Changes in gut microbiota of alloxan-induced diabetic rats in response to orally administered combined aqueous extracts of olive leaves and ginger
Authors : Shatha Alshaer, Feras Darwish El-Hajji , Reem Abu-Tayeh , Iman Basheti , Mohammad A. A. Al-Najjar
Abstract : Olive leaves and ginger rhizomes are examples of medicinal plants that have been used, separately, for the management of different ailments. Diabetes mellitus is a chronic disease that is prevalent around the whole world and is significant among adults in Middle Eastern countries. The effect of the combined mixture of olive leaves and ginger rhizome aqueous extracts has not been previously studied for its hypoglycemic effect, nor for its effect on gut microbiota in the diabetes-induced rat model. This study aims to elucidate the potential effect of the orally ingested combination of the aqueous extract of olive leaves and ginger rhizome on the gut microbiota in both healthy and diabetic rats. Diabetes was induced by intraperitoneal injection of alloxan monohydrate, and the aqueous extracts were prepared in the same homemade preparation method. Each extract and subsequent combination were given separately at a dose of 500 mg/kg per day, with or without insulin (6 IU/kg) for 7 days, to every rat in the different groups. Fasting blood glucose was carried out to evaluate the diabetic state, and fecal samples were collected at different time points for 16s rRNA gene sequencing. The combination of extracts increased bacterial diversity in general and raised the Firmicutes/Bacteroidetes ratio in both healthy and diabetic rats. Moreover, while it increased the relative abundance of Lactobacillus and Prevotella, it decreased the relative abundance of Clostridium and Bacteroides in healthy rats. These results have positive effects on the management of diabetes, by increasing short-chain fatty acid production, which can suppress the appetite and prevent damage to pancreatic cells. This study underlines the additional benefits of using herbal extracts to retain dysbiosis and improve gut microbiota
Keywords : Diabetes mellites, gut microbiota, olive leaves extracts, ginger rhizome extract, prebiotic effect, short-chain fatty acid production
Visit
A systematic review of randomized controlled trials assessing phytochemicals and natural ingredients for skin and hair care
Authors : Samar Thiab, Nizar M. Mhaidat, May Abu Taha, Sarah Thiab, Somaya Koraysh, Reem Abutayeh, Iman Basheti
Abstract : Cosmetics are marketed and used worldwide for various purposes. Several natural products are used for the development of cosmetic preparations. This paper systematically reviews randomized controlled trials (RCTs) investigating plant extracts, herbal preparations, and isolated plant-derived compounds used particularly for skin and hair care. Two independent electronic searches were conducted through PubMed and EMBASE to identify eligible RCTs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Data extraction was performed independently by four authors based on standardized extraction forms. The risk of bias was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials. Sixty-three RCTs were identified; 53 were using natural products for skin care and 10 for hair care. The results were summarized in tables including the population, type of intervention, comparisons with placebo or other natural products, outcomes reported, follow-up period (P: Patient, Population; I: Intervention; C: Comparison (or Control); O: Outcome; T: Time), and country in which the study was conducted. Ten plants were identified to be present in different locations in Jordan by referring to the Royal Botanic Gardens’ publication, titled “The Plants of Jordan: An Annotated Checklist.” Some plants were found to have promising findings requiring further investigations in bigger RCTs with robust design and adequate reporting.
