Faculty Of Pharmacy Research Paper

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    A sustainable and green HPLC-PDA technique for the simultaneous estimation of Post-COVID-19 syndrome co-administered drugs with greenness and whiteness assessment
    (Nature Publishing Group, 2024-10-01) Passant M. Medhat; Manal Mohamed Fouad; Hany H. Monir; Nermine S.Ghoniem
    COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10–15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors’ quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00–45.00 µg/mL, 0.5–50.00 µg/mL, and 0.15–20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55–99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method’s greenness. “Non-toxic” ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method’s greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.
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    Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies
    (Academic Press Inc, 2024-11-02) Eman R. Mohammed; Manal Abdel Fattah Ezzat; Emad M. Seif; Basma M. Essa; Hatem A. Abdel-Aziz; Tamer M. Sakr; Hany S. Ibrahim
    Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.
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    Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3β/CREB Curbing Neuroinflammation
    (Wiley Online Library , 2024-09-26) Doaa Abou El-ezz; Waleed Aldahmash; Tuba Esatbeyoglu; Sherif M. Afifi; Marawan Abd Elbaset
    Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1–42 (Aβ1-42) and p-tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-κB levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.
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    Aspirin-based Organoiron Dendrimers as Promising Anti-inflammatory, Anticancer, and Antimicrobial Drugs.
    (Multidisciplinary Digital Publishing Institute (MDPI), 2021-10-22) Maysun Ramadan; Amani Anwar Abdelghani; Laila H. Abdelrahman; Rabin Bissessur
    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.
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    A comparative UPLC‑orbitrap‑MS‑based metabolite profiling of three Pelargonium species cultivated in Egypt
    (Springer Nature, 2024-10-01) Rana M. Merghany; Mohamed A. Salem; Shahira M. Ezzat; Sherifa F. A. Moustafa; Salma A. El‑Sawi; Meselhy R. Meselhy
    Several Pelargonium species are cultivated mainly to produce essential oils used in perfume industry and for ornamental purposes. Although the chemical composition and biological activities of their essential oils were extensively investigated, there is limited information about the chemical composition of their non-volatile constituents. In this study, we report an Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)-based metabolomics approach for the annotation and analysis of various metabolites in three species; P. graveolens, P. denticulatum, and P. fragrans utilizing The Global Natural Product Social Molecular Networking (GNPS) and multivariate data analyses for clustering of the metabolites. A total of 154 metabolites belonging to different classes were annotated. The three species are good sources of coumarins, benzoic acid derivatives, organic acids, fatty acids, and phospholipids. However, the highest level of flavonols (mono- and di-O-glycosides) and cinnamic acid derivatives was found in P. graveolens and P. denticulatum, whereas tannins and flavone C-glycosides were abundant in P. fragrans. The metabolic profiles clarified here provide comprehensive information on the non-volatile constituents of the three Pelargonium species and can be employed for their authentication and possible therapeutic applications.
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    Formulation and characterization of tea tree and jojoba oils nano-emulgel for in-vivo wound healing assessment
    (Elsevier B.V, 2025-01-01) Nehal Kh. Mohamed; Asmaa A. Metwally; Sally M.Y. Fared; A. Farid; Mohamed Taha
    Cutaneous wounds are the most common surgical affections among living organisms worldwide, and their healing may be interrupted by several factors. This study aimed to formulate and evaluate the antioxidant, anti-inflammatory, and antimicrobial activity of tea tree and jojoba oils nano-emulsions, additionally, investigating the cytotoxicity of the optimized formula was investigated on normal human lung fibroblast cells (WI-38) by MTT colorimetric assay, additionally its in-vivo wound healing. Nano-emulsions (NEs) were prepared using a high-energy method and characterized by Transmission electron microscopy (TEM), Zeta potential, droplet size, and poly dispersive index (PDI). Nano-emulgel (NEG) was formulated by mixing the standard NE with carbopol® 940. For in-vivo wound healing, thirty adult female albino rats were assigned into control, moist exposed burn ointment (Mebo), and NEG-treated groups. The healing was assessed by analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and histopathology in healed wound tissues. All formulations demonstrated antioxidant, anti-inflammatory, and antimicrobial activity against Bacillus Subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Enterococcus faecalis, and Candida albicans. The CC50 of the optimized formula was 453.82± 3.87 µg/mL, with a mean droplet size of 105.4 nm and a zeta potential of −39.2 ± 2.1 mV. NEG enhanced wound closure compared to Mebo-treated and control groups. Also, MDA significantly decreased and SOD significantly increased in NEG and Mebo-treated groups compared to the control (p ