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1.
Heliyon ; 10(11): e31678, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38832286

RESUMEN

The effective treatment of cancer presents numerous challenges, including drug resistance and the risk of detrimental effects on normal tissues. Harmine, a beta-carboline alkaloid, has demonstrated diverse biological properties. This study aimed to synthesize and characterize harmine encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (Ha-PLGA-NPs) to investigate their potential as agents against cancer and angiogenesis. The synthesized Ha-PLGA-NPs were thoroughly characterized, exhibiting a connected rod-shaped crystal which some retaining the spherical shape of nanoparticles with an average size of 302.96 nm. Furthermore, the nanoparticles demonstrated a dispersion index of 0.23 and a surface charge of -16.51 mV. In vitro cytotoxicity assays conducted on the breast cancer cell line (MCF-7) revealed that Ha-PLGA-NPs possessed significant cytotoxic properties, with an observed IC50 value of 87.74 µg/mL. Notably, no substantial cytotoxicity was observed in human foreskin fibroblasts, indicating a favorable selectivity towards cancer cells. Evaluation of the anti-angiogenic activity of Ha-PLGA-NPs demonstrated a concentration-dependent inhibition of angiogenesis. Mechanistic investigations indicated that the observed inhibition was mediated through the regulation of key genes involved in angiogenesis, including caspase 3, caspase 9, VEGF, and VEGF-R. In vivo studies involving dietary administration of Ha-PLGA-NPs in mice revealed improvements in weight gain, feed intake, liver enzyme levels, and redox potential. These findings underscore the potential of Ha-PLGA-NPs as a promising therapeutic agent for cancer treatment. The observed effects are attributed to their ability to induce programmed cell death and inhibit angiogenesis, thus offering a multifaceted approach to combat cancer.

2.
Discov Oncol ; 15(1): 100, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38568336

RESUMEN

Diosgenin as a potential phytoconstituent and steroidal saponin manifested significant anticancer agents against various cancers. To enhance its solubility and bioavailability in cancer treatment, we loaded diosgenin (PubChem CID: 99474) in poly(lactic-co-glycolide) (PLGA) nanoparticle coated with folic acid-chitosan (Da-PFC-NPs). The diosgenin nano-formulation was characterized and its antioxidant and anticancer properties were surveyed respectively. The obtained results illustrated that the Da-PFC-NPs were spherical and stable with a size of 218 nm and a polydispersity index of 0.41. The Da-PFC-NPs indicated potential free radical scavenging using ABTS and DPPH assay. Meanwhile, it demonstrated selective toxicity against the TUBO breast cancer cell with IC50 values of 104.45 µg/ml and did not show toxicity on normal cells (I929 cell line). The invivo funding exhibited that Da-PFC-NPs notably  altered the liver enzymes (AST, ALT, ALP) and immunoglobulins (IgA, IgG, IgM). Besides that, different doses of Da-PFC-NPs (50 and 100 mg/kg) remarkedly enhance the expression of caspase 3 and decrease HER2 genes. In light of this experiment, we can conclude that Da-PFC-NPs have promise as novel carrier for improving the delivery of diosgenin in cancer therapy.

