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1.
Comput Biol Med ; 135: 104555, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144270

RESUMO

BACKGROUND: Non-structural protein 1 (Nsp1), a virulence agent of SARS-CoV-2, has emerged as an important target for drug discovery. Nsp1 shuts down the host gene function by associating with the 40S ribosomal subunit. METHODS: Molecular interactions, drug-likeness, physiochemical property predictions, and robust molecular dynamics (MD) simulations were employed to discover novel Nsp1 inhibitors. In this study, we evaluated a series of molecules based on the plant (Cedrus deodara) derived α,ß,γ-Himachalenes scaffolds. RESULTS: The results obtained from estimated affinity and ligand efficiency suggested that BCH10, BCH15, BCH16, and BCH17 could act as potential inhibitors of Nsp1. Moreover, MD simulations comprising various MD driven time-dependent analyses and thermodynamic free energy calculations also suggested stable protein-ligand complexes and strong interactions with the binding site. Furthermore, the selected molecules passed drug likeliness parameters and the physiochemical property analysis showed acceptable bioactivity scores. CONCLUSION: The structural parameters of dynamic simulations revealed that the reported molecules could act as lead compounds against SARS-CoV-2 Nsp1 protein.


Assuntos
Cedrus/química , Compostos Fitoquímicos/farmacologia , RNA Polimerase Dependente de RNA/antagonistas & inibidores , SARS-CoV-2 , Proteínas não Estruturais Virais/antagonistas & inibidores , Sítios de Ligação , RNA Polimerase Dependente de RNA/química , Subunidades Ribossômicas Menores de Eucariotos , Proteínas não Estruturais Virais/química
2.
J Food Sci ; 86(7): 2910-2923, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34147039

RESUMO

The effect of pine needle extract from Cedrus deodara (PNE) on the quality of salted meat was reported, and its action mechanism was further investigated. With the treatment of PNE, the physicochemical properties of salted meat were improved. The peroxide value decreased from 16.18 to 6.78 mmol O2 /kg, while the thiobarbituric acid value decreased from 0.79 to 0.40 mg MDA/kg. Moreover, the salted meat with PNE also had the better texture, color, and volatile compositions. The 0.2% PNE group showed the highest ΔE value (63.16 ± 0.56), hardness (813.5 ± 48.7 g), and volatility (45.86 ± 0.39), while the control group showed the lowest ΔE value (43.92 ± 2.13), hardness (515.8 ± 17.3 g) and volatility (29.97 ± 0.56). In addition, with the analysis of fluorescence and circular dichroism spectroscopy, the spatial structures of myofibrillar protein (MP) in salted meat were obviously changed by PNE. Meanwhile, methylconiferin, 1-O-feruloyl-ß-D-glucose, nortrachelogenin, secoxyloganin, 1-O-(4-coumaroyl)-ß-D-glucose and pelargonidin-3-O-glucoside were identified from PNE. Furthermore, according to the analysis of molecular docking, hydrogen bond, hydrophobic force, and electrostatic force were obtained as the main molecular forces between MP and the phenolic compounds of PNE, while arginine, glutamic acid, and glycine residues were the main binding sites. All results suggested that PNE might be a potential candidate to improve the quality of salted meat in the food industry. PRACTICAL APPLICATION: The quality deterioration of meat may not only affect its further processing and consumption but also may lead to some food safety problems. In present study, PNE exhibited the fine capability to inhibit the oxidation of meat, while it could ameliorate the texture, color, and physicochemical properties of meat due to its tightly interaction with myofibrillar protein. All result suggested that PNE could be potentially utilized to improve the quality of meat in food industry.


