RESUMO
Silybum marianum, known as milk thistle (MT), is traditionally used to manage liver diseases. This study aimed to investigate the role of MT extract topical application as a potential treatment for imiquimod (IMQ)-induced psoriatic lesions in mice with particular emphasis on phosphoinositol-3 Kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and Kelch-like ECH-associated protein 1 (KEAP1)/ nuclear factor erythroid-2-related factor (NRF2)/ nuclear factor-kappa B (NF-κB) molecular cascades involvement. To address this aim, forty male Swiss albino mice were subdivided into four groups (n = 10 mice/group): control, IMQ model, standard group where mice were treated topically with IMQ, then the anti-psoriatic mometasone cream, and MT extract-treated group where mice were treated topically with IMQ followed by MT extract. In most measured parameters, MT extract, rich in silymarin, exhibited potent anti-psoriatic activity comparable to the standard cortisone treatment. MT extract mitigated dorsal skin erythema, scaling, and epidermal thickening, reflected by lowering the Psoriasis Area Severity Index (PASI) score. Moreover, it alleviated IMQ-induced splenomegaly. Mechanistically, the PI3K/AKT/mTOR pathway was the main functional pathway behind such improvements, where it was significantly inhibited by MT extract application. This led to NRF2 activation via KEAP1 downregulation with subsequent anti-inflammatory effect proven by reducing NF-κB, interleukin (IL)-23, and IL-17A and antioxidant ability proven by boosting the antioxidant glutathione and heme oxygenase-1. Such improvements were confirmed by alleviating the histopathological alteration. Thus, MT extract could be a promising therapeutic agent for psoriasis treatment by inhibiting PI3K/AKT/mTOR cascade, along with NRF2 signaling activation.
Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , NF-kappa B , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Extratos Vegetais , Proteínas Proto-Oncogênicas c-akt , Psoríase , Transdução de Sinais , Silybum marianum , Serina-Treonina Quinases TOR , Animais , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/induzido quimicamente , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Silybum marianum/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Humanos , Imiquimode , Modelos Animais de Doenças , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismoRESUMO
BACKGROUND: Pulmonary arterial hypertension, a common consequence of untreated CHD, is associated with a significant morbidity and mortality. Recent researches have demonstrated that patients with clinically severe cardiovascular illnesses, including pulmonary hypertension, have a greater mortality risk when their red cell distribution width is high. This work aimed to assess the predictive value of red cell distribution width in children with pulmonary arterial hypertension-CHD and to correlate red cell distribution width with various clinical and echocardiographic data. SUBJECTS AND METHODS: Sixty patients with CHD associated with pulmonary arterial hypertension were enrolled as the patient group. Another 60 patients with CHD and no pulmonary arterial hypertension, matched for age and sex, were enrolled as the control group. Electrocardiography and echocardiographic evaluation were performed for all included children. Red cell distribution width as part of the complete blood count was also performed using a Coulter® LH 700 series haematology analyzer. RESULTS: The red cell distribution width was significantly higher in the pulmonary arterial hypertension-CHD group than in the CHD-only group (P < 0.05). There was a significant positive correlation between the red cell distribution width and mean pulmonary artery pressure. Red cell distribution width was an independent predictor of mortality in children with pulmonary arterial hypertension-CHD. The best red cell distribution width cut-off for predicting mortality in children with pulmonary arterial hypertension-CHD was ≥ 17.6%. CONCLUSION: Red cell distribution width was significantly higher in children with pulmonary arterial hypertension-CHD than in those without pulmonary arterial hypertension. Moreover, red cell distribution width could be a cheap easy predictive marker for mortality in children with pulmonary arterial hypertension-CHD.
RESUMO
Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.