3.
Biotechnol Appl Biochem ; 71(3): 641-650, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38326022

RESUMEN

Colon cancer is one of the leading causes of death among various types of cancer. Despite the significant progress made in cancer treatment, chemotherapy resistance and various side effects are still prevalent. The objective of this study is to assess the therapeutic potential of phenolic-rich fraction encapsulated nanoliposome (PRF-NLs) of Salvia leriifolia Benth in the treatment of colon cancer in mice. Initially, the phenolic-rich fraction (PRF) was extracted and then encapsulated into nanoliposomes. The physicochemical properties of the nanoliposomes were evaluated using dynamic light scattering, zeta potential, and field emission scanning electron microscopy. Subsequently, 24 mice with HT-29 colon cancer cells were divided into three groups, and the anticancer effects of PRF-NLs were measured. The results showed that the ethyl acetate fraction of S. leriifolia was the highest PRF containing 14.27 ± 2.39 mg (gallic acid) GA/g DW (dry weight), and the PRF successfully loaded into the nanoliposome structure resulted in the synthesis of nanoliposomes with a nanometer size and spherical shape and homogenous dispersion. Some of the abundant bioactive phenolic compounds in the nanoliposome-loaded PRF are salicylic acid and naringin. The average daily weight gain and food intake, and changes in the expression of caspase 3, Bax (Bcl-2 associated X-protein), and Bcl2 (B-cell lymphoma 2), inducible nitric oxide synthase genes, were observed in the mice group induced colorectal cancer cells. At a dose of 100 mg TPC (total phenolic content)/kg BW/day, the nonencapsulated PRF dietary addition improved these parameters; however, the potential shown by nanoliposome-encapsulated PRF than the nonencapsulated PRF in enhancing health parameters in mice was higher. The developed intestinal absorption and bioavailability of nanoliposome-encapsulated PRF contribute to its increased health-promoting activity. Thereby, the synthesized nanoliposome may be a potential natural anticancer drug to prevent colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Liposomas , Nanopartículas , Fenoles , Salvia , Animales , Ratones , Liposomas/química , Humanos , Fenoles/farmacología , Fenoles/química , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Salvia/química , Nanopartículas/química , Células HT29 , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Masculino , Proliferación Celular/efectos de los fármacos
4.
Iran J Basic Med Sci ; 27(2): 118-194, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38234673

RESUMEN

Objectives: Bone tissue engineering is considered a new method in the treatment of bone defects and can be an effective alternative to surgery and bone grafting. The use of adipose tissue mesenchymal stem cells (ADMSCs) on synthetic polymer scaffolds is one of the new approaches in bone tissue engineering. In this study, we aimed to investigate the effect of laminin coating on biocompatibility and osteogenic differentiation of ADMSCs seeded on polycaprolactone (PCL) scaffolds. Materials and Methods: The morphology of the electrospun scaffold was evaluated using a scanning electron microscope (SEM). Cell proliferation and cytotoxicity were determined by MTT assay. The adipogenic and osteogenic differentiation potential of the cells was evaluated. The osteogenic differentiation of ADMSCs cultured on the PCL scaffold coated with laminin was assessed by evaluating the level of alkaline phosphatase (ALP) activity, intracellular calcium content, and expression of bone-specific genes. Results: The results showed that the ADMSCs cultured on PCL/laminin showed enhanced osteogenic differentiation compared to those cultured on non-coated PCL or control medium (P<0.05). Conclusion: It seems that laminin enhances the physicochemical properties and biocompatibility of PCL nanofiber scaffolds; and by modifying the surface of the scaffold, improves the differentiation of ADMSCs into osteogenic cells.

5.
Biol Trace Elem Res ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38285321

RESUMEN

Lead (Pb) poisoning is a widespread issue in both developed and developing countries that poses a significant public health challenge. Our study aimed to explore the impact of Levilactobacillus brevis strains on inflammatory and antioxidant gene expression in the liver and brain of mice exposed to oxidative stress caused by Pb. We began by evaluating Pb absorption by Levilactobacillus brevis strains (ARKA-CH-1 (A1) and ARKA-CH-6 (A6)) using the inductively coupled plasma mass spectrometry (ICP-MS) in vitro to identify the most effective strain. We then divided four groups of BALB/c mice into control and experimental groups and treated them for 30 days. The control group received a normal diet, while the experimental groups consumed lead-containing water (0.6 g/L) with or without Levilactobacillus brevis strains. Following the experiments, we collected blood samples to test liver markers, antioxidant enzymes, and immunoglobulins. We also used real-time PCR to examine the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) genes. The results showed that the A1 strain was the most effective in absorbing Pb. The Pb exposure led to an increase in liver enzyme values and a decrease in antioxidant enzyme activity and immunoglobulin factors. However, the combination of A1 and A6 strains had a greater effect in reducing inflammatory enzymes and increasing antioxidant enzymes. Furthermore, we observed a significant increase in iNOS gene expression and a notable decrease in SOD gene expression with Pb consumption. However, the combination of A1 and A6 strains had a synergistic effect in reducing iNOS and increasing SOD gene expression. In conclusion, Levilactobacillus brevis A1 strain alone or in combination with the A6 strain could be a promising strategy to mitigate the oxidative stress symptoms in mice challenged by lead-induced toxicity.

