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Cancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressure in tumors. To tackle these challenges, targeted therapy, specifically targeting HER2 (Human Epidermal Growth Factor Receptor 2) as well as EGFR (Epidermal Growth Factor Receptor), is considered a promising approach in cancer treatment. In recent years, phytocompounds have gained recognition as a potential source of chemopreventive and chemotherapeutic agents in tumor cancer treatment. Phytocompounds are compounds derived from medicinal plants that have the potential to treat and prevent cancer. This study aimed to investigate phytocompounds from Prunus amygdalus var amara seeds as inhibitors against EGFR and HER2 enzymes using in silico methods. In this study, fourteen phytocompounds were isolated from Prunus amygdalus var amara seeds and subjected to molecular docking studies to determine their ability to bind to EGFR and HER2 enzymes. The results showed that diosgenin and monohydroxy spirostanol exhibited binding energies comparable to those of the reference drugs, tak-285, and lapatinib. Furthermore, the drug-likeness and ADMET predictions, performed using the admetSAR 2.0 web-server tool, suggested that diosgenin and monohydroxy spirostanol have similar safety and ADMET properties as the reference drugs. To get deeper insight into the structural steadiness and flexibility of the complexes formed between these compounds and theEGFR and HER2 proteins, molecular dynamics simulations were performed for 100 ns. The results showed that the hit phytocompounds did not significantly affect the stability of the EGFR and HER2 proteins and were able to form stable interactions with the catalytic binding sites of the proteins. Additionally, the MM-PBSA analysis revealed that the binding free energy estimates for diosgenin and monohydroxy spirostanol is comparable to the reference drug, lapatinib. This study provides evidence that diosgenin and monohydroxy spirostanol may have the potential to act as dual suppressors of EGFR and HER2. Additional in vivo and in vitro research are needed to certify these results and assess their efficacy and safety as cancer therapy agents. The experimental data reported and these results are in agreement.
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Background: Crataegus aronia (C. aronia) extracts have been used medicinally since ancient times and are often utilized in traditional Arab medicine. An extensive study has revealed that Crataegus species have antioxidant, antibacterial, anti-inflammatory, and hypotensive properties. Objectives: This work was performed to explore the phytochemical contents of C. aronia extract, as well as its antioxidant and antibacterial properties, and to assess the lipid peroxidation level as an oxidative stress biomarker in erythrocytes. Methods: Chemical constituents in the methanolic extract of C. aronia were identified by gas chromatography-mass spectrometry and their relative concentrations were determined. The antioxidant activity of C. aronia extract was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The effect of C. aronia on the concentration of malondialdehyde (MDA) in the erythrocyte hemolysates was studied. Also, the crude extract was assessed for its antimicrobial activity through agar diffusion and microbroth dilution assays. Key findings: The DPPH IC50 value of the extract showed that the antioxidants activity was equal to (14.3 µg/mL) and according to FRAP assay, the antioxidant activity was in the range of 33.9 µmol-82.86 µmol Fe+2/g dw. The extract exerts a protective effect against oxidative stress in RBCs and shows a 50% inhibition of malonyldialdehyde (MDA) at 39.48 µg/mL extract. Minimum inhibitory concentrations were found in the range of 800-1000 µg/mL of leave extracts. The phytochemical analysis showed that the total phenols, flavonoids, and flavonols content were 494.071 mg GAE/g extract, 155.251 mg RE/g extract, and 103.2049 mg RE/g extract). C. aronia extract contains alkaloids, flavonoids, terpenoids, and steroids. Crude extract of C. aronia was more potent in inhibiting the growth of B. subtilis, S. aureus and M. luteus with MIC and MBC values of 800,800 and 1000 µg/mL, respectively. According to GC-MS, 20 compounds were identified: dihydro-3-methylene-5-methyl-2-furanone (14.71%), hexanoic acid (6.57%), ethyl 3,5-ditert-butyl-4-hydroxybenzoate (6.4%), N, N-dimethylheptadecan-1-amine (4.91%), methyl 2-oxobutanoate (4.14%), glyceraldehyde (3.98%), and 2-methoxy-1-(2-nitroethenyl)-3-phenylmethoxybenzene (3.16%), were the major constituents. Conclusion: This study may open a window of hope for children with Glucose-6-phosphate dehydrogenase disorder by possible utilization of the active ingredients of C. aronia to minimize both oxidative stress and infection which negatively impact the disease sequelae.According to these in vitro experiments, this plant extract has a significant amount of natural antioxidants, which may aid in the protection of various oxidative stresses. As a result, employing the active components of C. aronia to minimize oxidative stress and infection, both of which have a detrimental impact on disease sequelae, may bring hope to children with Glucose-6-phosphate dehydrogenase disorder.
