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1.
Cureus ; 16(7): e65354, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39184651

RESUMEN

Background Plant extracts, such as Echinacea, are preferred in the pharmaceutical industry for their natural availability and minimal adverse effects. Echinacea is known for its anti-inflammatory and other biological properties. Zinc oxide nanoparticles (ZnONPs) are cost-effective, safe, and easily synthesized, making them prominent in nanoparticle research. This study aims to determine the anti-inflammatory, cytotoxic, and antioxidant properties of ZnONPs synthesized using Echinacea. Methodology In this study, 5 mg of powdered Echinacea was mixed with 100 mL of distilled water, heated at 44°C until vaporization, cooled, and filtered twice. The extract was mixed with 0.1 g of zinc oxide and exposed to sunlight for two weeks for nanoparticle synthesis. After centrifugation at 3,500 rpm for eight minutes, nanoparticles were collected. Scanning electron microscope analysis was done to determine nanoparticle formation. Cytotoxicity analysis was conducted using the brine shrimp method, with surviving nauplii counted after exposure to different nanoparticle concentrations. Antioxidant activity was assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and ferric-reducing antioxidant power (FRAP) assay. Anti-inflammatory activity was assessed using membrane stabilization assay and bovine serum albumin (BSA) assay. Using SPSS Statistics Version 23 (IBM Corp., Armonk, NY, USA), the mean and standard deviation between the prepared extract and the standard were compared for all assays. Results In the cytotoxicity assessment, at 5 µL, the mortality of nauplii remained unchanged from the control. However, at 10 and 20 µL, a 10% increase in mortality was observed, which then stabilized at 40 and 80 µL with 20%. Regarding antioxidant activity, as nanoparticle concentration increased from 10 to 50 µL in the DPPH and FRAP assays, their effectiveness also increased accordingly. According to the anti-inflammatory assay, the membrane stabilization and BSA assay showed an increase in activity with increasing concentrations of 10 to 50 µL extract against similar concentrations of standard diclofenac sodium. Conclusions Echinacea-based ZnONPs demonstrated effective antioxidant and anti-inflammatory properties with low cytotoxicity, suggesting their potential use in future pharmaceutical or therapeutic applications.

2.
Sci Rep ; 14(1): 14769, 2024 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926533

RESUMEN

Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-ß-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-ß cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs' antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (- 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.


Asunto(s)
Antioxidantes , Silibina , Zeína , beta-Ciclodextrinas , Humanos , Zeína/química , Silibina/farmacología , Silibina/química , Células HT29 , beta-Ciclodextrinas/química , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/química
3.
Int Immunopharmacol ; 133: 112115, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38652959

RESUMEN

BACKGROUND: Human T cells play an important role in immunity against tuberculosis (TB) infection. Activating receptor HLA-DR and inhibitory receptor KLRG1 are critical regulators of T cell function during viral infection and tumorigenesis, but they have been less studied in TB infection. METHODS: In this study, we explored the relationship between CD3+ T cell expression of HLA-DR and KLRG1 receptors and function against TB infection. Flow cytometry was conducted to assess the immunomodulatory effects of HLA-DR and KLRG1 receptors on CD3+ T cells in patients with different TB infection status. RESULTS: We found activating receptors HLA-DR, NKG2C, CD57 and NKP46, and inhibitory receptors KLRG1 and KIR on CD3+ T cells in different TB infection status showed different distribution patterns; the cytotoxic potential and cytokine secretion capacity of CD3+ T cells after Mtb-specific antigen stimulation were significantly enhanced in TB infection groups. Further studies revealed HLA-DR+ T and KLRG1+ T cells expressed higher activating and inhibitory receptors than the negative population. In addition, the expression of cytotoxic potential and cytokine secretion capacity of HLA-DR+ T and KLRG1+ T cells was significantly higher than that of HLA-DR- T and KLRG1- T cells. CONCLUSIONS: Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in TB patients, suggesting CD3+ T cells expressing HLA-DR and KLRG1 are important effector cell phenotypes involved in the host anti-TB infection. HLA-DR and KLRG1 expressed by CD3+ T cells may be potential predictive markers of TB disease progression and clinical immune assessment.