6.
Chem Biodivers ; 21(1): e202300187, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38164058

RESUMEN

In this study, we developed Solid Lipid Nanoparticles (SLN-NPs) loaded with Artemisia vulgaris essential oil and coated with folic acid-chitosan (AVEO-SCF-NPs) to enhance drug delivery in biotechnology and pharmaceutical sectors. AVEO-SCF-NPs were synthesized using homogenization and ultra-sonication methods and comprehensively characterized. These nanoparticles exhibited a particle size of 253.67 nm, Polydispersity Index (PDI) of 0.26, zeta potential (ζ-p) of +39.96 mV, encapsulation efficiency (%EE) of 99.0 %, and folic acid binding efficiency (% FB) of 46.25 %. They effectively inhibited MCF-7, HT-29, and PC-3 cancer cells with IC50 values of 48.87 µg/mL, 88.48 µg/mL, and 121.34 µg/mL, respectively, and demonstrated antibacterial properties against Gram-positive strains. AVEO-SCF-NPs also exhibited scavenging effects on ABTS (IC50 : 203.83 µg/mL) and DPPH (IC50: 680.86 µg/mL) free radicals and inhibited angiogenesis, as confirmed through CAM and qPCR assays. Furthermore, these nanoparticles induced apoptosis, evidenced by up-regulation of caspase 3 and 9, down-regulation of TNF-α genes, and an increase in SubG1 phase cells. The high loading capacity of SCF-NPs for AVEO, coupled with their multifaceted biological properties, highlights AVEO-SCF-NPs as promising candidates for cancer therapy in the biotechnology and pharmaceutical industries.


Asunto(s)
Artemisia , Quitosano , Liposomas , Nanopartículas , Humanos , Quitosano/farmacología , Quitosano/química , Ácido Fólico/química , Nanopartículas/química
7.
Am J Stem Cells ; 12(4): 83-91, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38021455

RESUMEN

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) hold promise for bone tissue engineering because of their ability to differentiate into a variety of cell lineages. In tissue engineering, composite scaffolds made of natural and synthetic polymers have also attracted interest. Modification of scaffolds with various substances, including Aloe Vera, is expected to play a useful role in the repair of damaged tissues, including bone. METHOD: ADSCs were isolated and seeded in three groups on an Aloe Vera-modified PCL scaffold: 1. Polycaprolactone (PCL) scaffold group, 2. PCL/Aloe Vera scaffold group, and 3. TCPS (Tissue Culture Polystyrene) group. Subsequently, staining with Oil red and Alizarin Red was performed to assess the ability of ADSCs to differentiate into fat and bone cells. Cell viability was determined by the resazurin assay on days 1, 3, and 5. Calcium content and alkaline phosphatase activity (ALP) were determined with kits on days 7, 14, and 21. RNA was extracted, and cDNA was synthesized. Finally, the expression of marker genes for bone differentiation like osteogenic markers such as Osteonectin (ON), Osteocalcin (OC), RUNX Family Transcription Factor 2 (RUNX2), Collagen type I alpha 1 (COL1) was evaluated by real-time PCR. RESULTS: Aloe vera-treated PCL scaffolds showed improved biocompatibility compared with untreated scaffolds (P<0.05). In addition, treated scaffolds promoted osteogenic differentiation of ADSCs, as evidenced by increased expression of osteogenic markers such ON, OC, RUNX2, COL1 compared with PCL scaffold and TCPS (P<0.05). Furthermore, ALP and calcium content assay confirmed improved mineral deposition on PCL scaffolds treated with Aloe vera, indicating enhanced osteoconductivity (P<0.05). CONCLUSION: Our data suggest that a PCL scaffold mixed with Aloe Vera gel has promising osteoconductive potential, which can be used as a natural polymer for tissue engineering of bone and promote bone regeneration.

