Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.091
Filtrar
1.
Drug Des Devel Ther ; 18: 2869-2881, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006191

RESUMEN

Background: Parkinson's disease (PD) is the most prevalent movement disorder. Curcumin, a polyphenol with hydrophobic properties, has been proved against Parkinson. Our previous study suggested that curcumin's effectiveness in treating Parkinson's disease may be linked to the gut-brain axis, although the specific mechanism by which curcumin exerts neuroprotective effects in the brain remains unknown. Methods: The therapeutic efficacy of curcumin was evaluated using behavioral tests, immunofluorescence of tyrosine hydroxylase (TH). Network pharmacology and transcriptomics predicted the mechanisms of curcumin in PD. Activation of the phosphatidylinositol 3-kinase PI3K/AKT pathway was confirmed by quantitative polymerase chain reaction (qPCR) and immunofluorescence. Results: Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson's disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway. Conclusion: In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson's disease was revealed by our study.


Asunto(s)
Curcumina , Ratones Endogámicos C57BL , Farmacología en Red , Fármacos Neuroprotectores , Enfermedad de Parkinson , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Curcumina/farmacología , Curcumina/química , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Ratones , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Transcriptoma/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad
2.
Chem Biol Drug Des ; 104(1): e14583, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38991995

RESUMEN

In this work, a series of curcumin derivatives (1a-1h, 2a-2g, and 3a-3c) were synthesized for the suppression of castration-resistant prostate cancer cells. All synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and melting point. The in vitro cytotoxicity study shows that compounds 1a, 1e, 1f, 1h, 2g, 3a, and 3c display similar or enhanced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9, other synthesized compounds display reduced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9. Molecular docking simulation was performed to study the binding affinity and probable binding modes of the synthesized compounds with androgen receptor. The results show that all synthesized compounds exhibit higher cdocker interaction energies as compared to ASC-J9. Compounds 1h, 2g, and 3c not only show strong cytotoxicity against 22Rv1 and C4-2 cells but also exhibit high binding affinity with androgen receptor. In androgen receptor suppression study, compounds 1f and 2g show similar androgen receptor suppression effect as compared to ASC-J9 on C4-2 cells, compound 3c displays significantly enhanced AR suppression effect as compared to ASC-J9, 1f and 2g. Compounds 1a, 1e, 1f, 1h, 2g, 3a and 3c prepared in this work have significant potential for castration-resistant prostate cancer therapy.


Asunto(s)
Curcumina , Simulación del Acoplamiento Molecular , Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Curcumina/farmacología , Curcumina/química , Curcumina/síntesis química , Curcumina/metabolismo , Masculino , Humanos , Receptores Androgénicos/metabolismo , Receptores Androgénicos/química , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/química , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/metabolismo , Sitios de Unión , Unión Proteica
3.
Sci Rep ; 14(1): 16059, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992159

RESUMEN

Cholangiocarcinoma (CCA) is often diagnosed late, leading to incomplete tumor removal, drug resistance and reduced chemotherapy efficacy. Curcumin has the potential for anti-cancer activity through various therapeutic properties and can improve the efficacy of chemotherapy. We aimed to investigate the synergistic effect of a combination of curcumin and gemcitabine against CCA, targeting the LAT2/glutamine pathway. This combination synergistically suppressed proliferation in gemcitabine-resistant CCA cells (KKU-213BGemR). It also resulted in a remarkable degree of CCA cell apoptosis and cell cycle arrest, characterized by a high proportion of cells in the S and G2/M phases. Knockdown of SLC7A8 decreased the expressions of glutaminase and glutamine synthetase, resulting in inhibited cell proliferation and sensitized CCA cells to gemcitabine treatment. Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway. This approach may be an alternative strategy for the treatment of gemcitabine-resistant in CCA patients.