Keywords : skin care, hair care, natural cosmetics, randomized controlled trials
Visit
Evaluation of the orally administered calcium alginate aerogel on the changes of gut microbiota and hepatic and renal function of Wistar rats
Authors : Mohammad A.A. Al-NajjarI, Tamara Athamneh, Reem AbuTayeh, Iman Basheti, Claudia Leopold, Pavel Gurikov, Irina Smirnova
Abstract : The present study evaluates the effect of calcium alginate aerogel as a potential drug carrier, on the liver and kidney functions, and on the gut microbiota of Wistar rats. The studied alginate aerogel was prepared in the form of nanoparticles using the jet cutting technique, and they were characterized in terms of specific surface areas, outer morphology and particle size distribution. For the in vivo study, calcium alginate aerogel was administered orally, and liver and kidney functions were tested for one week and for four weeks in two distinct studies. During the short-term in vivo study, feces samples were collected for bacterial DNA extraction followed by 16S rRNA gene sequencing analyses to detect changes in gut microbiota. Results showed that the prepared alginate aerogel has an average BET-specific surface area of around 540 m2/g, with a pore volume of 7.4 cc/g, and pore width of 30-50 nm. The in vivo study revealed that the levels of the studied kidney and liver enzymes didn't exceed the highest level of the normal range. The study of gut microbiota showed different patterns; certain groups of bacteria, such as Clostridia and Bacteriodia, increased during the aerogels regime and continued to increase after the aerogel was stopped. While other groups such as Erysipelotrichia, and Candidatus saccharibacteria increased during aerogels treatment, and then decreased again after one month. Members of the Bacilli class showed a unique trend, that is, after being the most abundant group (63%) at time 0, their relative abundance decreased dramatically until it reached < 5%; which was the case even after stopping the aerogel treatment.
Keywords :
Visit
Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA)
Authors : Hijjawi, Majd S., Reem Fawaz Abutayeh, and Mutasem O. Taha
Abstract : Aurora-A kinase plays a central role in mitosis, where aberrant activation contributes to cancer by promoting cell cycle progression, genomic instability, epithelial-mesenchymal transition, and cancer stemness. Aurora-A kinase inhibitors have shown encouraging results in clinical trials but have not gained Food and Drug Administration (FDA) approval. An innovative computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA) was applied-aiming to identify novel Aurora-A kinase inhibitors-using seventy-nine reported Aurora-A kinase inhibitors to specify the best possible docking settings needed to fit into the active-site binding pocket of Aurora-A kinase crystal structure, in a process that only potent ligands contact critical binding-site spots, distinct from those occupied by less-active ligands. Optimal dbCICA models were transformed into two corresponding pharmacophores. The optimal one, in capturing active hits and discarding inactive ones, validated by receiver operating characteristic analysis, was used as a virtual in-silico search query for screening new molecules from the National Cancer Institute database. A fluorescence resonance energy transfer (FRET)-based assay was used to assess the activity of captured molecules and five promising Aurora-A kinase inhibitors were identified. The activity was next validated using a cell culture anti-proliferative assay (MTT) and revealed a most potent lead 85(NCI 14040) molecule after 72 h of incubation, scoring IC 50 values of 3.5-11.0 µM against PANC1 (pancreas), PC-3 (prostate), T-47D and MDA-MB-231 (breast)cancer cells, and showing favorable safety profiles (27.5 µM IC 50 on fibroblasts). Our results provide new clues for further development of Aurora-A kinase inhibitors as anticancer molecules.
Keywords : Aurora-A kinase; aurora inhibitors; AURKA; structure-based drug design; docking-based comparative intermolecular contacts analysis; molecular docking; in-silico screening; MTT assay; PANC1; PC-3; T-47D; MDA-MB-231
Visit
Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation
Authors : Talib, Wamidh H., Izzeddin Alsalahat, Safa Daoud, Reem Fawaz Abutayeh, and Asma Ismail Mahmod.
Abstract : Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.
Keywords : alternative anticancer therapies; natural products; plant extracts; curcumin; thymoquinone
Visit
Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors
Authors : Abutayeh, Reem F., Jehad Almaliti, and Mutasem O. Taha
Abstract : Background: Flt3 is an oncogenic kinase involved in different leukemias. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML. Methods: The crystallographic structures of two inhibitors complexed within Flt3, namely, quizartinib and F6M, were used to guide the synthesis of new sulfonamide-based Flt3 inhibitors. Results: One of the prepared compounds showed low micromolar anti-Flt3 bioactivity, and interestingly, low micromolar bioactivity against the related oncogenic kinase VEGFR2. Conclusion: Sulfonamides were successfully used as privileged scaffolds for the synthesis of novel Flt3 inhibitors of micromolar potencies.