8.
Biotechnol Appl Biochem ; 70(6): 2088-2096, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37694540

RESUMEN

There are various types of bioactivities that have been reported for Heracleum persicum species, such as antioxidant, anti-inflammatory, and cytotoxicity properties. In the current study, the bio-accessibility of H. persicum bioactive compounds was improved by purifying its phenolic-enriched fractions (PEF) and encapsulating them into nanoliposomes to analyze its cytotoxic impacts on mice testicular tissue and their fertility status. Nano liposomal H. persicum PEF (NL-HPEF) was prepared by ultrasound-based encapsulation of HPEF and L-agranular lecithin mixture. The size, morphology, and stability of NL-HPEF were characterized by dynamic light scattering, field emission scanning electron microscopy, and zeta potential analysis. The 18 white male Balb/c mice (20-25 g) at 3 treatment groups were provided to study the NL-HPPF cytotoxicity by measuring the mice liver enzyme including aspartate aminotransferase (AST), ALP and alanine aminotransferase (ALT), testis lipid peroxidation, and testicular tissue destruction levels. Moreover, the mice's fertility was evaluated by studying the Adam3, Prm1, Spata19, and Tnp2 gene expression in the testicular tissues. The obtained results manifested that the synthesized NL-HPEF was stable (193.7 nm) and exhibited a notable cytotoxic impact on the mice's liver (ALT and AST enhancement levels) and testicular tissues. Moreover, their increasing treatment doses impaired the male mice's fertility by decreasing the sperm count, viability, and motility. In addition, fertility suppression was verified by decreasing serum testosterone and downregulating the Adam3, Prm1, Spata19, and Tnp2 gene expression in their testicular tissues. The male mice's fertility was significantly (p < 0.05) suppressed by increasing treatment doses of NL-HPEF. Hence, the NL-HPEF could be considered a promising alternative to replace the male chemical contraceptives drugs.


Asunto(s)
Heracleum , Masculino , Ratones , Animales , Heracleum/química , Ratones Endogámicos BALB C , Extractos Vegetales/farmacología , Extractos Vegetales/química , Semillas , Espermatogénesis
9.
Genes (Basel) ; 14(8)2023 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-37628599

RESUMEN

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.


Asunto(s)
Allium , Regulación de la Expresión Génica , Allium/química , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Fitosomas , Extractos Vegetales/farmacología , Fenoles/farmacología , Nanoestructuras , Femenino , Animales , Ratones , Ratones Endogámicos BALB C , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/enzimología , Peso Corporal , Antineoplásicos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos
10.
Mol Biol Rep ; 50(8): 6469-6479, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37326747

RESUMEN

BACKGROUND: The notion of cancer therapy is intrinsically subjected to multiple challenges due to the drug resistance and drug toxicity for normal tissues. Herniarin (7-methoxycoumarin) belongs to the naturally occurring aromatic phytochemicals and coumarins. Considering the boosting effect of nanocarriers in drug delivery, we investigated the proapoptotic, anti-metastatic properties, and molecular mechanism of herniarin-loaded solid lipid nanoparticles on human gastric adenocarcinoma (AGS), human colon adenocarcinoma (HT-29), human pancreatic carcinoma (Panc-1), and normal human skin fibroblast (HFF) cell lines. METHODS AND RESULTS: The cytotoxicity of synthesized nanoparticle have been tested using MTT assay. The obtained results manifested that concentration of herniarin that exerts 50% cell growth inhibition (IC50) against HT-29, AGS, and Panc-1 was calculated 138.34, 123.46, and 83.744 µL, respectively. Given that nanoparticles showed lowest IC50 values on Panc-1 cell line, these cells were selected for further analysis. The apoptosis induction and cell cycle arrest were examined performing real-time PCR, flow cytometry, and DAPI/acridine orange-propidium iodide staining. The expression of apoptosis-related genes, including BCL-2, was decreased, while the expression of CASP9, CASP8, and CASP3 was increased in response to the treatment. Moreover, the expression of metastasis-related gene (MMP2) was significantly suppressed under Her-SLN-NPs treatment. According to the flow cytometry findings, we observed no cell cycle arrest at any stage. CONCLUSION: Our funding manifested herniarin encapsulated solid lipid nanoparticles has potent therapeutic target against Panc-1 cell line.


Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Nanopartículas , Neoplasias Pancreáticas , Humanos , Nanopartículas/química , Neoplasias Pancreáticas/metabolismo , Apoptosis , Células HT29 , Línea Celular Tumoral , Neoplasias Pancreáticas
11.
IET Nanobiotechnol ; 17(5): 425-437, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37191102

RESUMEN

The present research aims to encapsulate lawsone in polylactic-co-glycolic acid (PLGA) nanoparticles modified with folic acid (FA) and chitosan (CS) to study its anticancer effects against Panc-1 cells. The nanoparticles were analysed in means of shape/size and zeta potential index using scanning electron microscope and dynamic light scattering. High-performance liquid chromatography was applied to evaluate the lawsone entrapment efficacy. The authors performed acridine orange/propidium iodide staining and flow cytometry to monitor apoptosis induction and cell cycle arrest. The expressions of apoptosis-related genes (BAX and BCL-2) were assessed by real time PCR. Nanoparticle antioxidative and antibacterial activities were examined by DPPH/ABTS scavenging assay, disk diffusion method, and minimum inhibitory concentration and minimum bactericidal concentration evaluation. The NPs were 229.65 nm, the encapsulation efficiency was 81%. The concentration of lawsone that exerts 50% cell growth inhibition (IC50 ) against Panc-1 cells was calculated 118.4 µL. Apoptosis induction was evidenced by the increased number of orange cells and increased proportion of cells in G1-Sub phase respectively. Moreover, lawsone-loaded nanoparticle upregulated BAX gene expression, while downregulated BCL2expression, suggesting the activation of apoptotic pathway. The observed cytotoxic/apoptotic properties suggest that Lawson-loaded PLGA-FA-CS-NPs hold a great potential in pancreatic cancer treatment.


Asunto(s)
Quitosano , Nanopartículas , Neoplasias , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Quitosano/química , Ácido Poliglicólico/química , Ácido Fólico/química , Ácido Láctico/química , Ácido Láctico/farmacología , Glicoles/farmacología , Proteína X Asociada a bcl-2/farmacología , Apoptosis , Nanopartículas/química , Portadores de Fármacos/química
12.
Environ Sci Pollut Res Int ; 30(20): 58654-58662, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36991200

RESUMEN

Mycotoxins are the secondary fungal metabolites generally produced by wide range of fungi including aflatoxins (AF), ochratoxin A (OTA), fumonisins (FB), zearalenone (ZEN), and deoxynivalenol (DON). Nowadays, they are main concern to food and agricultural commodities due to undesirable health and socio-economic effect. This investigation was designed to synthesized microcapsules loaded the bioactive compounds of date seed and evaluated its inhibitory activities in mice received mold-contaminated diet. The finding revealed that the developed microcapsule is homogenous and mostly spherical with size of 2.58 µm with acceptable PDI of 0.21. The main phytochemical has been confirmed by HPLC analysis were xylose, fructose, mannose, glucose, and galactose with the respective values of 41.95%, 2.24%, 5.27%, and 0.169%. The in vivo analyses manifested that the mice received date seed microcapsules significantly (p < 0.05) improved the average daily weight gain, feed intake, liver enzymes (ALT, ALP, and AST), and lipid peroxidation values compare to mice group received mycotoxin-contaminated diet. Furthermore, encapsulation date seed bioactive compounds notably up-regulated the expression of GPx, SOD, IFN-γ, and IL-2 genes while down-regulated the iNOS gene. Consequently, the novel microcapsules loaded date seed is suggested to be considered as a promising mycotoxin inhibitor.