Asunto(s)
Citocinas , Antígenos HLA-DR , Lectinas Tipo C , Receptores Inmunológicos , Tuberculosis , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Complejo CD3/metabolismo , Complejo CD3/inmunología , Células Cultivadas , Citocinas/metabolismo , Citotoxicidad Inmunológica , Antígenos HLA-DR/metabolismo , Antígenos HLA-DR/inmunología , Lectinas Tipo C/metabolismo , Mycobacterium tuberculosis/inmunología , Receptores Inmunológicos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Tuberculosis/inmunología
4.
Heliyon ; 10(6): e28092, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38533031

RESUMEN

Ubiquitination of RIPK1 plays an essential role in the recruitment of the IKK complex, an upstream component of pro-survival NF-κB. It also limits TNF-induced programmed cell death by inhibiting the spatial transition from TNFR1-associated complex-I to RIPK1-dependent death-inducing complex-II or necrosome. Thus, the targeted disruption of RIPK1 ubiquitination, which induces RIPK1-dependent cell death, has proven to be a useful strategy for improving the therapeutic efficacy of TNF. In this study, we found that eupatolide, isolated from Liriodendron tulipifera, is a potent activator of the cytotoxic potential of RIPK1 by disrupting the ubiquitination of RIPK1 upon TNFR1 ligation. Analysis of events upstream of NF-κB signaling revealed that eupatolide inhibited IKKß-mediated NF-κB activation while having no effect on IKKα-mediated non-canonical NF-κB activation. Pretreatment with eupatolide drastically interfered with RIPK1 recruitment to the TNFR1 complex-I by disrupting RIPK1 ubiquitination. Moreover, eupatolide was sufficient to upregulate the activation of RIPK1, facilitating the TNF-mediated dual modes of apoptosis and necroptosis. Thus, we propose a novel mechanism by which eupatolide activates the cytotoxic potential of RIPK1 at the TNFR1 level and provides a promising anti-cancer therapeutic approach to overcome TNF resistance.

5.
Cell Immunol ; 395-396: 104797, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38157646

RESUMEN

Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56. Bulk RNA sequencing of sorted Vδ2 cell fractions indicated that transcripts related to cytotoxic activity and NK function are enriched in the subset with the highest proportion of perforin+ cells. Among differentially expressed transcripts, IRF8, previously linked to CD8 T cell effector differentiation and NK maturation, has the potential to mediate Vδ2 cell differentiation towards cytotoxic effectors. Our current and past results support the hypothesis that distinct mechanisms regulate Vδ2 cell cytotoxic function before and after birth, possibly linked to different levels of microbial exposure.


Asunto(s)
Antígeno CD56 , Linfocitos T CD8-positivos , Citotoxicidad Inmunológica , Receptor de Muerte Celular Programada 1 , Receptores de Antígenos de Linfocitos T gamma-delta , Subgrupos de Linfocitos T , Humanos , Linfocitos T CD8-positivos/inmunología , Citocinas/metabolismo , Sangre Fetal , Perforina/genética , Perforina/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subgrupos de Linfocitos T/inmunología , Antígeno CD56/metabolismo
6.
Cureus ; 15(8): e44140, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37753020

RESUMEN

AIM: The aim of the study is to prepare the dual gel using nutmeg and Tulsi and then the evaluation of the antimicrobial properties and cytotoxic potential. MATERIALS AND METHODS: The Nutmeg Tulsi gel preparation has been done with a mixture of equal amounts of nutmeg and Tulsi powder. To the above-mentioned mixture, 5 mL of the concentrate is added and mixed thoroughly until the gel formation is done. The antimicrobial property is checked in the Porphyromonas gingivalis organism (p>0.05). The cytotoxic potential is checked in the Brine variety of the shrimp. The statistical analysis is done using a Paired t-test. RESULTS: The results stated that the Nutmeg Tulsi gel at a concentration of 100 microgram/mL showed a greater zone of inhibition (4.1±0.09 mm) when compared with doxycycline and has high antimicrobial potential in both Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Conclusion: The antimicrobial property of Nutmeg Tulsi gel has been demonstrated to be effective against P. gingivalis and A. actinomycetemcomitans. This suggests that it could be used as an affordable and effective "adjunct" alongside standard care for managing periodontal conditions.

