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1.
ACS Appl Mater Interfaces ; 16(8): 9749-9767, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38359334

RESUMO

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)-chitosan (CS)/sodium alginate (SA)-Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1ß, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.


Assuntos
Anti-Infecciosos , Quitosana , Curcumina , Diabetes Mellitus , Ratos , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Curcumina/química , Antioxidantes/farmacologia , Cicatrização , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Infecciosos/farmacologia , Quitosana/farmacologia , Antibacterianos/química
2.
Diagn Pathol ; 19(1): 35, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365810

RESUMO

BACKGROUND: Breast cancer is one of the most common diseases worldwide that affects women of reproductive age. miR-221 and miR-222 are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/ß-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulating miR-221 and miR-222 expression through Wnt/ß-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. METHOD: Chitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression of miR-221 and miR-222 and Wnt/ß-catenin pathway genes was measured. RESULTS: The level of miR-221 and miR-222 and ß-catenin genes decreased in MCF-7 and MDA-MB-231 cells and WIF1 gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs and WIF1 gene expressions were increased following CC-CUR administration and ß-catenin decreased by administration of CUR. CONCLUSION: Although the composite form of curcumin decreased the expression of miR-221 and miR-222 in MCF-7 and MDA cells, with significant decreasing of ß-catenin and increasing of WIF1 gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/ß-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.


Assuntos
Neoplasias da Mama , Quitosana , Curcumina , MicroRNAs , Feminino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Quitosana/farmacologia , Curcumina/farmacologia , Células MCF-7 , MicroRNAs/metabolismo , Via de Sinalização Wnt/genética , Nanopartículas
3.
Biomed Mater ; 19(2)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38364281

RESUMO

Development of wound dressings with enhanced therapeutic properties is of great interest in the modern healthcare. In this study, a zein-based nanofibrous wound dressing containing curcumin as a therapeutic agent was fabricated through electrospinning technique. In order to achieve desirable properties, such as antibacterial characteristics, reduced contact angle, and enhanced mechanical properties, the layer-by-layer technique was used for coating the surfaces of drug-loaded nanofibers by sequentially incorporating poly (sodium 4-styrene sulfonate) as a polyanion and poly (diallyldimethylammonium chloride) (PDADMAC) as a polycation. Various analyses, including scanning electron microscopy, Fourier transform infrared spectroscopy, drug release assessment., and mechanical tests were employed to assess the characteristics of the prepared wound dressings. Based on the results, coating with polyelectrolytes enhanced the Young's modulus and tensile strength of the electrospun mat from 1.34 MPa and 4.21 MPa to 1.88 MPa and 8.83 MPa, respectively. The coating also improved the controlled release of curcumin and antioxidant activity, while the outer layer, PDADMAC, exhibited antibacterial properties. The cell viability tests proved the appropriate biocompatibility of the prepared wound dressings. Moreover, our findings show that incorporation of the coating layers enhances cell migration and provides a favorable surface for cell attachment. According to the findings of this study, the fabricated nanofibrous wound dressing can be considered a promising and effective therapeutic intervention for wound management, facilitating the healing process.


Assuntos
Curcumina , Nanofibras , Polietilenos , Compostos de Amônio Quaternário , Zeína , Nanofibras/química , Zeína/química , Bandagens/microbiologia , Antibacterianos/química
4.
Parasitol Res ; 123(2): 146, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418645