Asunto(s)
Micotoxinas , Tricotecenos , Animales , Ratones , Micotoxinas/toxicidad , Micotoxinas/análisis , Cápsulas , Tricotecenos/análisis , Tricotecenos/toxicidad , Contaminación de Alimentos/análisis , Dieta , Hongos , Alimentación Animal/análisis , Extractos Vegetales
14.
BMC Complement Med Ther ; 23(1): 49, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36793082

RESUMEN

BACKGROUND: Microencapsulation technology is the fundamental delivery system for encapsulating the natural bioactive compounds especially phenolic in order to developing bioavailability, stability and controlling release. This study was conducted to determine the antibacterial and health-promoting potential of the phenolic rich extract (PRE)-loaded microcapsules obtained from Polygonum bistorta root as a dietary phytobiotic in mice challenged by enteropathogenic Escherichia coli (E. coli). METHOD: The PRE was obtained from Polygonum bistorta root using fractionation by different polarity solvents and the highest PRE was encapsulated by the combination of modified starch, maltodextrin, and whey protein concentrate as wall materials using a spray dryer. Then, the physicochemical characterization (particle size, zeta potential, Morphology and polydispersity index) of microcapsules have been assessed. For the invivo study, 30 mice at five treatment were designed and antibacterial properties were analyzed. Furthermore, relative fold changes in the ileum population of E. coli was investigated using Real time PCR. RESULTS: The encapsulation of PRE resulted in the production of phenolic enriched extract-loaded microcapsules (PRE-LM) with a mean diameter of 330 nm and relatively high entrapment efficiency (87.2% w/v). The dietary supplementation of PRE-LM improved weight gain, liver enzymes, gene expression, morphometric characteristics of the ileum and decreased the population of E. coli present in the ileum significantly (p < 0.05). CONCLUSION: Our funding suggested PRE-LM as a promising phytobiotic against E. coli infection in mice.


Asunto(s)
Escherichia coli Enteropatógena , Infecciones por Escherichia coli , Polygonum , Animales , Ratones , Cápsulas , Composición de Medicamentos/métodos , Fenoles/química , Antibacterianos , Infecciones por Escherichia coli/tratamiento farmacológico
15.
Arch Med Sci ; 19(1): 203-208, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817686

RESUMEN

Introduction: MicroRNAs (miRNAs) are a class of gene expression epigenetic regulators that play roles in regulating genes involved in cholesterol homeostasis, including low-density lipoprotein receptor (LDLR) and PCSK9; therefore, miRNAs have been suggested as potential therapeutic targets for treating cardiometabolic disorders. Thus, the present study aimed to assess the effect of immunotherapy with the PCSK9 peptide vaccine on the hepatic expression levels of microRNAs associated with the LDLR pathway, including miRNA-27a, miRNA-30c, and miRNA-191, in normal vaccinated mice. Material and methods: PCSK9 immunogenic peptide and 0.4% alum adjuvant were mixed at a 1 : 1 ratio and used as a vaccine formulation. Male albino mice were randomly assigned to the vaccine or control group. Mice in the vaccine group were injected four times at two-week intervals with a PCSK9 peptide vaccine, and mice in the control group were injected with phosphate-buffered saline (PBS). Animal livers were sampled 2 weeks after the last injection to assess miRNA expression levels. The hepatic expression levels of miRNA-27a, miRNA-30c, and miRNA-191 were evaluated by SYBR Green real-time PCR, quantified by a comparative (2- Δ Δ CT) method (fold change (FC)) and normalized to U6 small nuclear RNA (U6snRNA) expression as an internal control. Results: The hepatic expression level of miRNA-27a was significantly lower in mice following immunotherapy with the PCSK9 peptide vaccine compared to the control group (FC: 0.731 ±0.1, p = 0.027). Also, there was a borderline significantly lower hepatic expression level of miRNA-30c in the vaccinated group compared to the control (FC: 0.569 ±0.1, p = 0.078). However, no significant differences were found in the hepatic expression level of miRNA-191 between the two studied groups (FC: 0.852 ±0.1, p = 0.343). Conclusions: According to the findings, the PCSK9 peptide vaccine could effectively reduce the hepatic expression level of miRNA-27a and may be helpful in the management of LDL-C level and atherosclerosis, which may be mediated through the LDLR pathway.