7.
Plants (Basel) ; 12(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37050205

RESUMEN

The therapeutical attributes of silver nanoparticles (Ag-NPs) in both conditions (in vitro and in vivo) have been investigated using different plants. This study focused on the green chemistry approach that was employed to optimize the synthesis of silver nanoparticles (AgNPs) using Cleome brachycarpa aqueous extract as a reducing and stabilizing agent. The characterization of obtained CB-AgNPs was undertaken using UV-visible spectroscopy, Atomic-force microscopy (AFM), Fourier-Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), and Energy-Dispersive X-ray (EDX) analysis. Results suggest that CB-AgNPs synthesized via stirring produced small-sized particles with more even distribution. The synthesized silver nanoparticles were spherical with a 20 to 80 nm size range. In vitro studies were used to analyze antioxidant, antidiabetic, and cytotoxic potential under different conditions. The results also indicated that CB-AgNPs may have significant potential as an antidiabetic in low concentrations, but also exhibited potential antioxidant activity at different concentrations. Moreover, the anticancer activity against the breast cell line (MCF-7) with IC50 reached up to 18 µg/mL. These results suggest that green synthesized silver nanoparticles provide a promising phytomedicine for the management of diabetes and cancer therapeutics.

8.
Appl Biochem Biotechnol ; 195(2): 1197-1215, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36342622

RESUMEN

Leonotis nepetifolia (L.) R.Br. is a medicinally important herb belonging to the family Lamiaceae. The plant is typically found in tropical regions, and its leaf and root extracts are renowned for their ethno-botanical and therapeutic applications. This study was designed to determine the presence of various bioactive components, and to evaluate antibacterial, antifungal, antioxidant, and anti-proliferative activities. The preliminary phytochemical screening and gas chromatography-mass spectrometry (GC-MS) analysis of different solvent extracts revealed the presence of various bioactive compounds, of which methanol extract showed 24 compounds, petroleum ether extract revealed 26 compounds, and 24 compounds in hexane extracts. The major bioactive components including λ-sitosterol (16.20 %) in methanol extract, 1-nonadecanol (15.48 %) in petroleum extract, and eicosane (13.22 %) in hexane extract have been reported with various bio-therapeutic applications. In addition, the flower bud methanolic extract of L. nepetifolia exhibited inhibitory potential against all tested bacterial and fungal pathogens. The DPPH radical scavenging assay revealed that methanolic extract possessed the highest antioxidant activity. The scavenging activity increased in a concentration-dependent manner, as indicated by a 74 % inhibition rate at 1000 µg/ml. Furthermore, the in vitro cytotoxic effects of the methanolic extract on the HepG2 cell line were evaluated. The IC50 value of methanolic extract against HepG2 cells was determined to be 83.28 µg/ml. The findings reveal that different solvent extracts of L. nepetifolia flower buds contain a significant amount of various bioactive phytochemicals with antioxidant and anticancer activities; and thus, the plant could serve as a potential source of pharmacological applications.


Asunto(s)
Hexanos , Lamiaceae , Solventes , Cromatografía de Gases y Espectrometría de Masas , Metanol , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/química , Flores/química , Lamiaceae/química
9.
Life (Basel) ; 12(11)2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36431010

RESUMEN

Garcinia mangostana (Clusiaceae) is a rich pool of metabolites with diversified bioactivities. A new xanthone, garcixanthone E (1), and a new benzophenone, rhamnoside, as well as garcimangophenone C (9) together with garcinone E (2), α-mangostin (3), γ-mangostin (4), garcinone C (5), garcixanthone C (6), gartanin (7), and 2,4,6,3',5'-pentahydroxybenzophenone (8) were purified from G. mangostana EtOAc extract. Their structural verification was accomplished utilizing assorted spectral tools and relating to the literature. The in vitro cytotoxic potential versus MCF-7, A549, and HCT-116 cell lines demonstrated the moderate potential of 1 (IC50s 8.5, 5.4, and 5.7 µM, respectively) in comparison to doxorubicin (IC50s 0.18, 0.6 and 0.2 µM, respectively) using a sulforhodamine B (SRB) assay. Additionally, 1 and 9 had AAI (α-amylase inhibition) with IC50s 17.8 and 12.9 µM, respectively, compared to acarbose (IC50 6.7 µM). Further, their AAI mechanisms were inspected utilizing molecular-docking evaluation by employing the crystal structure of the human α-amylase (PDB-ID: 5EOF). Compound 9 possessed a reasonable docking score of -7.746 kcal/mol compared with the native ligand 7JR which had a docking score of -9.932 kcal/mol. These results could further provide new insight into the potential usage of G. mangostana as a functional food for regulating postprandial hyperglycemia via suppressing AA.

