Browsing by Author "Fayez, Ahmed M"

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Aspirin-based organoiron dendrimers as promising anti-inflammatory, anticancer, and antimicrobial drugs
(MDPI, 10/22/2021) Abd-El-Aziz, Alaa S; Benaaisha, Maysun R; Abdelghani, Amani A; Bissessur, Rabin; Abdel-Rahman, Laila H; Fayez, Ahmed M; Abou El-ezz, Doaa
Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.
Beneficial effects of thymoquinone and omega-3 on intestinal ischemia/reperfusion-induced renal dysfunction in rats
(Elsevier, 2014-12) Fayez, Ahmed M; Awad, Azza S; Mona M.El-Naa, Mona M; Kenawy, Sanaa A.; El-Sayedc, Mostafa E.
Intestinal ischemia–reperfusion (II/R) is a complex phenomenon causing local and remote tissue destruction and multiple-organ dysfunction. The technique has been used by many authors to produce certain organ dysfunctions. This study is to investigate the possible beneficial effects of thymoquinone and omega-3 separately in II/R-induced renal dysfunction in rats. Sixty-four Wistar albino rats were randomly allocated into four experimental groups namely sham control, II/R control, thymoquinone and omega-3 each group pre-treated separately. II/R model was established by clamping the superior mesenteric artery (SMA) for 30 min followed by 60 min reperfusion.
Chewing gum containing repaglinide solid dispersion using mesoporous silica nanoparticles for management of diabetes mellitus: In-vitro evaluation and clinical appraisal
(Editions de Sante, 2024-02) Badawi, Noha M; Amer, Reham I; Attia, Dalia A; Fayez, Ahmed M; Dawoud, Marwa H.S
The current study aimed to formulate repaglinide solid dispersion via mesoporous silica nanoparticles (R-MSNs) as a carrier in an attempt to enhance drug solubility. Then incorporation of it in a medicated chewing gum (MCG); to enhance the drug bioavailability, for the treatment of diabetes mellitus. R-MSNs solid dispersion formulations (R-MSNs-SD) were prepared using the solvent evaporation method. The chosen formula was investigated in terms of FTIR, DSC, and XRD in addition to morphology that was studied by SEM. The results demonstrated that repaglinide was successfully loaded into the pores of MSNs. The cytotoxicity of the chosen formula was evaluated by SRB assay using a Vero cell line and the cytotoxic effect of repaglinide was found to be diminished when incorporated within MSNs. Subsequently, MCGs were formulated using the chosen R-MSNs-SD as well as pure repaglinide and tested for physical properties, content uniformity, and drug release. The results exhibited a notable improvement in the release of repaglinide from the MCG containing pure repaglinide and RMSNs-SD. A clinical investigation was further conducted on diabetic patients for MCGs containing R-MSNs-SD or pure repaglinide and compared to the marketed product where the blood glucose level was measured. MCG formulations specially the one loaded with R-MSNs-SD showed enhanced antidiabetic activity than the marketed product suggesting a promising oral antidiabetic delivery system for repaglinide.
Evaluation of the hepatoprotective activity of Pulicaria incisa subspecies candolleana and in silico screening of its isolated phenolics
(Elsevier, 01/12/2021) Bakr, Riham O; Shahat, Esraa A; Elissawy, Ahmed E; Fayez, Ahmed M; Eldahshan, Omayma A
Ethnopharmacological relevance Pulicaria incisa sub. candolleana E. Gamal-Eldin (Asteraceae) was traditionally used by Bedouins as a refreshing tea and as hypoglycemic, in gastrointestinal ailments, sinusitis and headache. Recently a great correlation has been established between liver cirrhosis and gastrointestinal dysfunction reflected by abdominal bloating, pain, diarrhea, constipation, besides decreased food intake. So far, the hepatoprotective effect of P. incisa sub. candolleana E. Gamal-Eldin was not studied before although other Pulicaria species have previously shown hepatoprotective and antioxidant effects. Aim of the study In this study, we aimed to identify the phytochemical constituents of the P. incisa sub. candolleana E. Gamal-Eldin hydroethanolic extract (PICE), as well as to evaluate the hepatoprotective, anti-inflammatory and antioxidant activities in methotrexate (MTX)- intoxicated rats. Besides, the molecular interaction between the isolated compounds and cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) were assessed by in-silico screening. Material and Methods The main phytoconstituents were characterized using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Vacuum liquid chromatography (VLC) aided by preparative high-performance liquid chromatography (HPLC) were also used to isolate the major phenolics from the hydroethanolic extract. Their structures were elucidated using different spectroscopic analysis methods, including 1D and 2D nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI/MS). The hepatoprotective activity of three doses (100, 250, 500 mg/kg) of PICE in MTX-intoxicated rats was assessed and compared to silymarin as a standard. Additionally, in silico docking study on cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) was performed to justify the anti-inflammatory activity of the isolated compounds. Results Thirteen compounds were tentatively identified, including flavonoids and phenolic acids. Four main isolated compounds were identified as, eugenol-1-O-β-glucoside, 5-O-caffeoylquinic acid, 3, 5-di-O-caffeoylquinic acid and quercetin-3-O-β-glucoside. Treatment of MTX-intoxicated rats with the 250 mg/kg extract reversed the altered levels of biochemical markers of liver damage, ameliorated the oxidant status and reduced the inflammatory mediators, similar to treatment with silymarin. Quercetin-3-O-β-glucoside showed the best docking energy score of -19.12 kcal/mol against COX-2, forming four binding interactions with residues Leu 353, Arg 121, Tyr 356 and Ala 528, followed by 3,5-di-O-caffeoylquinic acid (-18.01 kcal/mol). Conclusion This study reveals P. incisa sub. candolleana as a rich source of phenolics including flavonoids, supporting its anti-inflammatory and hepatoprotective effects and suggesting its usage as a promising candidate in inflammatory conditions.
