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1.
RSC Adv ; 14(12): 8583-8601, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38487521

RESUMEN

Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes hazardous effects. Herein, titanium dioxide (TiO2) NPs were bioengineered using a novel and facile ultrasound-assisted approach utilizing the greenly extracted essential oil of Ocimum basilicum. FTIR and UV-Vis spectrophotometry were used to confirm the formation of TiO2 NPs. The X-ray diffraction (XRD) analysis showed the crystalline nature of TiO2 NPs. TEM analysis revealed the spherical morphology of the NPs with sizes ranging from 5.55 to 13.89 nm. Energy-dispersive X-ray (EDX) confirmed the purity of the greenly synthesized NPs. TiO2 NPs demonstrated outstanding antitumor activity against breast (MCF-7) and lung (A-549) cancer cells with estimated IC50 values of 1.73 and 4.79 µg mL-1. The TiO2 NPs were cytocompatible to normal cells (MCF-10A) with a selectivity index (SI) of 8.77 for breast and 3.17 for lung cancer. Biological assays revealed a promising potential for TiO2 NPs to induce apoptosis and arrest cells at the sub-G1 phase of the cell cycle phase in both cancer cell lines. Molecular investigations showed the ability of TiO2 NPs to increase apoptotic genes' expression (Bak and Bax) and their profound ability to elevate the expression of apoptotic proteins (caspases 3 and 7). Molecular docking demonstrated strong binding interactions for TiO2 NPs with caspase 3 and EGFR-TK targets. In conclusion, the greenly synthesized TiO2 NPs exhibited potent antitumor activity and mitochondrion-based cell death against breast and lung cancer cell lines while maintaining cytocompatibility against normal cells.

2.
Int J Biol Macromol ; 263(Pt 1): 130694, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458284

RESUMEN

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.


Asunto(s)
Melanoma , Nanopartículas del Metal , Neoplasias Cutáneas , Óxido de Zinc , Animales , Humanos , Óxido de Zinc/farmacología , Óxido de Zinc/química , Espectroscopía Infrarroja por Transformada de Fourier , Melanoma/tratamiento farmacológico , Albúmina Sérica Bovina/química , Neoplasias Cutáneas/tratamiento farmacológico , Estrés Oxidativo , Antibacterianos/farmacología , Nanopartículas del Metal/química , Extractos Vegetales/química
3.
Front Oncol ; 13: 1221275, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37706181

RESUMEN

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.

4.
Asian Pac J Cancer Prev ; 24(8): 2629-2639, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37642048

RESUMEN

The present study aimed to investigate the potential inhibitory activities of various Terminalia brownie extracts against the proliferation of different cancer cell lines. Fractionation was carried out through the process of liquid-liquid extraction produced four fraction types using polarity-enhancing solvents such as, n-hexane, chloroform, ethyl acetate, and water. All extracts have been tested for their cytotoxicity against cancer cell lines using SRB assay and their inhibitory activity on cell cycle phases using flow cytometry. The chloroform extract exhibited a cytotoxic effect against all three types of cancer cell lines and especially the HepG2 cells at 100-µg concentration. Moreover, the most prominent plant extracts of chloroform, acetyl acetate, and hexane showed significant induction of cell death during the S phase cell cycle. The findings of this study suggest that compounds in the Terminalia brownie plant used in traditional Saudi medicine may have the potential to suppress the growth of cancer cell lines.


Asunto(s)
Neoplasias , Terminalia , Humanos , Cloroformo , Línea Celular , Extractos Vegetales/farmacología , Neoplasias/tratamiento farmacológico
5.
Environ Sci Pollut Res Int ; 30(60): 125197-125213, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37482589

RESUMEN

The prevalence of organic solid waste worldwide has turned into a problem that requires comprehensive treatment on all fronts. The amount of agricultural waste generated by agro-based industries has more than triplet. It not only pollutes the environment but also wastes a lot of beneficial biomass resources. These wastes may be utilized as a different option/source for the manufacturing of many goods, including biogas, biofertilizers, biofuel, mushrooms and tempeh as the primary ingredients in numerous industries. Utilizing agro-industrial wastes as good raw materials may provide cost reduction and lower environmental pollution levels. Agro-industrial wastes are converted into biofuels, enzymes, vitamin supplements, antioxidants, livestock feed, antibiotics, biofertilizers and other compounds via solid-state fermentation (SSF). By definition, SSF is a method used when there is little to no free water available. As a result, it permits the use of solid materials as biotransformation substrates. Through SSF methods, a variety of microorganisms are employed to produce these worthwhile things. SSFs are therefore reviewed and discussed along with their impact on the production of value-added items. This review will provide thorough essential details information on recycling and the use of agricultural waste.