16.
Biotechnol Appl Biochem ; 70(1): 429-438, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35696633

RESUMEN

In the present research, we encapsulated a flavonoid called kaempferol into nanoliposomal structures and the health-promoting effects of synthesized nanoliposome-loaded kaempferol (NLK) were evaluated in mice challenged by cadmium-induced . The NLK characteristics, such as size, zeta potential, and polydispersity index, were 218.4 nm, -28.55 mV, and 0.29, respectively. The in vivo experiment revealed that the mice receiving water containing cadmium (2 mg/kg body weight/day) showed significant (p < 0.05) weight loss, an increase in liver enzyme activities, and hepatic oxidative stress. Dietary supplementation with NLK at concentrations of 2.5 and 5 mg/kg mice body weight notably (p < 0.05) improved the body weight, liver enzyme activities, hepatic oxidative stress, and antioxidant potential of the liver. Our findings elucidated that NLK could alleviate the toxicity of cadmium in mice challenged by cadmium-induced toxicity.


Asunto(s)
Cadmio , Quempferoles , Ratones , Animales , Cadmio/toxicidad , Cadmio/metabolismo , Quempferoles/farmacología , Hígado , Antioxidantes/farmacología , Estrés Oxidativo , Peso Corporal , Expresión Génica
17.
Biotechnol Appl Biochem ; 70(2): 790-797, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36059122

RESUMEN

Flavonoid compounds play an effective role in cancer suppression and today nanocarriers play an important role in improving the physicochemical properties and transmission of these compounds. In this study, polyethylene glycol-modified albumin nanoparticles were synthesized by desolvation method; after loading of naringenin (NRG), folic acid (FA) binding to the surface of nanoparticles was performed (BSA-PEG-FA-NG-NPs). The extent of NRG trapping and FA binding was assessed indirectly using UV absorption methods. The physicochemical properties of BSA-PEG-FA-NG-NPs were investigated by DLS, SEM electron microscopy, and FTIR methods, after which their effects were evaluated on the apoptosis mechanism via MTT, flow cytometry, and qPCR methods. The BSA-PEG-FA-NG-NPs with spherical morphology had dimensions of 205 nm with zeta-potential of 20.61 mV and dispersion index of 0.36. The NRG encapsulation was 84% and the FA binding was 75%. Anticancer effects of BSA-PEG-FA-NG-NPs were confirmed based on inhibiting breast cancer cells (IC50: 922 µg/ml), cell cycle arrest (SubG1 phase), and induction of apoptosis (upregulation of Caspase 3, 8, and 9).


Asunto(s)
Nanopartículas , Neoplasias , Albúmina Sérica Bovina/química , Línea Celular Tumoral , Ácido Fólico/farmacología , Ácido Fólico/química , Polietilenglicoles/química , Nanopartículas/química , Portadores de Fármacos/química
18.
Animals (Basel) ; 12(24)2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36552412