RESUMO

Leishmaniasis is a neglected disease mainly affecting low-income populations. Conventional treatment involves several side effects, is expensive, and, in addition, protozoa can develop resistance. Photodynamic therapy (PDT) is a promising alternative in treating the disease. PDT involves applying light at a specific wavelength to activate a photosensitive compound (photosensitizer, PS), to produce reactive oxygen species (ROS). Curcumin and its photochemical characteristics make it a good candidate for photodynamic therapy. Studies evaluating gene expression can help to understand the molecular events involved in the cell death caused by PDT. In the present study, RNA was extracted from promastigotes from the control and treated groups after applying PDT. RT-qPCR was performed to verify the expression of the putative ATPase beta subunit (ATPS), ATP synthase subunit A (F0F1), argininosuccinate synthase 1 (ASS), ATP-binding cassette subfamily G member 2 (ABCG2), glycoprotein 63 (GP63), superoxide dismutase (FeSODA), and glucose-6-phosphate dehydrogenase (G6PDH) genes (QR). The results suggest that PDT altered the expression of genes that participate in oxidative stress and cell death pathways, such as ATPS, FeSODA, and G6PD. The ATP-F0F1, ASS, and GP63 genes did not have their expression altered. However, it is essential to highlight that other genes may be involved in the molecular mechanisms of oxidative stress and, consequently, in the death of parasites.


Assuntos
Curcumina , Leishmania major , Fotoquimioterapia , Curcumina/farmacologia , Fotoquimioterapia/métodos , Leishmania major/genética , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Trifosfato de Adenosina , Linhagem Celular Tumoral
5.
J Enzyme Inhib Med Chem ; 39(1): 2314233, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38385332

RESUMO

The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.


Assuntos
Antineoplásicos , Curcumina , Neoplasias Gástricas , Humanos , Curcumina/farmacologia , Curcumina/química , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/química , Relação Estrutura-Atividade , Relação Quantitativa Estrutura-Atividade , Linhagem Celular Tumoral
6.
J Nanobiotechnology ; 22(1): 80, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418972

RESUMO

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.


Assuntos
Anti-Infecciosos , Curcumina , Infecção dos Ferimentos , Animais , Suínos , Hidrogéis/farmacologia , Cicatrização , Biomimética , Bandagens , Antibacterianos/uso terapêutico , Materiais Biocompatíveis , Imunoterapia , Infecção dos Ferimentos/tratamento farmacológico
7.
Appl Microbiol Biotechnol ; 108(1): 241, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413482

RESUMO

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.


Assuntos
Anti-Infecciosos , Curcumina , Antibacterianos/farmacologia , Ceftazidima/farmacologia , Curcumina/farmacologia , Curcumina/química , Azeite de Oliva/farmacologia , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Anti-Infecciosos/farmacologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana
8.
Drug Des Devel Ther ; 18: 165-192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312990

RESUMO

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.


Assuntos
Doenças Cardiovasculares , Curcumina , Cardiomiopatias Diabéticas , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Miócitos Cardíacos , Fibrose
9.
World J Gastroenterol ; 30(3): 280-282, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314128

RESUMO

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn's disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.


Assuntos
Colite Ulcerativa , Doença de Crohn , Curcumina , Doenças Inflamatórias Intestinais , Humanos , Curcumina/uso terapêutico , Qualidade de Vida , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico
10.
Mol Biol Rep ; 51(1): 261, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302805

RESUMO

BACKGROUND: The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI). METHODS AND RESULTS: Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group. CONCLUSION: Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15 days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.


Assuntos
Doença da Artéria Coronariana , Curcumina , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Infarto do Miocárdio , Isquemia Miocárdica , Ratos , Masculino , Animais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Curcumina/farmacologia , Curcumina/metabolismo , Medula Óssea/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Doença da Artéria Coronariana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células da Medula Óssea
11.
Food Res Int ; 178: 113944, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309870

RESUMO

In this study, electrospun zein/alginate dialdehyde (AD) nanofibers were prepared by green crosslinking. The degree of crosslinking could reach 50.72 %, and the diameter of electrospun fibers ranged from 446.2 to 541.8 nm. The generation of AD and the bonding of crosslinking were further confirmed by the changes on characteristic peaks and conformational ratios in the infrared spectroscopy and secondary structure analysis. High concentrations of AD led to improved thermal stabilities, mechanical properties, and hydrophobicity. And the highly crosslinked nanofibers (Z-8) owned the highest elastic modulus (24.92 MPa), tensile strength (0.28 MPa), and elongation at break (8.14 %) among five samples. Moreover, Z-8 possessed a high swelling ratio of 5.45 g/g, and a low weight loss of 6.09 %. The samples could encapsulate curcumin efficiently and show controllable release behaviors based on different AD addition. And the oxidation resistance of nanofibers gradually improved, consistent with the release performances. This study indicated AD crosslinking favored the preparation and application of zein nanofibers, and the oxidized polysaccharide acted as the green crosslinking agent, which provided reference value for the application of polysaccharides in food-related electrospun materials.