Asunto(s)
Agricultura , Residuos Industriales , Fermentación , Residuos Industriales/análisis , Residuos Sólidos , Biocombustibles
6.
BMC Complement Med Ther ; 23(1): 164, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37210476

RESUMEN

BACKGROUND: The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity. METHODS: First, HPLC-PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity. RESULTS: HPLC-PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology. CONCLUSION: Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Jasminum , Humanos , Femenino , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Farmacología en Red , Antineoplásicos/farmacología , Flores , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptores ErbB
7.
BMC Complement Med Ther ; 23(1): 167, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37217985

RESUMEN

BACKGROUND: Viscum orientale is a largely used parasitic plant with traditional medicinal properties. They are considered to possess the medicinal properties of host tree which they grow on. It's a least explored plant with ethanopharmacological importance. As a result, the current work aimed to investigate the biological effects of Viscum orientale extract and silver nanoparticles (AgNPs) generated from it. METHODS: AgNPs synthesized using Viscum orientale plant extract and analysed on time dependent series and was characterized using Ultra Violet UV-visible spectra, Fourier Transform Infrared Spectroscopy FTIR, X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM). Further using disc method anti-microbial assay was performed following antioxidation screening using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and nitric oxide content and heamgglutination with human blood. RESULTS: On green synthesis using silver, the phyto contituents of plant Viscum orientale effectively reduced silver ions at 3-4 h of continuous stirring to form AgNPs. UV-vis spectra showed a typical peak of AgNPs at 480 nm. The FTIR analysis confirmed the covering of silver layers to bio-compounds of the extract. SEM analysis represented AgNPs as spherical morphologies ranging from 119-222 nm. AgNPs exhibited impressive zone of inhibition against Escherichia coli (8.1 ± 0.3 mm), Staphylococcus aureus (10.3 ± 0.3 mm), Bacillus subtilis (7.3 ± 0.3 mm), Bacillus cereus (8.2 ± 0.3 mm), Salmonella typhi (7.1 ± 0.2 mm). AgNps exhibited efficiency against DPPH at EC50 value of 57.60 µg/ml. and reducing power at EC50 of 53.42 µg/ml and nitric oxide scavenging of EC50 of 56.01 µg/ml concentration. Further, anthelmintic activity results showed synthesized nanoparticles significant reduction in the paralysis time to 5.4 ± 0.3 min and death time to 6.5 ± 0.6 min in contrast to the individual factors. On hemagglutination using AgNPs, above 80 µg/ml of concentration showed very significant effect on comparison with water extract. CONCLUSION: Synthesized AgNPs using Viscum orientale water extract displayed versatile biological activity than individual extract. This study has forecasted a new path to explore more on this AgNPs for further research.


Asunto(s)
Antihelmínticos , Antiinfecciosos , Nanopartículas del Metal , Humanos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Óxido Nítrico , Antiinfecciosos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química
8.
Chemosphere ; 324: 138311, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36878368