Asunto(s)
Apoptosis , Proliferación Celular , Colangiocarcinoma , Curcumina , Desoxicitidina , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Gemcitabina , Glutamina , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Animales , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Humanos , Curcumina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones , Glutamina/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Glutaminasa/metabolismo , Glutaminasa/antagonistas & inhibidores , Masculino
4.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000093

RESUMEN

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium graminearum, and curcumin (CUR) is a natural polyphenolic compound found in turmeric. However, the combined treatment of CUR and DON to explore the mitigating effect of CUR on DON and their combined mechanism of action is not clear. Therefore, in this study, we established four treatment groups (CON, CUR, DON and CUR + DON) to investigate their mechanism in the porcine intestinal epithelial cells (IPEC-J2). In addition, the cross-talk and alleviating potential of CUR interfering with DON-induced cytotoxic factors were evaluated by in vitro experiments; the results showed that CUR could effectively inhibit DON-exposed activated TNF-α/NF-κB pathway, attenuate DON-induced apoptosis, and alleviate DON-induced endoplasmic reticulum stress and oxidative stress through PERK/CHOP pathways, which were verified at both mRNA and protein levels. In conclusion, these promising findings may contribute to the future use of CUR as a novel feed additive to protect livestock from the harmful effects of DON.


Asunto(s)
Apoptosis , Curcumina , Estrés del Retículo Endoplásmico , Tricotecenos , Tricotecenos/farmacología , Tricotecenos/toxicidad , Animales , Curcumina/farmacología , Porcinos , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Línea Celular , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
5.
Molecules ; 29(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38998962

RESUMEN

Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring mono-alkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds 4g and 4k, showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound 4g exhibited anticancer activity with a IC50 value of 1.09 ± 0.17 µM against human colon carcinoma HCT-116 and 45.16 ± 0.92 µM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound 4g can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which 4g exerts its anti-colon cancer effect may be through inhabiting the binding of APC-Asef. Compound 4g can be used as a promising lead for further exploration of potential anticancer agents.


Asunto(s)
Antineoplásicos , Curcumina , Simulación del Acoplamiento Molecular , Triazoles , Humanos , Curcumina/farmacología , Curcumina/análogos & derivados , Curcumina/química , Curcumina/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Células A549 , Células HCT116 , Células Hep G2
6.
Int J Mol Sci ; 25(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-39000554

RESUMEN

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.


Asunto(s)
Curcumina , Células Madre Neoplásicas , Polifenoles , Neoplasias de la Mama Triple Negativas , Humanos , Curcumina/farmacología , Curcumina/análogos & derivados , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Polifenoles/farmacología , Polifenoles/química , Línea Celular Tumoral , Femenino , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química
7.
J Nanobiotechnology ; 22(1): 400, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972995

RESUMEN

Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer.


Asunto(s)
Curcumina , Células Dendríticas , Inmunoterapia , MicroARNs , Nanopartículas , Especies Reactivas de Oxígeno , Curcumina/farmacología , Curcumina/química , MicroARNs/genética , Animales , Ratones , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Inmunoterapia/métodos , Células Dendríticas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Línea Celular Tumoral , Femenino , Ratones Endogámicos C57BL , Microambiente Tumoral/efectos de los fármacos , Ratones Endogámicos BALB C , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología
8.
Chin J Dent Res ; 27(2): 169-174, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38953482

RESUMEN

OBJECTIVE: To evaluate the effect of entrapment of curcumin within liposomal formulation and the sustained release attitude of the formulated liposomal gel on periodontal defects in diabetic patients in clinical and biochemical terms. METHODS: Thirty diabetic patients with periodontitis were randomly assigned to three equal groups and ten healthy participants were assigned as the control group. Group I was subjected to scaling and root planing (SRP) with application of sustained release liposomal curcumin gel. Group II was subjected to scaling and root planning with application of curcumin gel. Group III was subjected to scaling and root planning with application of placebo gel. Group IV (control group), no intervention was done. The following parameters were evaluated before treatment and after 6 and 12 weeks: plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and total antioxidant capacity (TAC). RESULTS: All study groups showed improvement in clinical and biochemical parameters that are statistically significant. Upon comparing the results of treatment modalities, the highest improvement was achieved in group I followed by group II then group III. CONCLUSION: Sustained release liposomal curcumin gel enhanced the antioxidant capacity, decreased the inflammatory mediators and showed more improvement in clinical outcome for treatment of periodontitis in diabetic patients.


Asunto(s)
Curcumina , Preparaciones de Acción Retardada , Liposomas , Humanos , Curcumina/uso terapéutico , Curcumina/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Raspado Dental , Periodontitis/tratamiento farmacológico , Aplanamiento de la Raíz , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación , Índice Periodontal
9.
J Biochem Mol Toxicol ; 38(7): e23760, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38953502

RESUMEN

Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aß1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kß), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aß1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.


