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1.
Mar Drugs ; 22(2)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38393056

RESUMO

In this study, we investigated for the first time the anti-inflammatory and immunomodulatory properties of crude polysaccharide (PSHT) extracted from green marine algae Halimeda tuna. PSHT exhibited anti-oxidant activity in vitro through scavenging 1, 1-diphenyl-2-picryl hydroxyl free radical, reducing Fe3+/ferricyanide complex, and inhibiting nitric oxide. PSHT maintained the erythrocyte membrane integrity and prevented hemolysis. Our results also showed that PSHT exerted a significant anti-edematic effect in vivo by decreasing advanced oxidation protein products and malondialdehyde levels and increasing the superoxide dismutase and glutathione peroxidase activities in rat's paw model and erythrocytes. Interestingly, PSHT increased the viability of murine RAW264.7 macrophages and exerted an anti-inflammatory effect on lipopolysaccharide-stimulated cells by decreasing pro-inflammatory molecule levels, including nitric oxide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α). Our findings indicate that PSHT could be used as a potential immunomodulatory, anti-inflammatory, anti-hemolytic, and anti-oxidant agent. These results could be explained by the computational findings showing that polysaccharide building blocks bound both cyclooxygenase-2 (COX-2) and TNF-α with acceptable affinities.


Assuntos
Clorófitas , Alga Marinha , Ratos , Camundongos , Animais , Antioxidantes/farmacologia , Óxido Nítrico/metabolismo , Alga Marinha/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular , Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Lipopolissacarídeos/farmacologia , Clorófitas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo
2.
Toxicol Mech Methods ; 34(5): 495-506, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38166540

RESUMO

The current study aimed to assess the antioxidant and antiproliferative effects of teucrium polium extract: computational and in vivo study in rats. Three groups of animals: Group (i) constitute the control group; Group (ii) HeLa group received an intrafemoral inoculation of HeLa cells and Group (iii) constitue the combination between HeLa + T. polium. The plant was administered by gavage. Our results revealed that HeLa cell injection showed an elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), creatinine, urea, calcium and phosphorus. The pretreatment with the plant extract reduced the level of these parameters. Injection of HeLa cells showed a significant decrease in phosphorus and calcium respectively. However, the pretreatment by T. polium modulated the level of these two minerals. Rats treated with HeLa cells line showed an increase in the level of lipid peroxidation as evaluated by the TBARS substances, at the same time, a significant decreases in SOD, CAT and GPx activities were noted in the HeLa group compared to the control. On the other hand, pretreatment with the plant improved the level of these enzymes. Our results revealed that T.polium has a therapeutic effect on some health problems. HeLa cell line induced a small infiltration in liver and kidney. T. polium reduced the damage in both liver and kidney, but did not reveal any proliferation of tumor cells from trabecular bone tissue. The computational study revealed that T. polium compound bound with high free binding energies and established promising network of molecular interactions with COX-2 and TNF-α macromolecules.


Assuntos
Antioxidantes , Proliferação de Células , Extratos Vegetais , Teucrium , Animais , Teucrium/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Células HeLa , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Masculino , Ratos Wistar , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Simulação de Acoplamento Molecular
3.
Molecules ; 28(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37959858

RESUMO

Plants with medicinal benefits are a crucial source of compounds for developing drugs. This study was designed to determine the chemical composition, antibacterial, antibiofilm, antioxidant, and anti-enzymatic activities of Pulicaria incisa (Lam.) DC. We also reported the molecular interaction between identified molecules and several receptors associated with antimicrobial and antibiofilm activities. A total of seventeen and thirteen compounds were identified in aqueous and methanolic extracts of P. incisa, respectively. The methanolic extract yielded a higher total content of polyphenols and flavonoids of about 84.80 ± 2.8 mg GAE/g and 28.30 ± 1.2 mg QE/g, respectively. Significant antibacterial activity was recorded for both extracts, with minimum inhibitory concentration (MIC) values ranging from 30 to 36 µg/mL, and the result was comparable to the reference antibiotic control. Antibiofilm assays revealed that both extracts were able to reduce the attachment of bacterial cells to 96-well plates, but the highest antibiofilm activity was recorded against Staphylococcus aureus. The methanolic extract also showed anti-enzymatic potency and high antioxidant activity, as demonstrated by all assays used, including DPPH, FRAP, and ABTS. These results were further validated by in silico approaches, particularly the molecular interaction of the identified compounds with the targeted receptors. These findings present P. incisa as a significant source of antibacterial, antibiofilm, antioxidant, and anti-enzymatic molecules.