Assuntos
Cedrus/química , Conservantes de Alimentos/farmacologia , Qualidade dos Alimentos , Carne/análise , Extratos Vegetais/farmacologia , Sensação , Cloreto de Sódio/química , Animais , Conservantes de Alimentos/química , Humanos , Simulação de Acoplamento Molecular , Extratos Vegetais/química
3.
Environ Sci Pollut Res Int ; 28(39): 55446-55453, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132963

RESUMO

Air pollution is becoming increasingly dangerous which is quite a significant issue of today's world, especially air pollution from heavy metal, whose emission increases with industrial and traffic activities. This is of great importance in terms of environmental pollution and human health. Heavy metals do not deteriorate and disappear easily on earth. They are liable to bioaccumulate within cells in organisms. Most of them demonstrate harmful effects in addition as a result of advanced accumulation, and thus they emerge as toxic and carcinogenic. Therefore, it is of great importance to observe the changes in heavy metal concentrations in the air. One of the most effective techniques for monitoring the change of heavy metal concentrations in the atmosphere is the use of annual rings of trees as biomonitors. In this study, in the annual rings of the Cedrus atlantica Manetti tree cut at the Kastamonu province at the end of 2019, the variation of the concentrations of some of the heavy metals most associated with traffic density was tried to be determined. Within the scope of the study, Cr and Mn concentration in the outer bark and the inner bark was compared with the direction and wood for the variation of heavy metal concentrations. Also, variance analysis and Duncan test were applied and evaluated. As a result of the study, while the highest values in many heavy metals are generally obtained in the outer bark, the transfer of metals in the wood is limited, and some heavy metal concentrations change significantly depending on the direction, especially in the wood. This change is related to the traffic density, so Cedrus atlantica Manetti annual rings are very suitable as biomonitors for air pollution control.


Assuntos
Poluentes Atmosféricos/análise , Cedrus , Monitoramento Biológico , Cedrus/metabolismo , Humanos
4.
Int J Med Sci ; 18(11): 2417-2430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967620

RESUMO

Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G0/G1 phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Cedrus/química , Glioblastoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Camundongos , Extratos Vegetais/uso terapêutico , Ratos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Bull Entomol Res ; 111(5): 579-584, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33998423

RESUMO

Temperature is one of the main factors affecting insect growth, development and reproduction. The effects of temperatures (10, 15, 20, 25 and 30°C) on the development and reproduction of Cinara cedri Mimeur (Hemiptera: Aphidoidea: Lachnidae) fed on Cedrus deodara (Roxb.) G. Don were evaluated in this study. With the increase of temperature from 10 to 30°C, the development duration at different development stages gradually shortened. There was a significant positive correlation between the developmental rates and temperature, following a quadratic regression model. The lower developmental threshold temperature (C) and effective accumulated temperatures (K) for completing a generation were 4.13°C and 263.4 degree-days, respectively. The highest fecundity was observed at 20°C with 25.74 first-instar nymphs/female. Both the highest intrinsic rate of increase (r, 0.11 ± 0.03) and net reproduction rate (R0, 19.06 ± 2.05) were observed at 20°C, whereas the lowest values of r (0.05 ± 0.01) at 10°C and R0 (5.78 ± 0.88) at 30°C were observed. The results suggest that temperature significantly affects the biology of C. cedri and the optimal temperature for its development is 20°C.


Assuntos
Hemípteros/crescimento & desenvolvimento , Temperatura , Animais , Cedrus , Fertilidade/fisiologia , Hemípteros/fisiologia , Estágios do Ciclo de Vida
6.
Bioorg Chem ; 112: 104860, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33839462