Asunto(s)
Alcaloides , Benzodioxoles , Lesiones Encefálicas , Curcumina , Ciclofosfamida , Piperidinas , Alcamidas Poliinsaturadas , Animales , Alcamidas Poliinsaturadas/farmacología , Benzodioxoles/farmacología , Curcumina/farmacología , Piperidinas/farmacología , Alcaloides/farmacología , Ratas , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Masculino , Lesiones Encefálicas/inducido químicamente , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Lesiones Encefálicas/prevención & control , Ratas Wistar , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Estrés Oxidativo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología
10.
Int J Nanomedicine ; 19: 6643-6658, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38979532

RESUMEN

Purpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D). Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting. Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK. Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Glucosa , Metabolismo de los Lípidos , Hígado , Células Madre Mesenquimatosas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Hep G2 , Glucosa/metabolismo , Ratones , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Curcumina/farmacología , Curcumina/química , Curcumina/administración & dosificación , Resistencia a la Insulina , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Diabetes Mellitus Experimental/metabolismo
11.
Breast Cancer Res ; 26(1): 114, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978121

RESUMEN

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.


Asunto(s)
Catequina , Curcumina , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-bcl-2 , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química , Catequina/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Humanos , Curcumina/farmacología , Curcumina/química , Curcumina/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Unión Proteica , Farmacóforo
12.
J Microencapsul ; 41(5): 390-401, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38945157

RESUMEN

Green-synthesis of biodegradable polymeric curcumin-nanoparticles using affordable biodegradable polymers to enhance curcumin's solubility and anti-oxidative potential. The curcumin-nanoparticle was prepared based on the ionic-interaction method without using any chemical surfactants, and the particle-size, zeta-potential, surface-morphology, entrapmentefficiency, and in-vitro drug release study were used to optimise the formulation. The antioxidant activity was investigated using H2DCFDA staining in the zebrafish (Danio rerio) model. The mean-diameter of blank nanoparticles was 178.2 nm (±4.69), and that of curcuminnanoparticles was about 227.7 nm (±10.4), with a PDI value of 0.312 (±0.023) and 0.360 (±0.02). The encapsulation-efficacy was found to be 34% (±1.8), with significantly reduced oxidative-stress and toxicity (∼5 times) in the zebrafish model compared to standard curcumin. The results suggested that the current way of encapsulating curcumin using affordable, biodegradable, natural polymers could be a better approach to enhancing curcumin's water solubility and bioactivity, which could further be translated into potential therapeutics.


Asunto(s)
Antioxidantes , Quitosano , Curcumina , Tecnología Química Verde , Goma Arábiga , Nanopartículas , Pez Cebra , Animales , Curcumina/farmacología , Curcumina/química , Curcumina/administración & dosificación , Curcumina/farmacocinética , Nanopartículas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/administración & dosificación , Quitosano/química , Goma Arábiga/química , Portadores de Fármacos/química , Liberación de Fármacos , Solubilidad , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula
13.
Clin Nutr ESPEN ; 62: 57-65, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901949

RESUMEN

BACKGROUND: Coronary artery bypass graft (CABG) is one of the preferred treatments for patients with heart problems, especially in individuals with other comorbidities and when multiple arteries are narrowed. This study aimed to assess the effects of administrating curcumin-piperine on patients who underwent CABG surgery. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial, in which 80 eligible adults who underwent CABG surgery, were randomized into 4 groups. Patients received 3 tablets daily for 5 days after the surgery, which contained curcumin-piperine (each tablet contained 500 mg curcumin +5 mg piperine) or a placebo (each tablet contained 505 mg maltodextrin). Group A received 3 placebo tablets, group B received 2 placebos and one curcumin-piperine tablet, group C received 1 placebo and 2 curcumin-piperine tablets, and group D received 3 curcumin-piperine tablets. Before and after the intervention, C-reactive protein (CRP), total antioxidant capacity (TAC), cardiometabolic factors, clinical outcomes, and 28-day mortality were evaluated. RESULTS: Between-group analysis showed that CRP significantly decreased (P = 0.028), and TAC significantly increased (P = 0.033) after the intervention (Post hoc analysis showed that for CRP, the difference was between group B and D, and for TAC was between group C and D). Between-group analysis also showed that creatine kinase mono-phosphate (CK-MB) marginally reduced (P = 0.077); however, changes for troponin I (P = 0.692), lactate dehydrogenase (LDH) (P = 0.668), ejection fraction (P = 0.340), and arterial fibrillation (P = 0.99) were not significant. Blood urea nitrogen (P = 0.820) and serum creatinine (P = 0.244) did not show notable changes between groups. CONCLUSION: Supplementation with curcumin-piperine had a promising effect on serum CRP and TAC. It also had a favorable impact on CK-MB among patients who underwent CABG surgery. TRIAL REGISTRATION: IRCT20201129049534N4, available on https://en.irct.ir/trial/56930.