Assuntos
Azadirachta , Caspa , Rosmarinus , Caspa/tratamento farmacológico , Caspa/microbiologia , Alopecia/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Metabolomics study of Hydrocotyle umbellata L. revealed the richness of its aerial parts in phenolics primarily; quercetin and its glycoside derivatives, which are well-reported to exert antidiabetic activity owing to their powerful antioxidant capacity. Hence, the antioxidant and antidiabetic potentials of the quercetin standardized ethanolic extract of H. umbellata aerial parts were investigated. The antioxidant activity was examined by using in-vitro 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, while the antidiabetic activity was examined by using in-vitro α-glucosidase inhibitory assay and further confirmed by in-vivo experiments using streptozotocin-induced diabetes in rat model. Interestingly, the standardized ethanolic extract showed significant in-vitro antioxidant activity, and effectively inhibited Saccharomyces cerevisiae α-glucosidase enzyme activity. Moreover, it significantly reduced fasting blood glucose, triglycerides, and cholesterol levels. Thus, H. umbellata is a potential natural candidate to attenuate diabetes mellitus and its altered lipid profile complications, which could be attributed to its quercetin and quercetin glycosides content.
RESUMO
Eriobotrya japonica, commonly known as loquat, has been used traditionally for the treatment of different diseases. Herein, untargeted profiling based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to depict the phytochemical profile of loquat roots, leaves, stems, seeds, and fruits. This allowed the tentative annotation of 349 compounds, representing different phytochemical classes that included flavonoids, phenolic acids, lignans, stilbenes, and terpenoids. Among others, low molecular weight phenolics (tyrosol derivatives) and terpenoids were the most abundant phytochemicals. After that, in vitro antioxidant and enzyme inhibition assays were applied to investigate the biological activity of the different organs of Eriobotrya japonica. Roots of E. japonica exhibited the highest antioxidant capacity, showing 181.88, 275.48, 325.18, 169.74 mg Trolox equivalent (TE)/g in DPPH, ABTS, CUPRAC, and FRAP assays, respectively. Furthermore, the root extract of E. japonica strongly inhibited butyryl cholinesterase (3.64 mg galantamine equivalent (GALAE)/g), whereas leaves, stems, seeds, and fruits showed comparable inhibition of both acetyl and butyryl cholinesterases. All the investigated organs of E. japonica exhibited in vitro tyrosinase inhibition (57.27-71.61 mg Kojic Acid Equivalent (KAE)/g). Our findings suggest a potential food and pharmaceutical exploitation of different organs of E. japonica (mainly roots) in terms of enrichment with health-promoting phenolics and triterpenes.
Assuntos
Eriobotrya , Cromatografia Líquida de Alta Pressão , Metabolômica , Compostos Fitoquímicos , Extratos VegetaisRESUMO
Liver diseases are life-threatening and need urgent medical treatments. Conventional treatment is expensive and toxic, so the urge for nutraceutical hepatoprotective agents is crucial. This study is considered the first metabolic profile of Aeschynomene elaphroxylon (Guill. & Perr.) extracts of; flowers, leaves & bark adopting UPLC-Orbitrap HRMS analysis to determine their bioactive metabolites, and it was designed to investigate the potential hepatoprotective activity of A. elaphroxylon flowers and bark extracts against CCl4-induced hepatic fibrosis in rats. Forty-nine compounds of various classes were detected in the three extracts, with triterpenoid saponins as the major detected metabolite. Flowers and bark extracts presented similar chemical profile while leaves extract was quite different. The antioxidant activities of the flowers, leaves & bark extracts were measured by in vitro assays as Fe+3 reducing antioxidant power and Oxygen radical absorbance capacity. It revealed that flowers and bark extracts had relatively high antioxidant activity as compared to leaves extract. Based on the metabolic profile and in vitro antioxidant activity, flowers and bark ethanolic extracts were chosen for alleviation of hepatotoxicity induced by CCl4 in rats. The hepatoprotective activity was studied through measuring