10.
Plants (Basel) ; 11(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35807645

RESUMEN

Photoprotective agents obtained from plants provide benefits for the health of the skin. The present study aims to assess the total phenolic content (TPC) and in vitro UV-protective properties of twelve essential oils (EOs) from plants grown in Colombia and to evaluate the antioxidant and cytotoxic potential of two species identified as photoprotective potentials: Cymbopogon flexuosus and Tagetes lucida. The composition of EOs was studied by GC/MS. The cytotoxicity of both EOs was examined using an MTT assay, and an H2-DCFDA probe was employed to estimate the intracellular production of ROS in HepG2 and Calu-1 cells. Major constituents (≥10%) were neral, geranial, geranyl acetate in C. flexuosus and estragole in T. lucida. The TPC for C. flexuosus and T. lucida EOs were ≥10 mg GAE/g of byproduct. Both EOs showed photoprotective properties (SPFin vitro: 13−14), and long-wavelength UVA protection (λc > 370 nm). HepG2 and Calu-1 cells exposed to C. flexuosus exhibited antiproliferative activity (˂50%) at 125 µg/mL, while T. lucida was at 250 and 500 µg/mL. The IC50 values for C. flexuosus were 75 and 100 µg/mL in HepG2 and Calu-1 cells, respectively, whereas those for T. lucida were >250 µg/mL. These EOs achieved significant inhibitory effects (between 15.6 and 40.4%) against H2O2-induced oxidative stress. The results showed that EO compounds recognized as antioxidants could counteract the effects elicited by H2O2.

11.
BMC Complement Med Ther ; 22(1): 30, 2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35101010

RESUMEN

BACKGROUND: Lactuca sativa is an edible plant commonly used by local communities to manage diabetes and stomach problems. METHODS: This work aimed to investigate the anti-oxidant, anticancer, antidiabetic and Anti-Alzheimer effects of hydroponically (HyL) and soil-grown (SoL) Lactuca sativa. Streptozotocin-induced diabetes and AlCl3-induced Alzheimer's disease model was used to evaluate the medicinal effects of Lactuca sativa. RESULTS: HyL showed significant activity in lipid peroxidation assay, DPPH and DNA protection assay, while SoL extract showed moderated activity, respectively. A similar activity response was quantified for α-glucosidase, α-amylase, acetylcholinesterase and butyrylcholinesterase inhibition assays. The cytotoxic potential of HyL and SoL extracts against MCF7, and HePG2 cancer cell lines exhibited significant activity. HyL and SoL showed a substantial decrease in blood glucose levels in streptozotocin-induced diabetic rats. Diabetes-related liver/kidney biomarkers and anti-oxidant enzyme trends moved toward normal after HyL and SoL treatment. In Anti-Alzheimer's based Morris water and elevated plus maze tests, HyL and SoL displayed memory-enhancing response and anti-anxiety behaviour, respectively. HPLC quantification of dopamine and serotonin revealed a moderate but significant (p<0.05) increase in the level of these neurotransmitters in HyL and SoL groups. CONCLUSION: Overall, the study revealed that hydroponic Lactuca sativa possesses the therapeutic potential to treat diseases like Alzheimer's and diabetes.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antineoplásicos/farmacología , Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Lactuca , Extractos Vegetales/farmacología , Animales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aprendizaje por Laberinto , Prueba del Laberinto Acuático de Morris , Pakistán , Ratas , Ratas Sprague-Dawley , Estreptozocina
12.
Drug Deliv Transl Res ; 12(6): 1521-1539, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34505271

RESUMEN

The key objective of the current research was to fabricate and optimize Capecitabine (Cap)-loaded [poly(lactic-co-glycolic acid)] PLGA-based nanoparticles (NPs) by enabling quality by design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA-based nanoparticles along with Eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box-Behnken design (BBD) was adopted to achieve the required critical quality attributes (CQAs), i.e., minimizing particle size, maximizing entrapment efficiency, and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines, and in vivo pharmacokinetic studies. The optimized PLGA-based nanoparticles were found to possess average particle size, PDI, zeta potential, and entrapment efficiency of 195 nm, 0.214, -6.65 mV, and 65%, respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Cap-loaded nanoparticles was found to be two fold increased than the pure drug, and also, it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay. The optimized PLGA-based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential as compared to pure drug.