RESUMO

Benzosuberene-sulfone (BSS) analogues have been semi-synthesized following green approaches from himachalenes, which has been extracted from essential oil of Cedrus deodara. In this process, benzosuberene in presence of different aryl or alkyl sodium sulfinates, I2 and potassium persulfate (K2S2O8) in acetonitrile-water solvent conditions gave BSS-analogues at room temperature. Under this reaction, a facile endocyclic ß-H elimination has been noticed for BSS-analogues synthesis instead of vinyl sulfones and the reason may be due to its specific structure and electronic environment. The BSS-compounds were obtained with moderate to excellent yields under mild conditions. All the compounds were computationally subjected to drug likeliness and toxicity prediction studies. Further, the synthesized molecules were evaluated under in-silico studies for their binding affinity towards the native Peroxisome Proliferator-Activated Receptor Gamma (PPARG), and two PPARG mutants (R357A and V290M). Both the mutant forms of PPARG are deficient in eliciting a response to treatment with full and partial agonists. Our computational studies suggested that the molecule 3q performed better than the standard drug (Rosiglitazone) in all three protein structures. This implies that our suggested molecule could act as a more potent antagonist to native PPARG and could also be developed to treat type-2 diabetes patients with R357A and V290M mutations, which didn't elicit any response to currently available drugs in the market.


Assuntos
Cedrus/química , Cumarínicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Sulfonas/farmacologia , Cumarínicos/química , Relação Dose-Resposta a Droga , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Ligantes , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonas/química
7.
Nat Commun ; 12(1): 1871, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767189

RESUMO

Naturally-occurring membranes in the xylem tissue of gymnosperm sapwood enable its use as an abundantly-available material to construct filters, with potential to facilitate access to safe drinking water in resource-constrained settings. However, the material's behavior as a filter is poorly understood, and challenges such as short shelf life have not been addressed. Here, we characterize the operational attributes of xylem filters and show that the material exhibits a highly non-linear dependence of flow resistance on thickness upon drying, and a tendency for self-blocking. We develop guidelines for the design and fabrication of xylem filters, demonstrate gravity-operated filters with shelf life >2 years, and show that the filters can provide >3 log removal of E. coli, MS-2 phage, and rotavirus from synthetic test waters and coliform bacteria from contaminated spring, tap, and ground waters. Through interviews and workshops in India, we use a user-centric approach to design a prototype filtration device with daily- to weekly-replaceable xylem filters, and uncover indicators of social acceptance of xylem as a natural water filter. Our work enhances the understanding of xylem as a filtration material, and opens opportunities for engineering a diverse range of low-cost, biodegradable xylem-based filtration products on a global scale.


Assuntos
Cedrus/fisiologia , Filtração/métodos , Ginkgo biloba/fisiologia , Pinus/fisiologia , Purificação da Água/métodos , Bacteriófagos/isolamento & purificação , Água Potável/análise , Escherichia coli/isolamento & purificação , Filtração/instrumentação , Humanos , Rotavirus/isolamento & purificação , Purificação da Água/instrumentação , Xilema/fisiologia
8.
Environ Sci Pollut Res Int ; 28(27): 35880-35886, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33677673

RESUMO

Among the environmental pollution elements, one of the most important problems of the world today, air pollution and heavy metal pollution that have gradually increased after the industrial activities, are of significant importance. Heavy metals are not easily dissolved in nature. Moreover, they tend to bioaccumulate in living organisms, and some of them have a toxic or carcinogenic effect even at low concentrations. For this reason, it is crucial to monitor the heavy metal concentration in the air and monitor the changes. One of the efficient methods in observing the change of heavy metal concentrations in the air is the use of annual rings of trees as a biomonitor. The present study aimed to determine the annual change of Ni and Co concentrations, which are among the heavy metals related to traffic volume at most, in annual rings of Cedrus atlantica harvested in Kastamonu in late 2019. Within the scope of this study, the heavy metal concentrations in the inner and outer bark were compared to the heavy metal concentration in wood and the change of concentration in terms of direction was also analyzed. As a result of the present study, the highest concentrations in both heavy metals were found in the outer bark, whereas the transmission of metals within the wood was limited. It was found that Ni concentration significantly changed directionally in woods, and this change was related to the traffic volume. Thus, it was concluded that the annual rings of Cedrus atlantica were very suitable biomonitors to monitor Ni concentration change.