hepatotoxicity biomarkers in serum (ALT, AST, and Albumin). Liver tissues were examined histopathologically and their homogenates were used in determining the intracellular levels of oxidative stress biomarkers (MDA, GSH), inflammatory markers (TNF-α). Flowers and bark ethanolic extracts exerted a significant hepatoprotective effect through reduction in the activities of ALT, AST and Albumin, the tested extracts reduced oxidative stress by increasing GSH content and reducing the MDA level. Furthermore, the extracts decreased levels of pro-inflammatory TNF-α. Moreover, the present study revealed the potentiality of A. elaphroxylon in ameliorating the CCl4-induced hepatic fibrosis in rats. In this aspect, A. elaphroxylon can be used with other agents as a complementary drug.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fabaceae/química , Fígado/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fabaceae/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Metaboloma , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/metabolismo , Substâncias Protetoras/metabolismo , Ratos WistarRESUMO
OBJECTIVE: Acute B lymphoblastic leukaemia (B-ALL) is the most common type of childhood malignancy worldwide but little is known of its origin. Recently, many studies showed both a high incidence of Epstein-Barr virus (EBV) infection and high levels of CD4+CD25+Foxp3+(Treg cells) in children with B-ALL. In our study, we investigated the possible relationship between EBV infection and the onset of B-ALL, and its relation to expression of CD4+, CD25high+Foxp3+ T regulatory cells. SUBJECT AND METHODS: We analysed expression and mean fluorescence intensity (MFI) of Treg cells in peripheral blood of 45 children with B-ALL and in 40 apparently healthy children as a control, using flow cytometry. Serum anti-EBV viral capsid antigen (VCA) IgG, anti-EBV nuclear antigen (EBNA) IgG (for latent infection) and anti-EBV VCA IgM (for acute infection) were investigated using ELISA. RESULTS: Analysis of the Treg cells population in patients and controls revealed that expression of CD4+ CD25high+ T lymphocytes was higher in patients than in controls (mean±SD 15.7±4.1 and 10.61±2.6 in patients and controls, respectively, and MFI of Foxp3 was 30.1±7.1 and 16.7±3.7 in patients and controls, respectively (p<0.001)). There was a high incidence of latent EBV infection in patients (31%) compared with controls (10%) while the incidence of acute infection was 12% in patients and 0% in the control group. To study the role of latent EBV infection in the pathogenesis of acute B-ALL, OR was calculated (OR=4.06, coefficient index 1.2-13.6). CONCLUSIONS: These findings suggest a possible role for Treg cells and EBV in the pathogenesis of B-ALL. Further studies are needed on the possible mechanisms of tumour genesis related to Treg cells and EBV in children with B-ALL.
Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Linfócitos T Reguladores/imunologia , Criança , Pré-Escolar , Egito , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Linfócitos T Reguladores/patologia , Linfócitos T Reguladores/virologiaRESUMO
We aimed to explore the expression of CD34 and its impact on the disease outcome in patients with APL. The study comprised 40 de novo APL patients. Diagnostic tools included peripheral blood and bone marrow morphology and cytochemistry, immunophenotyping, cytogenetic studies, and PML/RARα fusion gene detection using RT-PCR. CD34 was expressed in 13 (32.5%) of cases with higher expression in M3v compared to M3 subtype. All M3v cases were CD34+, while only 7.4% of M3 cases were CD34+. CD34+ cases were associated with significant higher white blood cell count and peripheral blood promyelocytes. No significant association was found between PML/RAR-α isoform and molecular remission. CD34+ expression was significantly associated with decreased incidence of molecular remission and increased incidence of early death. The overall survival of patients with WBC count >11 × 103/µl was inferior to patients with WBC count <11 × 103/µl, but no significant differences were observed in overall survival between CD34- and CD34+ or between bcr1 and bcr3 groups. Immunophenotypic analysis for CD34 could distinguish an APL subset with different biological characteristics and adverse prognostic outcome.