RESUMEN

A novel kinetic model has been developed to explain the degradation of total petroleum hydrocarbons. Microbiome engineered biochar amendment may result in a synergistic impact on degradation of total petroleum hydrocarbons (TPHs). Therefore, the present study analyzed the potential of hydrocarbon-degrading bacteria A designated as Aeromonas hydrophila YL17 and B as Shewanella putrefaciens Pdp11 morphological characterized as rod shaped, anaerobic and gram-negative immobilized on biochar, and the degradation efficiency was measured by gravimetric analysis and gas chromatography-mass spectrometry (GC-MS). Whole genome sequencing of both strains revealed the existence of genes responsible for hydrocarbon degradation. In 60 days remediation setup, the treatment consisting of immobilization of both strains on biochar proved more efficient with less half-life and better biodegradation potentials compared to biochar without strains for decreasing the content of TPHs and n-alkanes (C12-C18). Enzymatic content and microbiological respiration showed that biochar acted as a soil fertilizer and carbon reservoir and enhanced microbial activities. The removal efficiency of hydrocarbons was found to be a maximum of 67% in soil samples treated with biochar immobilized with both strains (A + B), followed by biochar immobilized with strain B 34%, biochar immobilized with strain A 29% and with biochar 24%, respectively. A 39%, 36%, and 41% increase was observed in fluorescein diacetate (FDA) hydrolysis, polyphenol oxidase and dehydrogenase activities in immobilized biochar with both strains as compared to control and individual treatment of biochar and strains. An increase of 35% was observed in the respiration rate with the immobilization of both strains on biochar. While a maximum colony forming unit (CFU/g) was found 9.25 with immobilization of both strains on biochar at 40 days of remediation. The degradation efficiency was due to synergistic effect of both biochar and bacteria based amendment on the soil enzymatic activity and microbial respiration.


Asunto(s)
Microbiota , Petróleo , Contaminantes del Suelo , Petróleo/análisis , Suelo/química , Contaminantes del Suelo/análisis , Microbiología del Suelo , Hidrocarburos/metabolismo , Biodegradación Ambiental , Bacterias/genética , Bacterias/metabolismo
9.
Front Chem ; 11: 1114109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36817178

RESUMEN

Introduction: The use of plant extracts in the green synthesis of metallic nanoparticles is one of the simplest, most practical, economical, and ecologically friendly methods for avoiding the use of toxic chemicals. Method: Silver nanoparticles (AgNPs) were synthesized, employing a high-efficiency, non- toxic, cost-effective, green, and simple technique that included the use of Salacia oblonga root extract (SOR) as a capping agent compared to synthetic nanoparticles. The use of S. oblonga can be seen in traditional medicines for treating diabetes, obesity, rheumatism, gonorrhea, asthma, and hyperglycemia. The objectives of the current study were to green synthesize S. oblonga root extract silver nanoparticles (SOR-AgNPs), characterize them, and study their antioxidant, antibacterial, and antidiabetic activities. Result: The shape of SOR-AgNPs was spherical, at less than 99.8 nm in size, and exhibited a crystalline peak at XRD. The green synthesized SOR-AgNPs showed significant antioxidant properties like DPPH (80.64 µg/mL), reducing power capacity (81.09 ± SEM µg/mL), nitric oxide (96.58 µg/mL), and hydroxyl (58.38 µg/mL) radical scavenging activities. The MIC of SOR-AgNPs was lower in gram-positive bacteria. The SOR-AgNPs have displayed efficient inhibitory activity against α-amylase, with an EC50 of 58.38 µg/mL. Analysis of capping protein around the SOR-AgNPs showed a molecular weight of 30 kDa. Discussion: These SOR-AgNPs could be used as antibacterial and antidiabetic drugs in the future as it is cheap, non-toxic, and environmentally friendly. Bio-fabricated AgNPs had a significant impact on bacterial strains and could be used as a starting point for future antibacterial drug development.

10.
Molecules ; 27(23)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36500380

RESUMEN

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Simulación del Acoplamiento Molecular , Proteasas 3C de Coronavirus , Simulación de Dinámica Molecular , Inhibidores de Proteasas/farmacología
11.
Biomed Pharmacother ; 143: 112220, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34649349

RESUMEN

This study aimed to evaluate and compare the therapeutic effect of camel milk exosomes derived from colostrum, early, mid, and late lactation periods on liver cancer HepaRG cells. These exosomes showed cytotoxicity on HepaRG while being safer on normal human liver THLE-2 cells. Among the four different isolated exosome groups, exosomes isolated from colostrum exhibited the highest apoptotic potential on HepaRG as indicated by highest DNA damage and upregulated expression of Bax and caspase3 expression, but with lowest Bcl2 expression. HepaRG-treated with colostrum-derived exosomes also exhibited the lowest expression of inflammation-related genes (TNFα, NFkB, TGFß1, and Cox2) and the angiogenesis-related gene VEGF. Colostrum-derived exosomes had significantly higher expression of lactoferrin and kappa casein than other milk-derived exosomes. These results indicate that colostrum-derived exosomes have a more potent anti-cancer effect on HepaRG cells than exosomes derived from the early, mid, and lat lactation periods. This effect could be mediated through induction of apoptosis and inhibition of inflammation and angiogenesis. Therefore, these exosomes could be used as safe adjuvants/carriers to deliver chemotherapeutics and to potentiate their anticancer effect on liver cancer cells.