Assuntos
Antioxidantes , Pulicaria , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Metanol
4.
Calcif Tissue Int ; 110(4): 475-488, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34988595

RESUMO

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion, BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.


Assuntos
Neoplasias da Mama , Osteólise , alfa-Tocoferol , Animais , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Ciclo-Oxigenase 2 , Suplementos Nutricionais , Osteólise/tratamento farmacológico , Osteólise/patologia , Ratos , Fator de Necrose Tumoral alfa , Microtomografia por Raio-X , alfa-Tocoferol/farmacologia
5.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 42-55, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809303

RESUMO

In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was designed to explore the nephroprotective efficacy of polyherbal (PH) extract in a diabetic model induced by streptozotocin (STZ). STZ (55 mg/kg body weight, intraperitoneal) was injected in overnight fasting rats to develop the diabetic experimental model. Effect on kidney injury was evaluated by investigating biochemical and histological evidences in renal tissue after 56 days of treatment of PH extract. Results showed the high glucose level in STZ treated rats that suggested hyperglycemia persistence along with the successful establishment of nephropathy in diabetic rats with altered renal function, inflammatory cytokines level as well as oxidative and nitrosative stress. Administration of PH extract significantly improved the glycemic condition, glomerular function and proximal reabsorptive markers. Further, elevated pro-inflammatory cytokines levels and disturbed redox status were restored. Moreover, findings were fostered and substantiated by histopathological examinations. Our work strongly proposes that the nephroprotective effect of the PH extract on renal damage could be attributed due to its anti-inflammatory and antioxidant properties. Thus, PH extract could have potential as a pharmaceutical drug for diabetes mellitus (DM). Additional long-term study or clinical trial is required for further investigations.


Assuntos
Diabetes Mellitus Experimental , Insuficiência Renal , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Rim/metabolismo , Modelos Teóricos , Estresse Oxidativo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Insuficiência Renal/complicações , Estreptozocina/farmacologia
7.
Molecules ; 26(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525415

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10-3 to 5.47 × 10-6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.


Assuntos
Enzima de Conversão de Angiotensina 2 , Cloroquina/química , Hidroxicloroquina/química , Simulação de Acoplamento Molecular , Polimorfismo Genético , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Cloroquina/farmacocinética , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapêutico , Domínios Proteicos , SARS-CoV-2/química , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Tratamento Farmacológico da COVID-19
8.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443463

RESUMO

In our study, Allium subhirsutum L. (AS) was investigated to assess its phenolic profile and bioactive molecules including flavonoids and organosulfur compounds. The antioxidant potential of AS and wound healing activity were addressed using skin wound healing and oxidative stress and inflammation marker estimation in rat models. Phytochemical and antiradical activities of AS extract (ASE) and oil (ASO) were studied. The rats were randomly assigned to four groups: group I served as a control and was treated with simple ointment base, group II was treated with ASE ointment, group III was treated with ASO ointment and group IV (reference group; Ref) was treated with a reference drug "Cytolcentella® cream". Phytochemical screening showed that total phenols (215 ± 3.5 mg GAE/g) and flavonoids (172.4 ± 3.1 mg QE/g) were higher in the ASO than the ASE group. The results of the antioxidant properties showed that ASO exhibited the highest DPPH free radical scavenging potential (IC50 = 0.136 ± 0.07 mg/mL), FRAP test (IC50 = 0.013 ± 0.006 mg/mL), ABTS test (IC50 = 0.52 ± 0.03 mg/mL) and total antioxidant capacity (IC50 = 0.34 ± 0.06 mg/mL). In the wound healing study, topical application of ASO performed the fastest wound-repairing process estimated by a chromatic study, percentage wound closure, fibrinogen level and oxidative damage status, as compared to ASE, the Cytolcentella reference drug and the untreated rats. The use of AS extract and oil were also associated with the attenuation of oxidative stress damage in the wound-healing treated rats. Overall, the results provided that AS, particularly ASO, has a potential medicinal value to act as effective skin wound healing agent.


Assuntos
Allium/química , Antioxidantes/farmacologia , Dermatite/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Tecido de Granulação/efeitos dos fármacos , Masculino , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , Ratos Wistar
9.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208908

RESUMO

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.


Assuntos
Inibidores Enzimáticos/química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Naftoquinonas/química , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Regulação Alostérica , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Relação Estrutura-Atividade
10.
Medicina (Kaunas) ; 57(10)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34684095

RESUMO

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.