Asunto(s)
Antineoplásicos , Nanopartículas , Antineoplásicos/farmacología , Capecitabina , Portadores de Fármacos , Liberación de Fármacos , Humanos , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solventes , Espectroscopía Infrarroja por Transformada de Fourier
13.
Antibiotics (Basel) ; 10(9)2021 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-34572710

RESUMEN

Ethnopharmacological approaches provide clues for the search of bioactive compounds. Dryopteris ramosa (Hope) C. Chr. (plant family: Dryopteridaceae) is an ethnomedicinal plant of the Galliyat region of Pakistan. The aqueous fraction (AqF) of D. ramosa is being used by inhabitants of the Galliyat region of Pakistan to treat their gastrointestinal tract ailments, especially those caused by bacteria. The aims of the present study were as follows: (i) to justify the ethnomedicinal uses of the AqF of D. ramosa; (ii) to isolate a bioactive compound from the AqF of D. ramosa; and (iii) to evaluate the antibacterial and cytotoxic potential of the isolated compound. Column chromatography (CC) techniques were used for the isolation studies. Spectroscopic techniques (UV-Vis, MS, 1&2D NMR) were used for structural elucidation. The agar-well diffusion method was used to evaluate the antibacterial potential of "i3CßDGP" against five bacterial strains, and compare it with the known antibiotic "Cefixime". The brine shrimp lethality test (BSLT) was used for cytotoxic studies. The AqF of D. ramosa afforded "iriflophenone-3-C-ß-D glucopyranoside (i3CßDGP)" when subjected to LH20 Sephadex, followed by MPLC silica gel60, and purified by preparative TLC. The "i3CßDGP" showed a strong potential (MIC = 31.1 ± 7.2, 62.5 ± 7.2, and 62.5 ± 7.2 µg/mL) against Klebsiella pneumoniae, Staphylococcus aureus, and Escherichia coli, respectively. On the other hand, the least antibacterial potential was shown by "i3CßDGP" (MIC = 125 ± 7.2 µg/mL), against Bacillus subtilis, in comparison to Cefixime (MIC = 62.5 ± 7.2 µg/mL). The cytotoxicity of "i3CßDGP" was significantly low (LD50 = 10.037 ± 2.8 µg/mL) against Artemia salina nauplii. This study not only justified the ethnomedicinal use of D. ramosa, but also highlighted the importance of ethnomedicinal knowledge. Further studies on AqF and other fractions of D. ramosa are in progress.

14.
Saudi J Biol Sci ; 28(5): 3031-3036, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34025179

RESUMEN

This research study is mainly focused to evaluate the anti-parasitic, insecticidal, cytotoxic and anti-alzheimer potential of various leaf extracts of Ajuga bracteosa Wallich ex Bentham. 04 different extracts were prepared using solvent of different polarity to determine the best candidate for potent bioactivity i.e. n-hexane (NH), Ethyl acetate (EA), Ethanol (EL) and Chloroform (CH). Concentrations of each extracts were made specified for all activities. All extracts were exploited for broad range of biomedical applications including leishmaniasis, in vitro anti-Alzheimer, insecticidal and cytotoxic studies. Our results showed that A. bracteosa n-hexane extract was highly active against Leishmania Tropica with significant inhibition of 58 ± 1.61 for promastigote and 63 ± 2.29 for amastigote at 1000 µg/mL. Furthermore, promising anti-alzheimer activity acetylcholinesterase (AChE) 46 ± 0.83 and butrylcholineterase (BChE) 49 ± 1.17 was noted for n-hexane. The insecticidal potential of these extracts were test against five different insects (Rhyzopertha dominica, Trogoderma granarium, Tribolium castaneum, Sitophilus oryze, and Callosobruchus analis). The higest mortality rate of insecticidal activity was recorded by n-hexane followed by Ethyl acetate whereas ethanol extract was found to be less effective against all the test species. Significant cytotoxic potential of each plant sample against Artemia salina thus aware us for further detailed research to find out novel drugs. Based on our results we believe that Ajuga bracteosa could be used to develop as a potential botanical insecticide against different insect and pests, such as aphids as well as an excellent source for the compound isolation as anti-tumor agent.