Assuntos
Curcumina , Nanofibras , Zeína , Zeína/química , Alginatos , Nanofibras/química , Resistência à Tração
12.
Gen Physiol Biophys ; 43(1): 73-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312036

RESUMO

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-ß1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-ß. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-ß1/Smad/VEGF/NCAM signaling pathway by curcumin,and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.


Assuntos
Curcumina , Glioma , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Curcumina/farmacologia , Glioma/tratamento farmacológico , Microbolhas , Moléculas de Adesão de Célula Nervosa/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Smad/metabolismo
13.
J Biochem Mol Toxicol ; 38(2): e23642, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348710

RESUMO

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.


Assuntos
Antineoplásicos , Neoplasias da Mama , Curcumina , Feminino , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Células MDA-MB-231 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Neoplasias da Mama/patologia , Autofagia , Apoptose , Linhagem Celular Tumoral
14.
J Biochem Mol Toxicol ; 38(2): e23645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348716

RESUMO

Prostate cancer (PCa) is an extremely common genitourinary malignancy among elderly men. Many evidence have shown the efficacy of curcumin (CUR) in inhibiting the progression of PCa. However, the pharmacological function of CUR in PCa is still not quite clear. In this research, CUR was found to suppress the proliferation and enhance the apoptotic rate in in vitro PCa cell models in a dose- and time-dependent manner. In a xenograft animal model, the administration of CUR contributed to a significant decrease in the growth of the xenograft tumor induced by the transplanted PC-3 cells. Ubiquitin-conjugating enzyme E2 C is implicated in the modulation of multiple types of cancers. In humans, the expression levels of UBE2C are significantly higher in PCa versus benign prostatic hyperplasia. Treatment with CUR decreased the expression of UBE2C, whereas it increased miR-483-3p expression. In contrast with the control mice, the CUR-treated mice showed a significant reduction in UBE2C and Ki-67 in PCa cells. The capability of proliferation, migration, and invasion of PCa cells was inhibited by the knockdown of UBE2C mediated by siRNA. Furthermore, dual luciferase reporter gene assay indicated the binding of miR-483-3p to UBE2C. In summary, CUR exerts its antitumor effects through regulation of the miR-483-3p/UBE2C axis by decreasing UBE2C and increasing miR-483-3p. The findings may also provide new molecular markers for PCa diagnosis and treatment.


Assuntos
Curcumina , MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Idoso , MicroRNAs/genética , MicroRNAs/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Modelos Animais de Doenças , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
15.
Medicine (Baltimore) ; 103(7): e36483, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363917

RESUMO

In this study, a series of novel compounds were synthesized by introducing the 3,4,5-trimethoxyphenyl and isatin groups into the monocarbonyl skeleton of curcumin. The possible biological activities and potential targets for these compounds were explored through network pharmacology. The results revealed that these compounds could significantly inhibit production of the inflammatory factors IL-6 and TNF-α, and suppress phosphorylation of the extracellular signal-regulated kinase (ERK) protein. Moreover, molecular docking experiments showed that the ERK protein was the potential target for these compounds. In summary, this study, through network pharmacology, presents a novel series of methoxy curcumin analogs as potent anti-inflammatory drugs.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , Humanos , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Anti-Inflamatórios/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Medicine (Baltimore) ; 103(7): e36593, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363942