Assuntos
Poluição do Ar , Metais Pesados , Poluição do Ar/análise , Atmosfera , Cedrus , Monitoramento Ambiental , Metais Pesados/análise
9.
Food Chem ; 346: 128970, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422919

RESUMO

Cedarwood essential oil (CEO) has the effect of anti-inflammatory and anti-bacteria. However, the application of this essential oil is limited due to its strong volatility and poor water solubility. To address this issue, two types of oil-in-water CEO emulsions including CEO nanoemulsion (CEO-NE) and CEO Pickering emulsion (CEO-PE) were prepared. CEO-NE with 5% surfactant, had a smaller particle size (135.14 ± 1.1 nm) and higher absolute zeta potential value (32.75 mV) compared with CEO-PE (1% starch) which particle size was 626.21 ± 6.05 nm, zeta potential was 27.58 mV. The stability of CEO-NE and CEO-PE were tested by multiple light scattering, results showed that Turbiscan Stability Index (TSI) value of CEO-NE was much lower than that of CEO-PE. CEO-NE and CEO-PE exerted higher free radical scavenging activities, iron reducing power and antibacterial ability than CEO itself. These results indicated that emulsification is a feasible method to extend application of CEO.


Assuntos
Antibacterianos/química , Antioxidantes/química , Emulsões/química , Óleos Voláteis/química , Antibacterianos/farmacologia , Cedrus/metabolismo , Enterobacteriaceae/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Tamanho da Partícula , Reologia , Resistência ao Cisalhamento , Temperatura
10.
Mol Biol Rep ; 47(11): 8935-8947, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33150524

RESUMO

This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death.


Assuntos
Apoptose/efeitos dos fármacos , Cedrus/química , Ciclo Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Doença Aguda , Animais , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Células Jurkat , Células K562 , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Células RAW 264.7 , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Molecules ; 25(20)2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33050385

RESUMO

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cedrus/química , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Cromatografia Gasosa-Espectrometria de Massas , Células Hep G2 , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
J Nat Prod ; 83(10): 3021-3029, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32960603

RESUMO

Glioblastoma (GBM) is a common and aggressive brain tumor with a median survival of 12-15 months. Temozolomide (TMZ) is a first-line chemotherapeutic agent used in GBM therapy, but the occurrence of drug resistance limits its antitumor activity. The natural compound cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ and cedrol combination treatment resulted in consistently higher suppression of cell proliferation via regulation of the AKT and MAPK signaling pathways in GBM cells. The combination treatment induced cell cycle arrest, cell apoptosis, and DNA damage better than either drug alone. Furthermore, cedrol reduced the expression of proteins associated with drug resistance, including O6-methlyguanine-DNA-methyltransferase (MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated GBM cells. In the animal study, the combination treatment significantly suppressed tumor growth through the induction of cell apoptosis and decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage. These results imply that cedrol may be a potential novel agent for combination treatment with TMZ for GBM therapy that deserves further investigation.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Dano ao DNA , Metilases de Modificação do DNA/biossíntese , Enzimas Reparadoras do DNA/biossíntese , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Temozolomida/farmacologia , Proteínas Supressoras de Tumor/biossíntese , Animais , Antineoplásicos Alquilantes/toxicidade , Apoptose/efeitos dos fármacos , Cedrus/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Sinergismo Farmacológico , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Estrutura Molecular , Proteína Oncogênica v-akt/efeitos dos fármacos , Temozolomida/toxicidade , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Sci Rep ; 10(1): 14107, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839484