15.
Plants (Basel) ; 10(4)2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33810509

RESUMEN

Three specimens of H. officinalis subsp. aristatus were collected in three areas of the Abruzzo region (Italy) and subjected to macroscopic and microscopic observation to support their botanical identification. The essential oils (EOs) obtained from the aerial parts of the samples were characterized with the object to define their phytochemical and pharmaceutical biology profile. They highlight three different chemotypes, including one never seen in previous literature (CIV17-EO, distilled from sample harvested in 2017 at Civitaretenga), that showed a fingerprinting with the predominance of (-)-limonen-10-yl-acetate (67.9%). In 2017 European Food Safety Authority (EFSA) reported the genotoxicity of similar compounds, therefore, to dismiss any safety concern for the CIV17-EO use as flavouring substance, the Ames test was performed with no evidence of mutagenic activity. Safety of use coupled with chemical characterization of this new chemotype set the stage for a better standardization of H. officinalis EOs. The ethanolic extracts, on the other hand, with qualitatively similar chemical profiles in which caftaric, chlorogenic and rosmarinic acid were the main molecules, showed interesting antioxidant activity and a slight cytotoxicity towards the A549 cell line that could indicate a starting point for the evaluation of an additional preventive tool for maintaining health status.

16.
Cell Immunol ; 359: 104244, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33248366

RESUMEN

Human Vγ9Vδ2 T cells respond to several diverse pathogens by sensing microbial cholesterol intermediates. Unlike CD4 T cells, they are poised for rapid Th1-like responses even before birth, which allows them to play a key role in the first line of defense against pathogens in early life. However, their regulation and functional maturation during infancy (in particular the acquisition of cytotoxic potential) remain understudied. We thus characterized their responses to cholesterol intermediates and Bacille Calmette-Guérin in a cohort of African neonates and 12-month-old infants. Infant Vδ2 lymphocytes exhibited intermediate or adult-like expression of markers associated with differentiation or function, intermediate proliferative responses, and adult-like cytotoxic potential. The enhancement of Vδ2 cell cytotoxic potential coincided with decreasing PD-1 and increasing NKG2A expression. Our results are consistent with the hypothesis that switching from a PD-1+ to a NKG2A+ phenotype during infancy indicates a shift in mechanisms regulating Vδ2 T cell function.


Asunto(s)
Sangre Fetal/citología , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Adulto , Factores de Edad , Diferenciación Celular/fisiología , Células Cultivadas , Cordocentesis , Femenino , Expresión Génica/genética , Humanos , Lactante , Recién Nacido , Interferón gamma/metabolismo , Activación de Linfocitos/inmunología , Malaui/epidemiología , Masculino , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Receptor de Muerte Celular Programada 1/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Linfocitos T/inmunología
17.
Environ Res ; 191: 110134, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32860779

RESUMEN

The use of Filtering Respiratory Protective Devices (FRPD) is mandatory in Portugal to protect workers from the waste industry of harmful exposures. Deleterious health effects of exposure to bioburden via inhalation and/or ingestion include respiratory symptoms and nephrotoxicity. Between January and February 2019, 118 FRPD samples were collected in one waste sorting industry and characterized regarding microbial contamination and cytotoxicity, defined as cell metabolic activity, through the MTT colorimetric assay (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide). Cytotoxic effect was classified according to percentage of extinction values with respect to the control group, as follows: absent (≥90); low (80%-90%, +); medium (60%-79%, ++); and high (below 60%, +++). For 113 samples the MTT assay revealed a cytotoxic effect in A549 cells, of which 81 presented high cytotoxicity. In SK cells, a cytotoxic effect was observed in 56 samples, of which five displayed a high cytotoxic effect. Several moderate (p < 0.05) to strong (p < 0.01) correlations were found between higher bacterial and fungal counts both in interior layers (fungi and bacteria) and in exhalation valves (fungi) of FRPD samples and reduced cell metabolic activity of SK cells. On the basis of the obtained results for the cytotoxic effect of FRPD samples on two different cells lines, it was determined that A549 cells exhibited a cytotoxic effect for a higher number of FRPD, whereas the SK cells model correlated better with the other assessed parameters, namely, bacterial and fungal counts and conditions of FRPD use. Although the results are not conclusive on the most appropriate cell line to assess FRPD cytotoxicity, they reinforce the importance of in vitro toxicology in exposure assessments to determine the cytotoxicity of mixtures of contaminants, for better risk characterization and selection of appropriate risk management measures.