Assuntos
Antígenos CD34/metabolismo , Leucemia Promielocítica Aguda/classificação , Leucemia Promielocítica Aguda/metabolismo , Adolescente , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/terapia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Isoformas de Proteínas , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
The purpose of this study was to investigate the impact of oil pollution in a desert location (the Greater Al-Burgan oil fields, an area damaged in the Gulf War in 1991) in Kuwait on the hepatotoxicity of the Sand lizard Acanthodactylus scutellatus (A. scutellatus). Twenty lizards (10 of each sex) from each polluted and each control sites were collected. Livers were removed from dissected animals and ready for fixation by Bouin's solution and formal-saline. Twenty sections (10 from males and 10 from females) from each tar mat (polluted) and control sites were prepared and examined for cell diameter and nuclear measurements using Cell Analysis Systems. The cytology of hepatocytes showed normal appearance in samples from the control sites. Dead cells were abundant in the sections of lizard livers from the tar mat sites and occurred in notably greater numbers than the sections of livers of animals from the control sites. Examinations of the data confirm that the cell and nuclear diameters in liver samples of males collected from polluted sites were generally greater than those of corresponding females. The liver sections obtained from animals in the tar mat site had greater cellular diameters than counterparts from control sites. Females from the polluted sites were also affected by oil pollution by having larger hepatocyte diameters and their nuclei were also affected, being larger than female nuclei from the control sites. The most remarkable feature observed in hepatocytes of lizards collected from the tar mat sites were swelling of hepatocytes, ballooning degeneration of hepatic cytoplasm and cell death. This study confirmed that the prolonged exposure to oil pollution may result in increased accumulation of contaminants and may cause severe liver pathology in a range of wild organisms such as A. scutellatus.
Assuntos
Fígado/efeitos dos fármacos , Lagartos/fisiologia , Petróleo/toxicidade , Poluentes do Solo/toxicidade , Animais , Monitoramento Ambiental , Poluição Ambiental/estatística & dados numéricos , Feminino , Kuweit , Fígado/patologia , Masculino , Petróleo/análise , Poluentes do Solo/análiseRESUMO
Using indicator species to monitor the effects of oil pollution was thought to be useful to assess whether local desert reptiles and their insect prey could fulfill such a role in an area damaged in the second Gulf War (1990). Polluted sites with apparently different degrees of contamination (namely tar mat, soot, and clear sites) located at Kuwait's Greater Al-Burgan oil field were compared with control areas outside this region in study conducted in 2002. Five Acanthodactylus scutellatus lizards from each study and control site were humanely killed and stored in a freezer at -20 degrees C until analysis. Ants from the same sites were also collected and treated in a similar manner. Lizard and ant whole body tissues were subjected to gas chromatography-mass spectrometry (GC-MS) to determine concentrations of petroleum hydrocarbons (HCs). The study concentrated on sixteen polycyclic aromatic hydrocarbons (PAHs), EPA priority pollutants used as indicators of petrogenic HC contamination. There were significantly different concentrations of total PAHs in lizards and ants among all four study sites. Of the 16 PAHs, phenanthrene, fluoranthene, and benzo[a]anthracene were present in both lizard and ant samples from the Greater Al-Burgan oil field sites irrespective of the apparent degree of pollution but were undetectable in materials from the control sites. The range of total PAHs in lizards was 26.5-301 ng g(-1) and it was 6.7-82.1 ng g(-1) in ants. Concentrations increased progressively along an expected contamination gradient. Total PAHs were detected in biota even in an area (clear site) that did not appear, virtually, to contain petroleum soil pollution which supports the value of indicator biota species. For all three sites where PAHs were found in biota, the ratio of total PAHs in ants to lizards was consistently 3.3-3.4. These data show that, although 12 years have passed since the Kuwait oil spill catastrophe, all sites are still contaminated with PAHs. Use of lizard and ant materials in monitoring such desert locations seems to be an effective strategy.