RESUMO

The use pesticide is one of the indispensable means to combat mosquito borne diseases. However, the repeated use of synthetic pesticides has induced resistance in the vector pest along with undesirable impact on the environment. The biodegradability, non-persistent and user's safety are the root cause to prefer plant-derived pesticides to synthetic ones. The botanical based pesticides tend to degrade rapidly under the influence of several environmental factors. For the feasible application as pesticides, the plant products are formulated either as liquid or as purely solid. Despite well-established formulation technology in pesticide delivery, their handling trouble is being ignored. There is difficulty in liquid formulation of pesticide products, as they are prone to splashing and spillage, resulting in contamination, wastage and direct exposure to skin; whereas a solid formulation tends to produce dust. In the present work, cedarwood (Cedrus deodara) essential oil embedded pectin nanocapsules were produced. The nanocapsules were characterized according to their morphology, size, encapsulation efficiency and thermal stability. Furthermore, the nanocapsules were impregnated onto mini cotton tea bags to be employed as RTU (ready to use) formulation for treating the breeding sites of mosquitoes. The larvicidal activity of the bags treated with pectin-cedar wood nanocapsules was assessed against malaria vector, Anopheles culicifacies and 98% mortality was recorded till 4 weeks, this suggests its potential and hassle free applications in controlling mosquito vector.


Assuntos
Anopheles/efeitos dos fármacos , Inseticidas/farmacologia , Malária/prevenção & controle , Mosquitos Vetores/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Agentes de Controle Biológico/farmacologia , Cedrus/química , Nanocápsulas , Pectinas , Chá/química
14.
Curr Top Med Chem ; 20(22): 1981-1992, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32703136

RESUMO

AIMS: The aim of this study is to explore essential oil from the bark of Cedrus deodara (CDEO) as an potential anticancer agent. BACKGROUND: The frontline drugs against cancer in clinical settings are posing challenges of resistance and other detrimental side-effects. This has led to the exploration of new anticancer chemical entities from natural sources, particularly plant-based products such as essential oils that serve as vast repositories of pharmacologically active substances for combating cancer. OBJECTIVE: The objective is to isolate and characterize the essential oil from the bark of Cedrus deodara (CDEO) and evaluate its potential as an anticancer agent and delineate the possible underlying mechanism of action. METHODS: Cedrus deodara essential oil from bark (CDEO) was obtained by hydro-distillation and analyzed by GC/MS for vital constituents. Further, in vitro cytotoxic potential was measured by MTT assay against a panel of cancer cell lines. The apoptosis-inducing potential of CDEO was analyzed by mitochondrial membrane potential loss (ΔΨm) and nuclear fragmentation assay. Besides, wound healing assay and colonogenic assay were employed to check the anti-metastatic potential of CDEO. Molecular docking approaches were employed for target identification, while immuno-blotting was carried out for target validation. RESULTS AND DISCUSSION: The major components identified were 2-(tert-Buyl)-6-methyl-3-(2- (trifluoromethyl) benzyl)imidazo [1,2-a]pyridine (26.32 %);9- Octadecenoic acid (8.015 %); Copaene (5.181 %);2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H- benzo[g]indazole(4.36 %) and 9(E),11(E)- Conjugated linoleic acid (4.299 %). Further, potent in vitro cytotoxic activity with IC50 values of 11.88 µg/ ml and 14.63 µg/ ml in colon cancer cell lines of HCT-116 and SW-620, respectively. Further, a significant and dose-dependent decrease in colony formation, cell migration, induction of ROS formation and loss in ΔΨm was observed. Additionally, major compounds identified were chosen for ligandprotein binding interaction studies to predict the molecular targets in colon cancer. It was observed that compounds such as 9-Octadecenoic acid;4H-1- Benzopyran-4-one, 3-(3,4-dimethoxyphenyl)-6,7- dimethoxy; 2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H-benzo [g]indazole and 2-Bornanol,5-(2,4- dinitro phenyl) hydrazono have a prominent binding affinity with NF-κB. This was also further validated by immuno-blotting results wherein CDEO treatment in colon cancer cells led to the abrogation of NFκB, and the Bcl-2-associated X protein (Bax): B-cell lymphoma (Bcl)-2 ratio was up-regulated leading to enhanced cleaved caspase 3 formation and subsequent apoptosis. CONCLUSION: These results unveil CDEO inhibits cell proliferation and induces apoptosis in colon cancer cells, which can be attributed to the abrogation of the NFκB signaling pathway.