Assuntos
Preparações Farmacêuticas , Neoplasias da Bexiga Urinária , Animais , Reposicionamento de Medicamentos , Humanos , Ivermectina/farmacologia , Simulação de Acoplamento Molecular , Schistosoma haematobium , Neoplasias da Bexiga Urinária/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
11.
Pestic Biochem Physiol ; 167: 104606, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527427

RESUMO

We have investigated the effect of subchronic exposure to tetradifon (TDF), as an endocrine disruptor chemical, on some parameters related to serious metabolomic disorders such as obesity, type 2 diabetes and hyperlipidemia. TDF promoted significant increases in both duodenal and pancreatic α-amylase and lipase especially in the 12-weeks treated rats. Plasmatic glucose and lipid profile; total cholesterol (T-cholesterol), low density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c) and glyceride, were markedly disrupted. Compared with controls, biochemical liver injury parameters: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and lactate dehydrogenase (LDH) were significantly increased. Moreover, notable pathological features were reported in liver tissues. These results confirm a strong relationship between exposure to an endocrine disruptor and metabolic disorders. In fact, subchronic exposure to TDF lead to lipidemic and glycemic disruption associated hyperactivity in both α-amylase and lipase. Overall, these disruptions could be an important step on the pathway to metabolic pathology.


Assuntos
Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Animais , Hidrocarbonetos Clorados , Lipase , Fígado , Ratos , alfa-Amilases
12.
Toxicol Mech Methods ; 29(5): 313-321, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30676168

RESUMO

This work investigated the protective effects of Teucrium polium (T. polium) and vitamin C (Vit C) against carbon tetrachloride (CCl4) induced hepatotoxicity and nephrotoxicity in rats. T. polium reduced the Fer reduced antioxidant power (FRAP) (IC50 = 0.89 mg/ml) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 0.049 µg/ml) than Vit C, FRAP (IC50 = 0.71 mg/ml) and DPPH (IC50 = 0.029 µg/ml). Male albino Wistar rats were divided into six groups: Group I was used as controls, Group II received CCl4 in olive oil (0.5 ml/kg) by gavage, Group III received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving T. polium (5 g/l), orally, Group IV received T. polium (5 g/l) alone, by gavage, for 7 d, Group V received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving Vit C (250 mg/kg) by gavage and Group VI received Vit C (250 mg/kg) alone by gavage. CCl4 showed an increase of serum hepatic and renal markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. Moreover, we noted an increase of lipid peroxidations and a decrease in antioxidants enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) of CCl4 rats compared to controls. The pretreatment with (200 mg/kg) of T. polium and with Vit C (250 mg/kg) by gavage, for 7 d, displayed their ability to protect against oxidative damage and biochemical changes induced by CCl4. Our results were in accordance with histopathological observations.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Tetracloreto de Carbono/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Teucrium/química , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Rim/enzimologia , Rim/patologia , Fígado/enzimologia , Fígado/patologia , Extratos Vegetais/metabolismo , Ratos Wistar
13.
Ecotoxicol Environ Saf ; 129: 164-70, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27039245

RESUMO

Air pollution is a threat for human health and wildlife. The aim of this study is to assess the pathophysiological changes and the oxidative-antioxidative status in testicular tissues of 40 Hybrid sparrows collected from four areas in Gabès city, one of the most polluted areas in Tunisia. The testis histopathological analysis revealed alterations in birds from Ghannouche, the polluted area. The thiobarbituric acid reactive substance (TBARS) levels were higher in testis of birds from the contaminated site compared to less polluted areas indicating oxidative damage to membrane lipids. Antioxidant enzyme activities (superoxide dismutase and catalase) were lower in testis sparrows from the polluted site compared with the reference site, suggesting deficiency of the antioxidant system to compensate for oxidative stress. Overall, our results suggest that the hybrid sparrow offers a suitable model for biomonitoring programs of atmosphere pollutants and the selected biomarkers could be useful tool to evaluate pollution impacts in living organisms.


Assuntos
Poluição Ambiental , Pardais/fisiologia , Testículo/metabolismo , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Cidades , Monitoramento Ambiental/métodos , Poluição Ambiental/efeitos adversos , Masculino , Estresse Oxidativo/fisiologia , Reprodução , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tunísia
14.
Tumour Biol ; 35(4): 3663-70, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24318993

RESUMO

This study was designed to assess femur angioarchitecture and hematological effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor osteolysis was induced by in situ inoculation of Walker 256/B malignant cells. Six other rats were sham operated and served as control. Twenty days later, rats were euthanized, and femurs were collected than radiographed. Angioarchitecture [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2 different positions (P1: diaphysis, and P2: metaphysis) of the operated femora. Some hematological parameters were also assessed. Walker 256/B induced marked tumor osteolysis, with cortical perforation and trabecular destruction, associated increase in bone vascularization (increases of VNb and VV and decrease of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD and lower WTh. These effects were more prominent in P2. When compared to Sham group, significantly decreases at levels of red blood cell (RBC), hemoglobin (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats. These results suggest that Walker 256/B cells induced tumor osteolysis, improve hypervasculature especially near the tumoral foci (P2) associated hematological disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and disorganized morphology.