Asunto(s)
Alcaloides , Fibrilación Atrial , Benzodioxoles , Biomarcadores , Proteína C-Reactiva , Puente de Arteria Coronaria , Curcumina , Suplementos Dietéticos , Piperidinas , Alcamidas Poliinsaturadas , Humanos , Curcumina/administración & dosificación , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Masculino , Benzodioxoles/uso terapéutico , Femenino , Persona de Mediana Edad , Método Doble Ciego , Biomarcadores/sangre , Fibrilación Atrial/tratamiento farmacológico , Anciano , Proteína C-Reactiva/metabolismo , Resultado del Tratamiento , Inflamación , Antioxidantes
14.
Carbohydr Polym ; 341: 122330, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38876726

RESUMEN

Polyelectrolyte complexes (PECs) were elaborated from chitosan as cationic polymer and carboxy-methylpullulan (CMP), hyaluronic acid (HA) and their derivatives grafted with aminoguaiacol (G) with different degrees of substitution (DSGA) with the aim of obtaining nanogels for drug delivery. For each couple of polysaccharides, the charge ratios giving the smaller size with the lower PDI were selected to produce PECs. CMP_CHIT and CMP-G_CHIT PECs had smaller sizes (220-280 nm) than HA_CHIT and HA-G_CHIT PECs (280-390 nm). PECs were stable at 4 °C during 28 days at pH 5. In phosphate buffer saline (PBS) at pH 7.4, at 4 °C, a better stability of PECs based on CMP-G derivatives was observed. The hydrophobic associations between aminoguaiacol groups (highlighted by measurements of pyrene fluorescence) led to a better PECs' stabilization in PBS. The PECs' antioxidant and antibacterial activities were demonstrated and related to the DSGA. Diclofenac and curcumin were used as drug models: their loading reached 260 and 53 µg/mg PEC, respectively. The release of diclofenac in PBS at 37 °C followed a quasi-Fickian diffusion mechanism with release constant between 0.88 and 1.04 h-1. The curcumin release followed a slow linear increase in PBS/EtOH (60/40 V/V) with an effect of DSGA.


Asunto(s)
Antibacterianos , Quitosano , Curcumina , Ácido Hialurónico , Ácido Hialurónico/química , Quitosano/química , Quitosano/análogos & derivados , Curcumina/química , Curcumina/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Guayacol/química , Guayacol/análogos & derivados , Guayacol/farmacología , Diclofenaco/química , Diclofenaco/farmacología , Portadores de Fármacos/química , Polielectrolitos/química , Sistemas de Liberación de Medicamentos/métodos , Nanogeles/química , Glucanos/química , Escherichia coli/efectos de los fármacos , Liberación de Fármacos
15.
ACS Appl Mater Interfaces ; 16(24): 30997-31010, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38838270

RESUMEN

The importance of amyloid nanofibrils made from food proteins is rising in diverse fields, such as biomedicine and food science. These protein nanofibrils (PNFs) serve as versatile and sustainable building blocks for biomaterials, characterized by their high ß-sheet content and an ordered hydrogen bond network. These properties offer both stability and flexibility, along with an extreme aspect ratio and reactive functional groups. Plant-derived amyloid nanofibrils, such as soy protein isolate (SPI) PNFs, are increasingly favored due to their affordability and sustainability compared with animal proteins. This study aimed to explore the formation and application of SPI amyloid-like aggregates (SPIA) and their nanoencapsulation of curcumin (Cur) for biomedical purposes, particularly in wound healing. Under specific conditions of low pH and high temperature, SPIA formed, exhibited an amyloid nature, and successfully encapsulated Cur, thereby enhancing its stability and availability. Spectroscopic and microscopic analyses confirmed structural changes in SPIA upon the incorporation of Cur and the fabrication of SPIA@Cur. The obtained results indicate that in the presence of Cur, SPIA forms faster, attributed to accelerated SPI denaturation, an increased nucleation rate, and enhanced self-assembly facilitated by Cur's hydrophobic interactions and π-π stacking with SPI peptides. In vitro studies demonstrated the biocompatibility, biodegradability, and antioxidant properties of SPIA@Cur along with controlled release behavior. In vivo experiments in male Wistar rats revealed that both SPIA and SPIA@Cur significantly accelerate wound closure compared with untreated wounds, with SPIA@Cur showing slightly better efficacy. The histological analysis supported enhanced wound healing, indicating the potential of SPIA@Cur for biomedical applications.