Morin post-treatment surpassed calpeptin in ameliorating 3-NP-induced cortical neurotoxicity via modulation of glutamate/calpain axis, Kidins220, and BDNF/TrkB/AKT/CREB trajectory
(Elsevier, 2023-03) Mohamed, Ola E; Abdallah, Dalaal M; Fayez, Ahmed M; Mohamed, Reem A; El-Abhar, Hanan S
The neuroprotective capacity of morin hydrate (MH), a potent antioxidant flavonoid, and calpeptin (CP), a calpain inhibitor, was documented against different insults but not Huntington’s disease (HD). Accordingly, we aim to assess the neuroprotective potential of MH and/or CP in a 3-nitropropionic acid (3-NP)-induced HD model. The 3-NP-treated rats were post-treated with saline, MH, CP, or MH + CP for a week. Post-treatment with MH and/or CP amended motor function (beam walking test) and short-/ long-term spatial memory (novel object recognition test) and improved cortical microscopic architecture. On the molecular level, MH, and to a lesser extent CP, inhibited the cortical content/expression of glutamate, calpain, and Kidins220 and abated the in- flammatory molecules, nuclear factor (NF)-κB, tumor necrosis factor-α, and interleukin-1β, as well as lipid peroxidation. However, MH, but barely CP, activated the molecules of the neuroprotective trajectory; viz., brain- derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (TrkB), protein kinase B (AKT), and cAMP response element-binding protein (CREB). Compared to the single treatments, the combination regimen mediated further reductions in the cortical contents of glutamate, calpain, and Kidins220, effects that extended to entail the anti-inflammatory/anti-oxidant potentials of MH and to a greater extent CP. However, the combination of MH strengthened the fair effect of CP on the survival signaling pathway BDNF/TrkB/AKT/CREB. In conclu- sion, MH, CP, and especially their combination, afforded neuroprotection against HD through curbing the glutamate/calpain axis, Kidins220, as well as NF-κB-mediated neuroinflammation/oxidative stress, besides activating the BDNF/TrkB/AKT/CREB hub that was partly dependent on calpain inhibition.
