADLs) nanocarriers. The vesicles of mean diameter 200-300 nm incorporated high curcumin load mirroring the type of employed surfactant. Curcumin-CDLs provided the most sustained ex vivo penetration of curcumin through the full thickness human skin. Although the curcumin-CDLs were the most potent regarding the in vitro anti-inflammatory activity, all curcumin-DLs were superior to curcumin in solution (control). No cytotoxicity in human skin fibroblasts was detected. All DLs significantly inhibited bacterial Staphylococcus aureus and Streptococcus pyogenes growth in vitro. The curcumin-CDLs were found superior to other DLs. The incorporation of curcumin in DLs enabled both its sustained skin penetration and enhancement of its biological properties. Cationic nanocarriers enhanced the activities of curcumin to the greatest extent.

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PMID: 

J Liposome Res. 2019 Nov 12:1-10. Epub 2019 Nov 12. PMID: 31631726

Abstract Title: 

Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin.

Abstract: 

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution ofDOX, limiting its side effects, via CURC-dependent antioxidant effects.

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PMID: 

Anticancer Res. 2019 Mar ;39(3):1161-1168. PMID: 30842145

Abstract Title: 

Intense Uptake of Liposomal Curcumin by Multiple Myeloma Cell Lines: Comparison to Normal Lymphocytes, Red Blood Cells and Chronic Lymphocytic Leukemia Cells.

Abstract: 

BACKGROUND/AIM: Curcumin is being widely investigated for its anticancer properties and several studies in the literature suggest that curcumin is distributed to a higher degree in cancer cells compared to normal cells. The goal of this study was to investigate the disposition of curcumin in the form of Lipocurc™ in multiple myeloma (MM)-causing plasma cell lines and B-lymphocytes from healthy individuals and compare the uptake to previously published data for red blood cells (RBCs), peripheral blood mononuclear cells (PBMCs) from healthy individuals and PBMCs from patients with chronic lymphocytic leukemia (CLL-cells).MATERIALS AND METHODS: Two MM-producing cell lines were studied: RPMI-8266, an IgG lambda cell line, and NCL-H929, an IgA kappa line. The distribution of liposomal curcumin and its metabolism to the major stable metabolite tetrahydrocurcumin (THC) were measured in vitro in the cell lines and B-lymphocytes. The cells were incubated in plasma protein-supplemented media with liposomal curcumin (Lipocurc™) for 15 min at 37°C and the levels of curcumin and THC in cells and medium were determined by liquid chromatography tandem mass spectrometry.RESULTS: Extremely intense uptake was seen in both MM lines compared to that in B-lymphocytes and previously published data in RBCs, PBMCs and CLL cells. The levels of curcumin in RPMI-8266 and NCI-H929 cells were 14,225±847 and 12,723±500 pg/10cells compared to 19±5,587±86 and 3,122±166 pg/10cells in RBCs, PBMCs and CLL cells, respectively. Conversion of curcumin to THC was greatest in PBMCs, considerably less in CLL cells and minimal or absent in B-lymphocytes and MM cell lines.CONCLUSION: The extremely intense uptake of curcumin (as Lipocurc™) in both MM lines further suggests that Lipocurc™ should be investigated in the treatment of patients with this disease.

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PMID: 

Exp Ther Med. 2019 Nov ;18(5):3681-3687. Epub 2019 Sep 5. PMID: 31602247

Abstract Title: 

Tetrahydrocurcumin protects against spinal cord injury and inhibits the oxidative stress response by regulating FOXO4 in model rats.

Abstract: 

It has been reported that tetrahydrocurcumin has hypoglycemic, hypolipidemic, anti-metastasis, anticancer and anti-depressant pharmacological effects, and its antioxidative, hypoglycemic and hypolipidemic properties are better than those of curcumin. The present study assessed whether tetrahydrocurcumin exerts a neuroprotective effect against spinal cord injury (SCI) and investigated the underlying mechanisms. In a rat model of SCI, tetrahydrocurcumin enhanced the average Basso-Beattie-Bresnahan scores, inhibited water accumulation in the spinal cord and decreased inflammatory factors. Furthermore, oxidative stress and apoptosis (caspase-3 activity and B-cell lymphoma 2-associated X protein levels) were also suppressed in SCI rats treated with tetrahydrocurcumin. Tetrahydrocurcumin effectively decreased the gene expression of matrix metalloproteinase-3 and -13, as well as cyclooxygenase-2, promoted the phosphorylation of Akt and enhanced the protein expression of forkhead box (FOX)O4 in SCI rats. The present study delineates that tetrahydrocurcumin protects against SCI and inhibits the oxidative stress response by regulating the FOXO4 in SCI model rats.

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PMID: 

Cancer Manag Res. 2019 ;11:6829-6840. Epub 2019 Jul 24. PMID: 31440081

Abstract Title: 

MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin.

Abstract: 

The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis.The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC.qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot.miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment. Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.

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PMID: 

Med Sci Monit. 2019 Oct 4 ;25:7451-7458. Epub 2019 Oct 4. PMID: 31584928

Abstract Title: 

Curcumin Inhibits Cell Viability and Increases Apoptosis of SW620 Human Colon Adenocarcinoma Cells via the Caudal Type Homeobox-2 (CDX2)/Wnt/β-Catenin Pathway.