Assuntos
Carcinoma 256 de Walker/irrigação sanguínea , Fêmur/irrigação sanguínea , Osteólise/etiologia , Animais , Carcinoma 256 de Walker/sangue , Carcinoma 256 de Walker/diagnóstico por imagem , Carcinoma 256 de Walker/patologia , Modelos Animais de Doenças , Feminino , Fêmur/patologia , Hemoglobinas/análise , Humanos , Masculino , Radiografia , Ratos , Ratos Sprague-Dawley
15.
Artigo em Inglês | MEDLINE | ID: mdl-38982700

RESUMO

BACKGROUND: The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial. METHODS: Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study. RESULTS: Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control. CONCLUSION: The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.

16.
J Biomol Struct Dyn ; 42(3): 1368-1380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37191027

RESUMO

A revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitro and computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli (Clinical strain, 217), S. aureus followed by E. coli ATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma.


Assuntos
Anti-Infecciosos , Mel , Ziziphus , Antibacterianos/farmacologia , Staphylococcus aureus , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas , Escherichia coli , Simulação de Acoplamento Molecular , Bactérias Gram-Positivas , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química
17.
Pharmaceuticals (Basel) ; 17(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38931340

RESUMO

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

18.
ACS Omega ; 9(24): 26724-26734, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911808

RESUMO

The cactus family plant has been used in folk medicine for a long time. In this work, Opuntia stricta chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that O. stricta is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 µg/g), apigenin-7-Glu (3.15 µg/g), and catechin (2.85 µg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. In vivo, the methanol extract from Opuntia stricta showed anti-inflammatory activity. The computational modeling reveals that O. stricta compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both in vitro and in vivo findings. These data indicate that Opuntia stricta cladode powder could be potentially useful in pharmaceutical and food applications.

19.
Mar Pollut Bull ; 205: 116668, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38972217

RESUMO

Two concentrations (6.25 and 1.25 mg/L) were used for two Parkinson's disease medications, Benserazide, and Trihexyphenidyl, to test their effects on the meiobenthic nematofauna. It is predicted that these highly hydrosoluble drugs will end up in marine environments. The results showed that both medications when added alone, induced (i) important changes in the numbers and (ii) taxonomic composition. The impact of Benserazide and Trihexyphenidyl was also reflected in the (iii) functional traits of nematofauna, with the most affected categories following exposure being the trophic group 1B, the clavate tails, the circular amphids, the c-p2 life history, and the body length of 1-2 mm. These results were supported by the molecular interactions of the studied drugs with both GLD-3 and SDP proteins of Caenorhabditis elegans. (iv) The mixtures of both drugs did not show any changes in the nematode communities, suggesting that no synergistic or antagonistic interactions exist between them.


Assuntos
Antiparkinsonianos , Benserazida , Caenorhabditis elegans , Triexifenidil , Animais , Antiparkinsonianos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Poluentes Químicos da Água , Nematoides/efeitos dos fármacos
20.
Life (Basel) ; 13(7)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37511909

RESUMO

The present study aimed to molecularly identify and characterize the hard ticks infesting camels from the northern region (Ha'il province) of Saudi Arabia using the mitochondrial barcoding gene cytochrome oxidase subunit I (COI). The sequences of tick samples from camels in three regions of Ha'il were aligned with those previously reported from different geographic regions, revealing nine haplotypes, of which six were newly described in this study for the first time. These haplotypes were used to determine their phylogenetic relationships using the maximum likelihood method, displaying two distinct clades corresponding to Hyalomma dromedarii and H. impeltatum. Moreover, the haplotypes showing the highest homology with those deposited in NCBI-GenBank from different geographic regions, including Saudi Arabia, were obtained and combined to determine their phylogenetic relationships among them. The results showed that the haplotypes belonging to two clades were grouped with those previously determined as H. dromedarii and H. impeltatum. Moreover, the presence of H. scupense (syn. H. detritum) together with H. impeltatum suggests possible asymmetrical hybridization and mitochondrial introgression between these species. H. scupense infesting different mammal species apart from camels were also clustered in a different clade, indicating the presence of different lineages of this species that show different host specificities.

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