Asunto(s)
Amiloide , Curcumina , Proteínas de Soja , Cicatrización de Heridas , Curcumina/química , Curcumina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Proteínas de Soja/química , Proteínas de Soja/farmacología , Animales , Amiloide/química , Amiloide/metabolismo , Ratas , Humanos , Antioxidantes/química , Antioxidantes/farmacología , Nanofibras/química
16.
Clin Nutr ESPEN ; 62: 253-259, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38857152

RESUMEN

BACKGROUND AND AIM: Curcumin is a polyphenolic natural compound that has been used to treat various ailments such as symptoms of anxiety. However, the findings of studies regarding the anti-anxiety properties of curcumin are controversial. This review aims to evaluate if there are clinical benefits of curcumin in patients with symptoms of anxiety. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) from the database inception to August 16, 2023. The random-effects model was used to estimate the standard mean difference (SMD). RESULTS: A total of eight RCTs involving 567 participants were included in the analysis. A pooled analysis showed a significant effect of curcumin on anxiety symptoms (SMD: -1.56; 95% CI: -2.48, -0.64, p < 0.001; I2 = 95.6%, p-heterogeneity< 0.001). CONCLUSION: Present meta-analysis demonstrated that curcumin intake might contribute to alleviation of anxiety disorder. Due to the limited number of studies included, it is necessary to conduct more high-quality studies to confirm the clinical efficacy of curcumin.


Asunto(s)
Ansiedad , Curcumina , Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Curcumina/uso terapéutico , Humanos , Ansiedad/tratamiento farmacológico , Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico
17.
Reprod Fertil Dev ; 362024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38870343

RESUMEN

Context Carbon tetrachloride (CCl4 ) is a chemical that is still widely used in industry and has been shown to cause structural defects in rat testicles through oxidative stress. Aims In our study, the effect of curcumin on CCl4 -mediated testicular damage was investigated. Methods Twenty-four adult Wistar albino male rats weighing 300-350g were divided into four groups: control group (olive oil was applied by gavage every consecutive day for 3weeks); curcumin and CCl4 +curcumin groups (200mg/kg curcumin dissolved in olive oil was given by gavage once a day, every consecutive day for 3weeks); and CCl4 and CCl4 +curcumin groups (0.5mL/kg CCl4 was dissolved in olive oil at a ratio of 1/1 and given by i.p. injection every other day for 3weeks). Tissue samples were examined histopathologically, histomorphometrically, immunohistochemically and biochemically. Key results CCl4 disrupted both testicular morphology and testosterone synthesis, whereas curcumin treatment resulted in an improvement in testicular morphology and biochemical parameters, as well as a decrease in caspase-3 and tumour necrosis factor-α expression. Conclusions Curcumin has a protective effect on testicular tissue damage caused by CCl4 with its anti-inflammatory, antiapoptotic and antioxantioxidant properties. Implications Curcumin can prevent testicular damage due to CCl4 , an environmental pollutant.


Asunto(s)
Tetracloruro de Carbono , Curcumina , Estrés Oxidativo , Ratas Wistar , Testículo , Testosterona , Animales , Masculino , Curcumina/farmacología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/metabolismo , Testosterona/sangre , Ratas , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Enfermedades Testiculares/prevención & control , Enfermedades Testiculares/patología , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/metabolismo
18.
Nutrients ; 16(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38892660

RESUMEN

This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.