RESUMO

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents. However, the nonselective effect leads to serious cardiotoxicity risk in clinical use. Curcumin is a well-known dietary polyphenol that showed a protective effect against the cardiotoxic effect of DOX. This study aimed to assess the role of curcumin in protection against DOX-induced cardiotoxicity. Potential compound and disease targets were obtained from relevant databases, and common targets were screened. Protein-protein interaction (PPI) was used to predict the core targets. Gene ontology (GO) bioprocess analysis and Kyoto encyclopedia of genes and genome enrichment analysis enriched the possible biological processes (BP), cellular components, molecular function, and signaling pathways involved. Finally, the binding of curcumin to target proteins was evaluated through molecular docking. The docking score verified the reliability of the prediction results. In total, 205 curcumin and 700 disease targets were identified. A topological analysis of the PPI network revealed 10 core targets including TP53, tumor necrosis factor-alpha (TNF), AKT1, vascular endothelial growth factor A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), signal transducer and activator of the transcription 3 (STAT3), HIF1A, MYC, epidermal growth factor receptor (EGFR), and CASP3 (Caspase-3). Furthermore, the enrichment analyses indicated that the effects of curcumin were mediated by genes related to oxidation, inflammation, toxification, cell proliferation, migration, apoptosis, wounding, metabolism, proteolysis, and the signaling pathway of calcium (Ca2+). Molecular docking showed that curcumin could bind with the target proteins with strong molecular force, exhibiting good docking activity. Curcumin has a multi-cardioprotective effect by modulating the core targets' expression in DOX-induced cardiotoxicity. This study elucidated the key target proteins and provided a theoretical basis for further exploring curcumin in the prevention and treatment of DOX-induced cardiotoxicity.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Curcumina/farmacologia , Curcumina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Farmacologia em Rede , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Reprodutibilidade dos Testes
17.
Molecules ; 29(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338373

RESUMO

This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR-) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I.


Assuntos
Neoplasias Ósseas , Quitosana , Curcumina , Nanopartículas , Osteossarcoma , Humanos , Curcumina/farmacologia , Portadores de Fármacos , Radioisótopos do Iodo , Doxorrubicina/farmacologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/radioterapia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Receptores ErbB , Linhagem Celular Tumoral
18.
Molecules ; 29(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38338458

RESUMO

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.


Assuntos
Curcumina , Ibuprofeno , Porosidade , Curcumina/química , Manitol/química , Simulação de Acoplamento Molecular , Solubilidade , Povidona/química , Água/química , Portadores de Fármacos
19.
Int J Mol Sci ; 25(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339170

RESUMO

This review aims to analyze the emerging number of studies on biological media that describe the unexpected effects of different natural bioactive antioxidants. Hormetic effects, with a biphasic response depending on the dose, or activities that are apparently non-dose-dependent, have been described for compounds such as resveratrol, curcumin, ferulic acid or linoleic acid, among others. The analysis of the reported studies confirms the incidence of these types of effects, which should be taken into account by researchers, discarding initial interpretations of imprecise methodologies or measurements. The incidence of these types of effects should enhance research into the different mechanisms of action, particularly those studied in the field of basic research, that will help us understand the causes of these unusual behaviors, depending on the dose, such as the inactivation of the signaling pathways of the immune defense system. Antioxidative and anti-inflammatory activities in biological media should be addressed in ways that go beyond a mere statistical approach. In this work, some of the research pathways that may explain the understanding of these activities are revised, paying special attention to the ability of the selected bioactive compounds (curcumin, resveratrol, ferulic acid and linoleic acid) to form metal complexes and the activity of these complexes in biological media.


Assuntos
Antioxidantes , Ácidos Cumáricos , Curcumina , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Ácido Linoleico , Inflamação/tratamento farmacológico
20.
Nanoscale ; 16(8): 4095-4104, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38333905

RESUMO

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.


Assuntos
Neoplasias da Mama , Curcumina , Neoplasias , Fotoquimioterapia , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio , Espécies Reativas de Oxigênio/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Hipóxia , Fenômenos Magnéticos , Microambiente Tumoral , Peróxido de Hidrogênio/uso terapêutico
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