Asunto(s)
Apoptosis , Camelus , Carcinoma Hepatocelular/terapia , Calostro/metabolismo , Exosomas/metabolismo , Mediadores de Inflamación/metabolismo , Neoplasias Hepáticas/terapia , Neovascularización Patológica , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Humanos , Lactancia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Molecules ; 25(24)2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33322431

RESUMEN

Diabetes is a major health problem that is associated with high risk of various complications. Medicinal plants hold great promise against diabetes. The traditional use of Cleome droserifolia as an antidiabetic agent was correlated to its flavonol glycosides content. In the current study, five major flavonol glycosides appeared on the RP-HPLC chromatogram of the aqueous extract namely; quercetin-3-O-ß-d-glucosyl-7-O-α-rhamnoside (1), isorhamnetin-7-O-ß-neohesperidoside (2), isorhamnetin-3-O-ß-d-glucoside (3) kaempferol-4'-methoxy-3,7-O-α-dirhamnoside (4), and isorhamnetin-3-O-α-(4″-acetylrhamnoside)-7-O-α-rhamnoside (5). The inhibitory activities of these compounds were tested in vitro against several enzymes involved in diabetes management. Only the relatively less polar methoxylated flavonol glycosides (4, 5) showed mild to moderate α-amylase and α-glucosidase inhibitory activities. Compounds 1-4 displayed remarkable inhibition of dipeptidyl peptidase IV (DPPIV) enzyme (IC50 0.194 ± 0.06, 0.573 ± 0.03, 0.345 ± 0.02 and 0.281 ± 0.05 µg/mL, respectively) comparable to vildagliptin (IC50 0.154 ± 0.02 µg/mL). Moreover, these compounds showed high potential in preventing diabetes complications through inhibiting aldose reductase enzyme and combating oxidative stress. Both isorhamnetin glycoside derivatives (2, 3) exhibited the highest activities in aldose reductase inhibition and compound 2 (IC50 5.45 ± 0.26 µg/mL) was even more potent than standard quercetin (IC50 7.77 ± 0.43 µg/mL). Additionally, these flavonols exerted excellent antioxidant capacities through 2, 2-diphenyl-1-picrylhydrazil (DPPH) and ferric reducing antioxidant (FRAP) assays.


Asunto(s)
Dipeptidil Peptidasa 4/química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Glicósidos/farmacología , Aldehído Reductasa/química , Aldehído Reductasa/metabolismo , Antioxidantes/química , Compuestos de Bifenilo/química , Química Farmacéutica/métodos , Cromatografía Líquida de Alta Presión , Cleome , Diseño de Fármacos , Depuradores de Radicales Libres , Humanos , Hipoglucemiantes , Técnicas In Vitro , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Modelos Químicos , Estrés Oxidativo , Picratos/química , Vildagliptina/farmacología , alfa-Amilasas/química , alfa-Glucosidasas/metabolismo
13.
Biomed Pharmacother ; 124: 109841, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31972360

RESUMEN

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats' testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC50) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.


Asunto(s)
Antiparasitarios/toxicidad , Ivermectina/farmacología , Testículo/efectos de los fármacos , Vitamina E/farmacología , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Sinergismo Farmacológico , Fertilidad/efectos de los fármacos , Ivermectina/administración & dosificación , Ivermectina/análogos & derivados , Ivermectina/toxicidad , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Selenio/toxicidad , Testículo/patología , Vitamina E/administración & dosificación
14.
Int J Biol Macromol ; 165(Pt B): 2750-2764, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33736280