Assuntos
Antineoplásicos/química , Cedrus/química , Neoplasias do Colo/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Óleos Voláteis/química , Casca de Planta/química , Extratos Vegetais/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ácido Linoleico/química , Simulação de Acoplamento Molecular , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos Vegetais/química , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Ácidos Esteáricos/química , Relação Estrutura-Atividade
15.
Ann Allergy Asthma Immunol ; 125(3): 311-318.e2, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32407947

RESUMO

BACKGROUND: Allergen immunotherapy can provide long-term benefits, including symptomatic relief and reduced disease progression, but it requires a lengthy regimen that presents barriers to patient adherence. Thus, there is a need for improved approaches to immunotherapy. Recently, several clinical trials have reported successful results from intralymphatic immunotherapy. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of intralymphatic immunotherapy for allergies caused by mountain cedar pollen in a proof-of-concept study. METHODS: A total of 21 patients with allergic rhinoconjunctivitis because of mountain cedar pollen were randomized to receive 3 monthly intralymphatic injections of allergenic extract or placebo before the 2018-2019 mountain cedar pollen season. Safety was monitored during treatment to the end of the pollen season using structured and spontaneous reports. Clinical efficacy information was collected using a daily electronic diary of symptoms and allergy medication. Allergen-specific serum immunoglobulin E was assessed before treatment and at the end of the study. RESULTS: There were no serious adverse events or systemic reactions in either group. A total of 4 patients experienced mild injection-site reactions. Patients receiving intralymphatic immunotherapy experienced a significant improvement in allergy symptoms and medication use relative to patients receiving placebo (P < .001), and the active treatment group had lower average total combined scores on 20 of 27 days during the peak pollen season (P < .05). There was no significant difference among groups in changes to mean mountain cedar-specific serum immunoglobulin E levels. CONCLUSION: In this proof-of-concept trial, intralymphatic immunotherapy was well tolerated and improved the symptoms and medication use associated with allergic rhinoconjunctivitis caused by mountain cedar pollen. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov under the registration number NCT03682965 before the enrollment of the first subject.


Assuntos
Cedrus/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Adulto , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Dessensibilização Imunológica/métodos , Método Duplo-Cego , Feminino , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/sangue , Injeções Intralinfáticas , Masculino , Pólen/imunologia
16.
J Ethnopharmacol ; 257: 112856, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278760

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb. ex D.Don) G. Don is applied as anti-inflammatory and anti-infection agents in folklore medicine. AIM OF THE STUDY: The present study aimed to assess the antimicrobial activity of Cedrus deodara (Roxb. ex D.Don) G. Don extract (CDE) against Streptococcus mutans biofilm formation and its biocompatibility, as well as to identify its chemical components. MATERIALS AND METHODS: Confocal laser scanning microscopy (CLSM), crystal violet staining, and CFU counting assay were applied to investigate the effect of CDE on S. mutans biofilm formation and extracellular polysaccharides (EPS) synthesis. The microstructure of S. mutans biofilms formed on glass coverslips and bovine enamel treated with CDE was observed by scanning electron microscopy (SEM). qRT-PCR was used to measure the expression of virulence genes gtfB, gtfC, and gtfD, and zymogram assay was performed to investigate the enzymatic activity of Gtfs. Moreover, HPLC-MS and NMR were applied to identify its chemical components. CCK-8 assay was also performed on human oral cells to evaluate its biocompatibility. RESULTS: Under the treatment of CDE, S. mutans formed less biofilm on both coverslips and enamel surfaces and synthesized less EPS. Moreover, CDE downregulated the expression of gtf genes and inhibited the enzymatic activity of Gtfs. According to HPLC-MS and NMR results, molecular structures of six main compounds in CDE were identified. CDE also has a good biocompatibility. CONCLUSIONS: CDE exhibits inhibitory activity against S. mutans and a good biocompatibility. It has the potential to be developed as anti-caries agents for clinical use.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cedrus , Cárie Dentária/prevenção & controle , Extratos Vegetais/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Biofilmes/crescimento & desenvolvimento , Cedrus/química , Cedrus/toxicidade , Células Cultivadas , Cárie Dentária/microbiologia , Regulação Bacteriana da Expressão Gênica , Glucosiltransferases/genética , Humanos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Streptococcus mutans/genética , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/patogenicidade , Virulência/genética , Fatores de Virulência/genética
17.
Pak J Pharm Sci ; 33(2): 695-703, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32276916