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The most efficient and safe source of medications is the natural and traditional medications which are produced from plants and herbs. In this study, Sisymbrium officinale (S. officinale) was tested to explore its total phenolic and flavonoids contents. Antioxidant, antimicrobial, and anticancer activities were assessed as well. S. officinale was bought from a local Palestinian market, air-dried, and extracted with 99% ethanol with the aid of ultrasonication. The extract was tested on three types of bacteria using well diffusion method. The anti-microbial testing included three different types of bacteria, two gram-positive bacteria, Streptococcus and Staphylococcus and E. coli as a gram-negative bacterium. Antioxidant activity of the plant extract was conducted using DPPH method, while total phenolic and flavonoids contents were performed using a well-known assay chemical method. Anticancer activity of the extract was conducted against two cancer cell lines (breast (MCF7) and colon (HCT116) cancer cell lines). Results showed that the extract is rich polyphenolic and flavonoids and has strong antioxidant activity reflected by inhibition of free radicals (DPPH) (193.7 ± 3.4). The plant extract showed also strong antimicrobial activity against both E. coli and Streptococcus bacteria with of inhibition of 10 and 14 mm respectively. The extract of this plant also showed anticancer activity (about 6%) against MCF7 (breast cancer cell line).
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Ghrelin is a peptide hormone with direct or indirect effects on obesity and asthma. More data are required to understand the effect of ghrelin on the control and pathogenesis of these diseases. The aim of this study was to evaluate ghrelin levels in selected groups of children to identify the association between serum ghrelin, obesity, and the severity of asthma. The study included 401 school children selected from the Najran area and grouped into non-obese asthmatics, obese asthmatics, obese non-asthmatics and controls (non-obese non-asthmatics). Blood levels of ghrelin, interleukin (IL)-4, IL-5 and IL-21 were determined by ELISA. The mean ghrelin values were insignificantly increased in obese children compared with non-obese children. The highest blood ghrelin values were in the non-obese asthmatic group. Serum ghrelin, IL-4 and IL-21 levels were significantly increased in asthmatic children compared with non-asthmatic children (p < 0.05), and there were significant positive correlations between ghrelin and IL-4, IL-5, and IL-21 in asthmatic children. Furthermore, ghrelin, IL-4, and IL-21 levels were significantly higher in uncontrolled asthmatics compared with controlled-asthmatic children (p < 0.05). Asthma was the only significant risk factor for high ghrelin values. This study provides evidence supporting the anti-inflammatory role of ghrelin in the pathogenesis of asthma. Asthma might be considered as an important determinant of high ghrelin values in children.
Asunto(s)
Asma , Ghrelina , Interleucinas , Asma/sangre , Asma/patología , Niño , Ghrelina/sangre , Humanos , Inflamación/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Interleucinas/sangre , Obesidad/sangre , Arabia SauditaRESUMEN
BACKGROUND: Adiposity is associated with high serum levels of adipokines and chemokines which are possibly implicated in a co-existence of obesity and asthma. OBJECTIVES: Elucidate the possible roles of leptin, interleukin (IL)-4, IL-5 and IL-21 in linking obesity with childhood asthma. DESIGN: Cross-sectional, analytical. SETTING: Population of schoolchildren in a small Saudi city. SUBJECTS AND METHODS: The study included a representative sample of Saudi schoolchildren grouped as obese asthmatics, non-obese asthmatics, or obese nonasthmatics, with nonobese nonasthmatics as a control group. An asthma control test was done for the asthmatic groups. MAIN OUTCOME MEASURES: Serum levels of leptin, IL-4, IL-5, and IL-21. SAMPLE SIZE: 345 male schoolchildren with a mean (SD) age of 13.0 (2.3) years. RESULTS: Median serum leptin concentrations in obese asthmatics were significantly higher than in nonobese asthmatics ( P<.001). Uncontrolled asthmatics also had significantly higher leptin levels than controlled asthmatic children ( P<.002). Leptin levels were weakly but significantly correlated with the cytokines IL-4, IL-5, and IL-21. CONCLUSIONS: Leptin may contribute to a link between obesity and childhood asthma. Differences in IL-21 levels between nonobese and obese asthmatics suggest that the co-existence of asthma and obesity increased IL-21 levels. Leptin plus some proinflammatory cytokines especially IL-21 may be potential predictors for asthma control in children. LIMITATIONS: Blood sampling at different stages of asthma might influence cytokine expression. CONFLICT OF INTEREST: None.