RESUMEN

Nasturtium officinale contains high amounts of phytochemical compounds that work against oxidative damages leading to improved health conditions in animals as well as humans. The study was performed to investigate the health benefits of nonencapsulated and nanoliposome-encapsulated phenolic rich fractions obtained from Nasturtium officinale on mice induced colorectal cancer. The experiment focused on encapsulation efficiency in improving the effectiveness of plant bioactive compounds. Phenolic rich fractions (PRF) were successfully loaded in the nanoliposome structure, a nanometer in size, of spherical shape and with homogeneous dispersion. Induction of colorectal cancer in mice impaired weight gain and feed intake, liver function and structural characteristics of ileum, while the dietary administration of nanoliposome-encapsulated PRF regulated the expression of Caspase 3, Bax, Bcl2, iNOS and SOD genes in the tumor tissue. The addition of nonencapsulated PRF and nanoliposome encapsulated PRF at the concentration of 100 mg TPC/kg BW/day improved the genes expression, although the nanoliposome-encapsulated PRF revealed better health outcomes compared to nonencapsulated PRF. Furthermore, both PRF improved intestinal morphology when the mice were challenged with colorectal cancer. The higher health promoting activity of nanoliposome-encapsulated PRF could be associated with its enhanced intestinal absorption, bioavailability, bioaccessibility and bioactivity. Consequently, the nanoliposome-encapsulated PRF could be considered as a promising anticancer agent against colorectal cancer.

19.
Food Sci Nutr ; 10(10): 3314-3322, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36249965

RESUMEN

Background: Artemisia aucheri contains antibacterial phenolic compounds. The current work was implemented to evaluate the effectiveness of a nanoliposome-encapsulated phenolic-rich fraction (PRF-NLs), as a dietary phytobiotic derived from Artemisia aucheri's areal parts, on the inhibition of enteropathogenic Campylobacter jejuni (C. jejuni) infection in mice. Methods: The phenolic-rich fraction was loaded into the nanoliposome structure to obtain a nanometer-scale size liposome with homogenous dispersion. Next, 40 white male balb/c mice were assigned to 4 treatment groups. The PRF-NLs antibacterial potential was evaluated by evaluating the blood parameters, liver lipid peroxidation, and gene expression profiling in the mice challenged by C. jejuni infection. Results: Mice infected by C. jejuni showed impairment in food intake, weight gain, liver function, ileum morphometric features, and ileum tissue inflammation. The diet of fortified food with the nonencapsulated and nanoliposome-encapsulated phenolic compounds was found to improve these parameters at 10 mg TPC/kg BW/day concentration. Our data indicated that the nanoliposome-encapsulated PRF was more effective in promoting the health parameters in mice as compared to nonencapsulated PRF. Conclusion: It could be concluded that the liposomal encapsulation can promote the solubility, availability, and effectiveness of Artemisia aucheri phenolic compounds playing a key role as phytobiotic in mice intervened by enteropathogenic C. jejuni.

20.
J Cell Mol Med ; 26(21): 5517-5527, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36226354

RESUMEN

In this study, nanoniosome-loaded Myristica fragrans' (MF) phenolic compounds (NLMP) were synthesized and characterized for their physical properties, and hepatoprotective effects on mice with liver toxicity induced by L-asparaginase (LA) injection. According to the results, NLMP has a spherical shape with a 263 nm diameter, a zeta potential of -26.55 mV and a polydispersity index (PDI) of 0.192. The weight and feed intake of mice induced with hepatotoxicity were significantly (p ≤ 0.05) increased after they were treated with NLMP (2.5 mg/kg body weight of mice). In addition, the blood levels of triglyceride (TG), cholesterol (Chol), liver enzymes (aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)) and total bilirubin were significantly (p ≤ 0.05) decreased. A significant increase (p ≤ 0.05) in the blood levels of the antioxidant defence system (glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)) were also reported after NLMP treatment. NLMP was also led to a significant decrease (p ≤ 0.05) in inflammatory-related gene expression of inducible nitric oxide synthase (iNOS) and Interferon-gamma (IFN-γ) in the liver, as well as a meaningful (p ≤ 0.05) increase in the expression of SOD as an antioxidant status biomarker. Consequently, the NLMP is recommended as a potential dietary supplement to alleviate the symptoms of LA-induced hepatotoxicity.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Myristica , Ratones , Animales , Myristica/metabolismo , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Aspartato Aminotransferasas , Fenoles/farmacología , Superóxido Dismutasa/metabolismo , Hígado/metabolismo , Extractos Vegetales/farmacología , Estrés Oxidativo
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