Asunto(s)
Dispositivos de Protección Respiratoria , Bacterias , Hongos , Humanos , Industrias , Portugal
18.
Curr Mol Med ; 19(9): 688-698, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31625470

RESUMEN

BACKGROUND: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. METHODS: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. RESULTS: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. CONCLUSION: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.


Asunto(s)
Glucosa/metabolismo , Peróxido de Hidrógeno/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Metformina/farmacología , Sirolimus/farmacología , Apoptosis/efectos de los fármacos , Glucemia , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Expresión Génica , Glucosa/farmacología , Humanos , Peróxido de Hidrógeno/farmacología , Células Madre Mesenquimatosas/citología , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo
19.
Toxicol Rep ; 6: 1086-1090, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31660295

RESUMEN

Globally, plant as herbal medicine is used to treat different diseases. The goal of this present study was to assess the antimicrobial and cytotoxic potential of ripe banana extracts with various polarities which were grown in Oman. The powder banana samples were extracted with methanol by soaking mode. The solvent was removed by a rotary evaporator and the extract was fractionated by dissimilar polarities of solvents to give corresponding extracts. The antimicrobial and cytotoxic potential of the various polarities extracts of ripe banana were determined by modifying disc diffusion and brine shrimp lethality (BSL) bioassays. Each banana extract at different concentrations showed modest antimicrobial potential against two Gram (+) and two Gram (-) with the range of inhibition 0-13 mm. The results of cytotoxic potential revealed that the each banana extract at various applied concentrations killed the shrimp larvae. Among the extracts, the butanol and water extract gave the maximum cytotoxic potential with LC50 value of 20.12 and 24.22 µg/ml, however, the lowest cytotoxic potential was obtained in the ethyl acetate extract with LC50 value of 36.68 and 49.32 µg/ml. In our experimental results showed that the highest polarity banana extracts have significant antimicrobial and cytotoxic potential. In conclusion, the highest polarity extract could be a candidate for the use of antibiotics.

20.
Toxicon ; 168: 22-31, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31233771

RESUMEN

This study was conducted to examine the cytotoxic effects of Nubein6.8 isolated from the venom of the Egyptian Spitting Cobra Naja nubiae on melanoma (A375) and ovarian carcinoma cell lines and to reveal its mode of action. The size of Nubein6.8 (6801.8 Da) and its N-terminal sequence are similar to cytotoxins purified from the venom of other spitting cobras. Nubein6.8 showed a high significant cytotoxic effect on A375 cell line and moderate effect on A2780. A clonogenic assay showed that Nubein6.8 has a significant long-term potency on A375 cell survival when compared to A2780. The molecular intracellular signaling pathways of Nubein6.8 have been investigated using Western blotting analysis, flow cytometry, and microscale protein labeling. This data revealed that Nubein6.8 has DNA damaging effects and the ability to activate apoptosis in both tumor cell lines. Cellular uptake recordings revealed that the labeled-Nubein6.8 was intracellularly present in A375 cells while A2780 displayed resistance against it. SEM examination showed that Nubein6.8 was found to have high accessibility to malignant melanoma cells. The apoptotic effect of Nubein6.8 was confirmed by TEM examination that revealed many evident characteristics for Nubein6.8 apoptotic efficacy on A375 cell sections. Also, TEM reflected many resistant characteristics that faced Nubein6.8 acquisition through ovarian carcinoma cell sections. Accordingly, the snake venom peptide of Nubein6.8 is a promising template for developing potential cytotoxic agents targeting human melanoma and ovarian carcinoma.


Asunto(s)
Antineoplásicos/química , Venenos Elapídicos/química , Venenos Elapídicos/toxicidad , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayo de Unidades Formadoras de Colonias , Daño del ADN/efectos de los fármacos , Venenos Elapídicos/metabolismo , Humanos , Naja , Neoplasias/tratamiento farmacológico , Péptidos/química , Péptidos/metabolismo , Péptidos/toxicidad , Transducción de Señal
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