Neuroprotective effects of Sophora secundiflora, Sophora tomentosa leaves and formononetin on scopolamine-induced dementia
(Taylor and Francis Ltd, 7/22/2020) Aly, Shaza H; Elissawy, Ahmed M; Fayez, Ahmed M; Eldahshan, Omayma A; Elshanawany, Mohamed A; Singab, Abdel Nasser B
Five flavonoids were isolated from the ethyl acetate fraction of leaves of Sophora secundiflora; formononetin (1), 5-hydroxy-4'-methoxyflavone (2), genistein (3), 5-hydroxy-8-(1-hydroxy-1-methyl-ethyl)-2-(4-hydroxyphenyl)-4H-furo-[2, 3-h]-chromen-4-one (4) and ononin (5). Additionally, LC-ESI-MS/MS analysis of the ethyl acetate fraction of S. secundiflora leaves had led to tentative identification of eighteen compounds. Formononetin, S. tomentosa and S. secundiflora leaves methanolic extract were evaluated in vivo for their neuroprotective activity where formononetin and S. tomentosa showed promising neuroprotective activity with reduction in acetylcholine esterase (AchE) enzyme activity and elevation of acetylcholine (Ach) and glutathione(GSH) brain levels and attenuation of dopamine (DA), nor-adrenaline (NA) and malonedialdehyde (MDA) brain level significantly, However S. secundiflora leaves methanolic extract didn't attenuate the AchE enzyme activity, DA and NA brain levels
Neuroprotective effects of zafirlukast, piracetam and their combination on L‐Methionine‐induced vascular dementia in rats
(SFPT, 2019-12) Hassan, Omar; Bahnasawy, Nada H; Elnoby, Ahmed S; Fayez, Ahmed M
Vascular dementia is considered a vascular cognitive impairment disease caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress and endothelial dysfunction are the main pathogenic factors in vascular dementia. This current study aims to determine the possible neuroprotective effects of zafirlukast, piracetam and the combination of piracetam and zafirlukast on L‐methionine‐induced vascular dementia in rats. Male Wistar albino rats were divided into five groups. Group I was the normal control, and group II received L‐methionine (1700 mg/kg, P.O.) for 32 days. The remaining groups received zafirlukast (20 mg/kg, P.O.), piracetam (600 mg/kg, P.O.) or their combination (zafirlukast 20 mg/kg + piracetam 600 mg/kg, P.O.) for 32 days after L‐methionine administration. Afterwards, the cognitive and memory performances of the rats were investigated using the novel object recognition (NOR) test; rats were then sacrificed for histopathological and biochemical analyses. L‐methionine‐induced vascular dementia altered rats’ behaviours and the brain contents of different neurotransmitters and acetylcholinesterase activity while increasing levels of oxidative stress and causing notable histopathological alterations in brain tissues. The treatment of vascular dementia with zafirlukast and the combination improved neurochemical, behavioural and histological alterations to a comparable level to those of piracetam. Thus, zafirlukast, piracetam and the combination of both drugs can be considered as potential therapeutic strategies for the treatment of vascular dementia induced by L‐methionine. To the best of our knowledge, this study is the first to explore the neuroprotective effects of zafirlukast and piracetam on L‐methionine‐induced vascular dementia
Optimization of nanovesicular carriers of a poorly soluble drug using factorial design methodology and artificial neural network by applying quality by design approach
(Taylor and Francis Ltd., 09/12/2021) Dawoud, Marwa H.S; Fayez, Ahmed M; Mohamed, Reem A; Sweed, Nabila M
The aim of the current work is to utilize quality by design (QbD) approach to develop and optimize nanovesicular carriers of a hydrophobic drug. Rosuvastatin calcium was used as a model drug, which suffers poor bioavailability. Several tools were used in the risk assessment study as Ishikawa diagrams. The critical process parameters (CPP) were found to be the particle size, polydispersity index, zeta potential and entrapment efficiency. Factorial design was used in risk analysis, which was complemented with artificial neural network (ANN); to assure its accuracy. A design space was established, with an optimized nanostructured lipid carrier formula containing 3.2% total lipid content, 0.139% surfactant and 0.1197 mg % drug. The optimized formula showed a sustained drug release up to 72 hours. It successfully lowered each of the total cholesterol, low density lipoprotein and triglycerides and elevated the high-density lipoprotein levels, as compared to the standard drug. Thus, the concurrent use of the factorial design with ANN using QbD approach permitted the exploration of the experimental regions for a successful nanovesicular carrier formulation, and could be used as a reference for many nanostructured drug delivery studies during their pharmaceutical development and product manufacturing.
Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats
(Springer, 7/13/2021) Amer, Reham I; Yassin, Ghada E; Mohamed, Reem A; Fayez, Ahmed M
Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (− 31.4 to − 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP- NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.
Progression of hepatic encephalopathy induced by bile duct ligation versus thioacetamide in rats: Regulatory role of apigenin
(Open Science Publishers LLP Inc., 2021-12) Fayez, Ahmed M; Mansour, Dina F; Saleh, Dalia O
Hepatic encephalopathy (HE) is the decline in brain functions due to liver insufficiency. A high mortality rate was reported due to the rapid progression of HE from covert to overt, leading to detrimental consequences. This study aims to assess the progression of HE and the potential hepatoprotective and neuroprotective effect of apigenin (APG) in bile duct ligation (BDL) versus thioacetamide (TAA)-induced HE models in rats. Wistar albino rats were divided into eight groups; four groups for the BDL model and the other four groups for the TAA model (100 mg/kg, i.p., thrice weekly for five consecutive weeks). APG (20 mg/kg/day) or lactulose (LAC) (8 ml/kg/day), as the standard, was administered orally for three consecutive weeks starting from day 14 of the experiment. Liver enzymes, total bilirubin, serum ammonia, brain and liver glutathione and malondialdehyde, brain dopamine, hepatic interleukin-6, and nuclear factor kappa B were assessed, as well as the beam walking test and histopathological examinations were carried out. APG showed significant anti-hyperammonemic, anti-oxidant, and anti-inflammatory effects in HE groups. Additionally, improvement in behavioral test and histological image of livers and brains of HE rats treated with APG was observed. In conclusion, APG exerted a significant regulatory role compared to LAC in progression of HE in BDL and TAA models. © 2021. Ahmed M. Fayez et al. All Rights Reserved.