RESUMO

The DPPH radical scavenging potentials of the fractions were determined in comparison to positive controls such as quercetin with EC50 = 4.12±1.27, ascorbic acid with EC50 = 6.20±1.67, gallic acid with EC50 = 4.75±1.24 and α-tocopherol with EC50 = 32.50±1.57 µg/mL. The experiment showed that aqueous fractions of the bark extracts of Abies pindrow (fraction: C2) and Cedrus deodara (fraction: E2) showed significantly lower EC50 values of 2.5±0.5 and 2.5±0.6 µg/mL, respectively. In reducing power assay, lower EC50 values of 5.5 and 4.5µg/mL were recorded for the aqueous fraction (fraction: C 2) and final residue (fraction: C5), of Abies pindrow, respectively. The ethyl acetate, acetone and final fractions of knot wood of Picea smithiana were found significantly active against all bacterial strains. Of the most sensitive fractions towards all the fungal strains was ethyl acetate fraction obtained from the bark of Cedrus deodara with a zone of inhibition ranging from 75 to 88 % that was more than the standard fluconazole.


Assuntos
Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Casca de Planta , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Abies , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Cedrus , Avaliação Pré-Clínica de Medicamentos/métodos , Testes de Sensibilidade Microbiana/métodos , Pinaceae , Extratos Vegetais/farmacologia
18.
Bull Entomol Res ; 110(4): 535-541, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32148209

RESUMO

Better performance of generalist predators, as well as an increase in their density, may be an incentive factor in the ability of the predators to exploit more than one food item or mixed diets. In this study, the effects of four pollen grains (cedar, pear, apricot, and pistachio) when provided to Neoseiulus californicus in mixed diets with prey, Tetranychus urticae, were evaluated. The result indicated that the fastest female developmental time was observed on pistachio pollen + T. urticae, together with apricot pollen + T. urticae. Females reared on the mixed diet comprising pistachio pollen reflected the longest total life span duration, while the shortest total life span was observed in those on the diet that included pear pollen. Furthermore, the lowest fecundity, as well as the shortest reproduction period, was determined on the diets that included pear pollen, while the highest fecundity and the longest reproduction period were observed in pistachio pollen + T. urticae. In addition, the intrinsic (r) and finite rate of increase (λ), net (R0) and gross (GRR) reproductive rates were highest in pistachio pollen + T. urticae. These findings have important implications for developing a comprehensive biological control program of T. urticae, which will be discussed.


Assuntos
Dieta , Ácaros/fisiologia , Pólen , Animais , Cedrus , Fertilidade/fisiologia , Longevidade/fisiologia , Controle Biológico de Vetores , Pistacia , Comportamento Predatório , Prunus armeniaca , Pyrus , Tetranychidae
19.
Z Naturforsch C J Biosci ; 75(7-8): 255-264, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32092041