Keywords : Acute Myeloid Leukemia; F6M; Flt3; Quizatrinib; Sulfonamides; VEGFR2
Visit
Discovery of novel Flt3 inhibitory chemotypes through extensive ligand-based and new structure-based pharmacophore modelling methods
Authors : Abutayeh, Reem Fawaz, and Mutasem O. Taha
Abstract : Flt3 is an oncogenic kinase involved in different types of leukemia. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML prompting us to model this interesting target. We implemented ligand-based, QSAR-guided, pharmacophore exploration combined with novel structure-based computational workflow based on docking-based comparative intermolecular contacts analysis (db-CICA) combined with homology modelling to explore the pharmacophoric features of 93 diverse cyclic Flt3 inhibitors. The resulting pharmacophore models were used as virtual search queries to scan the National Cancer Institute (NCI) database for novel Flt3 inhibitory leads. Ten hits of novel scaffolds were captured showing anti-Flt3 IC50 values ranging from 1.2 to 14.7 μM. Interestingly, six of them illustrated low micromolar and submicromolar potencies against the mutated active form of Flt3 (Flt3D835Y) and the related vascular endothelial growth factor receptor 2 (VEGFR2). Keywords: Flt3 Pharmacophore QSAR MLR kNN Homology modelling db-CICA In vitro assay.
Keywords :
Visit
: Pharmacokinetic evaluation of D-ribose after oral and intravenous administration to healthy rabbits.
Authors : Alzoubi, Karem H., Zuhair Bani Ismail, Mohamed K. Al-Essa, Osama Y. Alshogran, Reem F. Abutayeh, and Nareman Abu-Baker
Abstract : Introduction: This study explored d-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods: D-ribose was administered once as 420 mg/kg (N=4) or 840 mg/kg (N=6) dose intravenously, or as an oral dose of 420 mg/kg (N=3) or 840 mg/kg (N=3). Serum was obtained at various time points, up to 210 minutes after administration. Urine was also collected after IV administration. Pharmacokinetic parameters were determined from drug concentration–time data using Kinetica software. Results: The findings showed that D-ribose follows a dose-dependent kinetic profile. With doubling the IV dose, AUCtotal was significantly increased by threefold, while the clearance was decreased by 44%. The half-life was 1.7-fold longer at the higher dose. Similar nonsignificant trends were also observed at oral administration. D-ribose was rapidly absorbed (Tmax=36–44 minutes) and rapidly disappeared from plasma (within <140 minutes). Additionally, D-ribose was partially (18–37.5%) recovered from urine. Conclusion: Collectively, D-ribose showed a dose-dependent kinetic profile, where parameters change according to dosing levels. D-ribose clearance seems to follow first-order kinetics at low dose. Thereafter, elimination systems are saturated, and elimination continues in a fast manner. Urine recovery was partial, which could be attributed to the several metabolic pathways that pentose can undergo.
Keywords : D-ribose, single dose, pharmacokinetics, rabbits, oral, intravenous.