Abstract: 

BACKGROUND Curcumin is a polyphenol compound extracted from the root of the herb Curcuma longa, which is used in traditional Chinese medicine (TCM). Worldwide, colorectal carcinoma (CRC) is an increasing cause of morbidity and mortality. This study aimed to investigate the effects of increasing concentrations of curcumin on cell viability, proliferation, and apoptosis of SW620 human colonic adenocarcinoma cells cultured in vitro, and the signaling pathways involved. MATERIAL AND METHODS SW620 human colonic adenocarcinoma cells were cultured in curcumin at concentrations of 0, 4, 8, 16, and 32μmol/l for 48 hours. Specific small interfering RNA (siRNA) was transfected into SW620 cells to silence the expression of caudal type homeobox-2 (CDX2). Cell viability was measured using the MTT assay. Flow cytometry evaluated cell apoptosis. Western blot and reverse transcriptase-polymerase chainreaction (RT-PCR) were used to assess the nuclear translocation of b-catenin and the activation of Wnt signaling. RESULTS Curcumin reduced cell viability and increased apoptosis of SW620 human colonic adenocarcinoma cells in a dose-dependent way, and increased the expression of CDX2 but decreased ß-catenin nuclear translocation and the expression of Wnt3a, c-Myc, survivin, and cyclin D1. CDX2 silencing significantly reduced the effects of curcumin on SW620 human colonic adenocarcinoma cells. The nuclear translocation of ß-catenin, and expression levels of Wnt3a, c-Myc, survivin, and cyclin D1 were significantly higher in CDX2-silenced SW620 cells. CONCLUSIONS Curcumin reduced cell viability and increased apoptosis in SW620 human colonic adenocarcinoma cells by restoring CDX2, which inhibited the Wnt/ß-catenin signaling pathway.

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PMID: 

Curr Drug Metab. 2019 Oct 7. Epub 2019 Oct 7. PMID: 31589120

Abstract Title: 

Curcumin – A Novel Therapeutic Agent In The Prevention Of Colorectal Cancer.

Abstract: 

BACKGROUND: Colorectal cancer is the third important cause of cancer-associated deaths across the world. Hence, there is an urgent need for understanding complete mechanism associated with colorectal cancer, which in turn can be utilised toward early detection as well as treatment of colorectal cancer in human. Though colorectal cancer is a complex process and chemotherapy is the first step toward the treatment of colorectal cancer, recently several studies suggested that dietary phytochemicals may also aid significantly in reducing colorectal cancer risk in human. However, only few phytochemicals, specifically curcumin derived from the rhizomes of Curcuma longa, have better chemotherapeutic property, which might be because of its ability to regulate the activity of key factors associated with the initiation, promotion, as well as progression of tumours.OBJECTIVES: In the present review, the authors made an attempt to summarize the physiochemical properties of curcumin, which in turn prevent colorectal cancer via regulating numerous cell signalling as well as genetic pathways.CONCLUSIONS: Accumulated evidence suggested that curcumin suppresses tumour/colon cancer through various ways, (a) restricting cell cycle progression, or stimulating apoptosis, (b) restricting angiogenesis, anti-apoptotic proteins expression, cell survival signalling pathways&their cross-communication and (c) regulating immune responses. The information discussed in the present review will be useful in the drug discovery process as well as the treatment and prevention of colorectal cancer in human.

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PMID: 

Curr Mol Med. 2019 Oct 16. Epub 2019 Oct 16. PMID: 31622191

Abstract Title: 

Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury.

Abstract: 

Curcumin is a naturally occurring polyphenol which is isolated from the rhizome of Curcuma longa (turmeric). This medicinal compound has different biological activities including antioxidant, antibacterial, antineoplastic, and anti-inflammation. It has also therapeutic effects for cancer, neurodegenerative disorders, renal disorders, and diabetes mellitus. Curcumin is safe and well-tolerated at high concentrations without making toxicity. In the present review, we demonstrated curcumin affects the Nrf2 signaling pathway to exert its therapeutic and biological activities.

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PMID: 

Nutrients. 2019 Oct 17 ;11(10). Epub 2019 Oct 17. PMID: 31627369

Abstract Title: 

Curcumin as a Therapeutic Strategy in Liver Diseases.

Abstract: 

Liver diseases are classified as acute and chronic hepatic failures. In particular, chronic pathologies are the most common diseases in the World. Chronic pathologies of liver disease are the most common diseases in the world. There are many causes that induce a progressive and irreversible degeneration of the hepatic parenchyma, but, in general, they lead to the destruction of the normal balance between reactive oxygen stress (ROS) formation and ROS degradation within the liver. The prevalence of disabling diseases, including the hepatic diseases, is increasingly widespread, and it is important to find a safe, inexpensive, accessible and effective way to face this condition. Many recent studies have focused on different natural antioxidants, which could restore the physiological hepatic environment, thereby allowing the normal functioning of this organ. Natural products have been used to discover new leads for treating several diseases; among them, it is important to emphasize curcumin, which is a polyphenol obtained fromLinn, a plant naturally found throughout tropical and subtropical regions of the world.

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PMID: 

J Proteomics. 2018 06 30 ;182:1-11. Epub 2018 Apr 22. PMID: 29684682

Abstract Title: 

Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

Abstract: 

: Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition.SIGNIFICANCE: Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions through affinity chromatography approach coupled with mass spectrometry, has been conventionally used to identify target proteins and has yielded good results. Curcumol, has shown effective inhibition on Nasopharyngeal Carcinoma (NPC) Cells, interacted with NCL and then initiated the anti-tumor biological effect. This research demonstrated the effectiveness of chemical proteomics approaches in natural drugs molecular target identification, revealing and understanding of the novel mechanism of actions of curcumol is crucial for cancer prevention and treatment in nasopharynx cancer.

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