RESUMEN

A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to encapsulate this macromolecular complex, targeting enhancing its therapeutic effect and minimizing its side impacts. The encapsulated Ag(I) complex was significantly triggered apoptosis (P < 0.05) with much more rapidly release of Ag(I)FLLL49-GbA from the CNPs at pH 5.3 than at pH 7.4, which is beneficial for cancer-targeted drug delivery. Free complex showed promising ability in preventing glucose uptake and lactate production coupled with cellular ATP depletion in cancer cells. Additionally, there was significant decrease in the inflammatory cytokines in breast cancer (MCF-7) and lung cancer (A549) cells with values of P < 0.01 and P < 0.001 after 24 h incubation. Furthermore, the death-inducing proteins have been significantly up-regulated (P < 0.01 to P < 0.001) after 36 h incubation of cancer cells. Consequently, the novel curcuminoid macromolecule showed significant feasibility in triggering the high expression of apoptotic caspases caspase 3, caspase 8, P53, and Bax (P < 0.01 to P < 0.001) after 48 h of chemotherapy. Noteworthy, the cytotoxicity of Ag(I)FLLL49-GbA was significantly increased toward cancer cells (MCF-7 > A549), while, reduced toward normal cells (HeLa) after loading on chitosan Nano-vehicles.


Asunto(s)
Antineoplásicos/farmacología , Quitosano/química , Diarilheptanoides/farmacología , Neoplasias/metabolismo , Plata/farmacología , Células A549 , Antineoplásicos/química , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Diarilheptanoides/química , Sistemas de Liberación de Medicamentos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Células MCF-7 , Nanopartículas , Neoplasias/tratamiento farmacológico , Plata/química , Regulación hacia Arriba
15.
Nat Prod Res ; 34(15): 2167-2172, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30835538

RESUMEN

The CHCl3 fraction of MeOH extract of Periploca somaliensis (family Asclepiadaceae) fruits afforded a new scalarane sesterterpene, namely perisomalien A (1), along with lupeol acetate (2), ß-amyrin (3), cycloart-23Z-ene-3ß,25-diol (4), and ß-sitosterol-3-O-ß-D-glucopyranoside (5). Their chemical structures were established by various spectroscopic analyses, in addition to comparison with the formerly reported data. Moreover, the cytotoxic activity of these metabolites was assessed towards MCF-7, HepG2, and HCT-116 tumour cell lines using sulforhodamine B (SRB) assay. Compound 4 showed the most potent cytotoxic profile with IC50 9.0 µM towards MCF-7, compared to doxorubicin (IC50 0.18 µM). Also, 1 and 4 possessed the most potent effect towards HepG2 with IC50s 26.7 and 25.9 µM, respectively. In addition, all tested compounds showed cytotoxic effects with IC50 values ranging from 19.9 to 39.3 µM against HCT-116.


Asunto(s)
Periploca/química , Extractos Vegetales/química , Sesterterpenos/química , Sesterterpenos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Frutas/química , Humanos , Concentración 50 Inhibidora , Magnoliopsida , Ácido Oleanólico/farmacología , Triterpenos Pentacíclicos/aislamiento & purificación , Extractos Vegetales/farmacología , Sesterterpenos/aislamiento & purificación
16.
Molecules ; 24(3)2019 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-30708938

RESUMEN

Natural products, especially secondary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. Aeluropus lagopoides is one of the common halophyte plants that survive under stressed conditions, and has been used for healing wounds and as a painkiller. The bioactivity and the chemical composition of this plant have been poorly investigated. Consequently, the chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), and n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites were evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using a SulphoRhodamine-B (SRB) test. Their mechanisms of action were verified by observing the appearance of apoptotic bodies using the fluorescent microscope, while their antiproliferative impacts were evaluated using a flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate had the highest cytotoxicity and thus the greatest anticancer activity effect on HepG2 with IC50 (24.29 ± 0.85 and 11.22 ± 0.679 µg/mL, respectively). On the other hand, flow cytometer results showed that secondary metabolites could inhibit the cell cycle in the G0/G1 phase. To ascertain the chemical composition⁻function relationship, the extracts were analyzed using LC-MS/MS. Accordingly, A. lagopoides hexane and ethyl acetate extracts may contain agents with anticancer potential.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Poaceae/química , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida , Neoplasias del Colon , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Neoplasias Hepáticas , Masculino , Microscopía Fluorescente , Extractos Vegetales/química , Espectrometría de Masas en Tándem
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