Visit
Novel anticancer compound [trifluoromethyl-substituted pyrazole N-nucleoside] inhibits FLT3 activity to induce differentiation in acute myeloid leukemia cells
Authors : Saleh, Ayman M., Mutasem O. Taha, Mohammad A. Aziz, Mahmoud A. Al-Qudah, Reem F. AbuTayeh, and Syed A. Rizvi
Abstract : Anticancer properties of chemically synthesized compounds have continuously been optimized for better efficacy and selectivity. Derivatives of heterocyclic compounds are well known to have selective antiproliferative effect against many types of cancer. In this study, we investigated the ability of an indigenously synthesized anticancer molecule, G-11 [1-(2”,3”,4”,6”-Tetra-O-acetyl-β-D-glucopyranosyl)-4-(3'-trifluoromethylphenylhydrazono)-3-trifluoromethyl-1,4-dihydropyrazol-5-one], to cause selective cytotoxicity and induce differentiation in the acute myeloid leukemia HL-60 cells. G-11 was able to exert cytotoxic effect on hematological (Jurkat, U937, K562, HL-60, CCRF-SB) and solid tumor (MCF-7, HepG2, HeLa, Caco-2) cell lines, with IC50 values significantly lower than noncancerous cells (HEK-293, BJ and Vero) and normal peripheral blood mononuclear cells. G-11 induced differentiation of HL-60 cells to granulocytes and monocytes/macrophages by inhibiting the activation of FLT3 (CD135 tyrosine kinase). ITD-FLT3 mutation found in many acute myeloid leukemia patients could also be targeted by G-11 as exhibited by its inhibitory effect on MOLM-13 and MV4-11 cell lines. Molecular docking studies suggest the involvement of Leu616, Asp698, Cys694 and Cys828 residues in binding of G-11 to FLT3. The ability of G-11 to cause selective cytotoxicity and induce differentiation in cancer cells could be clinically relevant for therapeutic gains.
Keywords : Heterocyclic compound Trifluoromethyl-substituted pyrazole N-nucleosides Anticancer Acute myeloid leukemia (AML) Cell differentiation FLT3
Visit
Evaluation of α-D-ribofuranose (D-ribose) toxicity after intravenous administration to rabbits
Authors : Ismail ZB, Abu-Baker N, Alzoubi K, Al-Zhgoul M, Al-Essa MK, Khlouf S, Al-Saleh A, Al-Omari B, Abu-Tayeh R, Shomaf M, Battah A.
Abstract : Rapid intravenous administration of d-ribose may result in a significant reduction in cellular damage in patients with sudden ischemic insults. The development of an effective and clinically safe therapeutic regimen using the intravenous route in critically ill patients especially with cardiac diseases requires a comprehensive assessment of potential toxic effects of the drug in laboratory animals and in human beings. The potential clinical, behavioral, hematological, biochemical, gross pathological and histological toxic effects associated with the intravenous administration of d-ribose in rabbits for 28 days were evaluated in this study. Except for an increase in neutrophil percentage in male rabbits in the d-ribose-treated groups, there were no statistically significant toxic effects induced by daily intravenous administration of the drug in male and female rabbits. Results of this study suggest that d-ribose administered intravenously for 28 days in the rabbit exhibited no toxicity at 420 mg/kg.
Keywords : d-Ribose, rabbits, side effects, subacute toxicity, intravenous injection
Visit
Poisoning in Jordan: Analysis of Three Year Data from Jordan National Drug and Poison Information Center
Authors : Obeidat, Nathir M., Reem F. Abutayeh, and Kamal A. Hadidi
Abstract : Objectives: This study aims at analyzing the patterns of poisoning cases reported to the Jordan National Drug and Poison Information Center and emphasizes the roles and challenges faced by the center from a practical perspective. Materials and Methods: A retrospective analysis of a three year period 2006-2008 was conducted depending on the data collected by the center. Results: Analysis of data shows that a total of 914 inquiries were received by the center during the study period. More than 90% of the enquiries were from health care providers and 3.6% from the public that included victims and victims' relatives. The exposed population age ranged from less than 1 year to 80 years, with the highest incidence in children less or equal to 5 years (34.9%). The most common reason of poisoning was unintentional (49.39%), followed by suicidal attempts (23.94%). The highest incidence of poisoning was due to drugs which accounted for more than 42% of all exposures, where acetaminophen products were responsible for most of the cases within this category (13.4%). Conclusion: The poisoning features in Jordan reflect mostly the incidences of poisoning within Amman - the capital of Jordan - in addition to other major cities in the country. Yet the center seeks more perception from the public, support from healthcare providers and verification from related governmental parties, which will enable the center to fulfill its duties according to international standards.
Keywords : Poisoning, Information, Jordan
Visit