Thioacetamide-induced acute hepatic encephalopathy: central vs peripheral effect of Allicin
(Springer, 3/25/2021) Saleh, Dalia O; Mansour, Dina F; Fayez, Ahmed M
Hepatic encephalopathy (HE) is a debilitating and life-threatening disease. Results from acute or chronic liver failure and is characterized by abnormal cerebral and neurological alterations. This study aimed at investigating the effect of allicin, the major functional component in freshly crushed garlic extract, on thioacetamide (TAA)-induced HE in rats. Induction of HE by a single dose of TAA (300 mg/kg; I.P.) was associated with a marked elevation in the serum levels of alanine amino- transferase, aspartate aminotransferase, bilirubin, albumin, total protein, blood urea nitrogen and serum ammonia besides reduction in the serum level of albumin. Moreover, it was accompanied with an increase in the hepatic and brain levels of inflammatory mediators; TNF-α and IL-1β as well as elevation of the hepatic and brain levels of oxidative stress biomarkers; reduced glutathione and lipid peroxidation evidenced by malondialdeyde. Oral administration of allicin (50, 100 and 200 mg/kg; P.O.) for 6 days prior to TAA injection restored the serum liver function, hepatic and brain levels of inflamma- tory mediators as well as oxidative stress biomarkers in a dose-dependent manner. From our results, it can be concluded that allicin has a protective effect on TAA-induced HE in rats in a dose-dependent manner due to its powerful antioxidant and anti-inflammatory properties.
Uro-protective role of chrysin against cyclophosphamide-induced hemorrhagic cystitis in rats involving the turning-off NF-κB/P38-MAPK, NO/PARP-1 and STAT-3 signaling cascades
(Elsevier Ireland Ltd, 2023-05) Saleh, Dalia O; Abo El Nasr, Nesma M.E; Fayez, Ahmed M; Ahmed, Kawkab A; Mohamed, Reem A
Chemico-Biological Interactions Available online 30 May 2023, 110585 In Press, Journal Pre-proofWhat’s this? Research paper Uro-protective role of chrysin against cyclophosphamide-induced hemorrhagic cystitis in rats involving the turning-off NF-κB/P38-MAPK, NO/PARP-1 and STAT-3 signaling cascades Author links open overlay panelDalia O. Saleh a, Nesma M.E. Abo El Nasr a, Ahmed M. Fayez b, Kawkab A. Ahmed c, Reem A. Mohamed d a Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt b Pharmacology and Toxicology Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt c Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt d Department of Pharmacology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt Received 2 March 2023, Revised 6 May 2023, Accepted 29 May 2023, Available online 30 May 2023. Show less Outline Share Cite https://doi.org/ Background Chemotherapeutic agents are used to treat a wide range of cancer types, but they cause serious side effects which must be managed after treatment. Cyclophosphamide (CYP) is one of chemotherapeutic drugs that causes hemorrhagic cystitis (HC) induced by acrolein. Objective The current investigation intended to uncover the role of chrysin (CHR) in CYP-induced HC in rats and explore the signaling pathway beyond this effect. Analysis process: A single dose of CYP (200 mg/kg/IP) was injected, meanwhile CHR (25, 50 and 100 mg/kg, P.O) was administered respectively for 7 days prior to CYP administration and resume for 7 days afterwards. Urinary bladder tissue was then isolated from all rats to assess oxidative stress and inflammatory biomarkers. Moreover, histopathological examinations were performed. Results Treatment with CHR showed a marked alleviation in oxidative stress biomarkers induced by CYP. Furthermore, CHR treatment presented a dose-dependent boost in the anti-inflammatory; IL-10 levels and a drop in the pro-inflammatory biomarkers; IL-1β, IL-6, and TNF–α. Additionally, stabilization of the PARP-1 protein expression was also detected thus preventing DNA damage. Similarly, CHR restored the urinary bladder cGMP levels. Notably, CHR treatment was accompanied with inhibition in NF-κB/p38-MAPK, NO/PARP-1 and STAT-3 signaling pathways inflammatory cascades. All these findings conformed with the histopathological examinations as well as iNOS immunostaining in the urinary bladder tissue. Conclusion Co-administration of CHR and CYP attained uro-protective therapeutic potential to guard against HC as well as spot the tangled mechanism of CHR in attenuating the HC induced by CYP.