RESUMO

Gas chromatography-mass spectrometry analysis together with principal component analysis revealed that geographical origin influenced the yield and composition of the essential oils (EOs) extracted by hydrodistillation performed for 3 h using a Clevenger-type apparatus, from the cones of Cedrus libani A. Rich., growing wild at four Lebanese natural reserves and protected areas: Bsharri, Chouf, Ehden, and Tannourine, and from a cultivated cedar growing in Qartaba. Essential oil chemical variability established between the different studied provenances suggested the involvement of abiotic factors such as geographical conditions, cultivation conditions, soil composition, and environmental factors in the chemical polymorphism of C. libani cones EOs. α-Pinene/ß-pinene characterized Ehden (ß-pinene 35.6%/α-pinene 27.7%), Chouf (α-pinene 37.3%/ß-pinene 26.1%), Bsharri (α-pinene 27.7%/ß-pinene 21.4%), and Tannourine (α-pinene 25.1%/ß-pinene 16.0%) samples, whereas Qartaba EO was distinguished by the dominance of myrcene (30.6%), α-pinene(26%), and limonene (14.1%). Comparison with the existing literature reinforced the chemical variability of C. libani EOs. This current study helped the estimation of a best harvest location for a good EO quality production, resource optimization, and pharmacological properties evaluation, according to the market demand.


Assuntos
Cedrus/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Cedrus/química , Conservação dos Recursos Naturais , Destilação , Cromatografia Gasosa-Espectrometria de Massas , Líbano , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Análise de Componente Principal
20.
J Ethnopharmacol ; 253: 112545, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31918014

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus libani A. Rich (C. libani) is majestic evergreen Mediterranean conifer growing in the mountains of Lebanon. The ethnobotanical and traditional uses of cedar wood oil traces back to ancient times for the treatment of various ailments including cancer. Previous work in our laboratories revealed that himachalol (7-HC), a major sesquiterpene isolated from C. libani, possesses potent cytotoxic activity against various human cancer cell lines as well as promising anti-inflammatory effect in isolated rat monocytes. AIM OF THE STUDY: The present study aims to elucidate the mechanism of action behind the cytotoxic activity of 7-HC against murine melanoma cells (B16F-10) and evaluates its chemopreventive effect against chemically-induced skin carcinogenesis in mice. MATERIALS AND METHODS: 7-HC was extracted and purified from Cedrus libani wood. Cell viability was evaluated using WST-1 kit. Cell cycle analysis and apoptosis were assessed by Flow cytometry using propidium iodide (PI) and fluorescein Isothiocyanate (FITC)-conjugated Annexin V/PI staining respectively. Apoptosis related protein were quantified using western blot. The chemopreventive activity of 7-HC was evaluated for 20 weeks using a DMBA/TPA induced skin carcinogenesis model in Balb/c mice. RESULTS: 7-HC displayed a potent anti-proliferative activity against the melanoma cells with an IC50 of 8.8 µg/ml and 7.3 µg/ml at 24 and 48 h, respectively. Co-treatment with Cisplatin did not show any synergistic or additive effect on cell viability. Flow cytometry analysis using PI revealed that 7-HC treatment (5 and 10 µg/ml) induces the accumulation of cells in the sub-G1 phase and causes a decline in cell populations in the S and G2/M phases. Annexin/PI staining also reveals that 7-HC treatment significantly increases the percentage of cells undergoing early and late apoptosis. Western blot analysis shows that 7-HC treatment decreases the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic protein Bax. A reduction in the level of phosphorylated Erk and Akt was also observed. 7-HC via topical (2.5%), intraperitoneal (10, 25 and 50 mg/kg) or gavage (50 mg/kg) treatment revealed a significant decrease in papilloma volume with no adverse effect on liver and kidney function. CONCLUSIONS: The present study demonstrates that 7-HC treatment protects against chemically-induced skin carcinogenesis, promotes cell cycle arrest and induces apoptosis partially through an inhibition of both the MAPK/Erk and PI3K/Akt pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzocicloeptenos/farmacologia , Melanoma Experimental/tratamento farmacológico , Sesquiterpenos Policíclicos/farmacologia , Neoplasias Cutâneas/prevenção & controle , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Benzocicloeptenos/administração & dosagem , Benzocicloeptenos/isolamento & purificação , Cedrus/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinase/metabolismo , Sesquiterpenos Policíclicos/administração & dosagem , Sesquiterpenos Policíclicos/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Tempo
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