Asunto(s)
Curcumina , Inflamación , Enfermedades Metabólicas , Ensayos Clínicos Controlados Aleatorios como Asunto , Curcumina/farmacología , Curcumina/administración & dosificación , Humanos , Inflamación/tratamiento farmacológico , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedad Crónica , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Resistencia a la Insulina , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Metaanálisis como Asunto , Antioxidantes/farmacología
19.
Molecules ; 29(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38893567

RESUMEN

Curcumin (Cur) is a phytochemical with various beneficial properties, including antioxidant, anti-inflammatory, and anticancer activities. However, its hydrophobicity, poor bioavailability, and stability limit its application in many biological approaches. In this study, a novel amphiphilic chitosan wall material was synthesized. The process was carried out via grafting chitosan with succinic anhydride (SA) as a hydrophilic group and deoxycholic acid (DA) as a hydrophobic group; 1H-NMR, FTIR, and XRD were employed to characterize the amphiphilic chitosan (CS-SA-DA). Using a low-cost, inorganic solvent-based procedure, CS-SA-DA was self-assembled to load Cur nanomicelles. This amphiphilic polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 0.093 mg·mL-1. Cur-loaded nanomicelles were prepared by self-assembly and characterized by the Nano Particle Size Potential Analyzer and transmission electron microscopy (TEM). The mean particle size of the spherical Cur-loaded micelles was 770 nm. The drug entrapment efficiency and loading capacities were up to 80.80 ± 0.99% and 19.02 ± 0.46%, respectively. The in vitro release profiles of curcumin from micelles showed a constant release of the active drug molecule. Cytotoxicity studies and toxicity tests for zebrafish exhibited the comparable efficacy and safety of this delivery system. Moreover, the results showed that the entrapment of curcumin in micelles improves its stability, antioxidant, and anti-inflammatory activity.


Asunto(s)
Antioxidantes , Quitosano , Curcumina , Micelas , Curcumina/farmacología , Curcumina/química , Quitosano/química , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Animales , Pez Cebra , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Tensoactivos/química
20.
Int J Nanomedicine ; 19: 5721-5737, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895153

RESUMEN

Purpose: Curcumin nanocrystals (Cur-NCs) were prepared by hot melt extrusion (HME) technology to improve the dissolution and bioavailability of curcumin (Cur). Methods: Cur-NCs with different drug-carrier ratios were prepared by one-step extrusion process with Eudragit® EPO (EEP) as the carrier. The dispersed size and solid state of Cur in extruded samples were characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The thermal stability of Cur was analyzed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC). Dissolution and pharmacokinetics were studied to evaluate the improvement of dissolution and absorption of Cur by nano-preparation. Results: Cur-NCs with particle sizes in the range of 50~150 nm were successfully prepared by using drug-carrier ratios of 1:1, 2:1 and 4:1, and the crystal form of Cur was Form 1 both before and after HME. The extrudate powders showed very efficient dissolution with the cumulative dissolution percentage of 80% in less than 2 min, and the intrinsic dissolution rates of them were 13.68 ± 1.20 mg/min/cm2, 11.78 ± 0.57 mg/min/cm2 and 4.35 ± 0.20 mg/min/cm2, respectively, whereas that of pure Cur was only 0.04 ± 0.00 mg/min/cm2. The TGA data demonstrated that the degradation temperature of Cur was about 250 °C, while the HPLC results showed Cur was degraded when extruded at the temperature over 150 °C. Pharmacokinetic experiment showed a significant improvement in the absorption of Cur. The Cmax of Cur in the Cur-NC group was 1.68 times that of pure Cur group, and the Cmax and area under the curve (AUC0-∞) of metabolites were 2.79 and 4.07 times compared with pure Cur group. Conclusion: Cur-NCs can be prepared by HME technology in one step, which significantly improves the dissolution and bioavailability of Cur. Such a novel method for preparing insoluble drug nanocrystals has broad application prospects.


Asunto(s)
Disponibilidad Biológica , Curcumina , Tecnología de Extrusión de Fusión en Caliente , Nanopartículas , Tamaño de la Partícula , Solubilidad , Curcumina/farmacocinética , Curcumina/química , Curcumina/administración & dosificación , Nanopartículas/química , Animales , Tecnología de Extrusión de Fusión en Caliente/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Masculino , Rastreo Diferencial de Calorimetría , Estabilidad de Medicamentos , Liberación de Fármacos , Difracción de Rayos X , Ácidos Polimetacrílicos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...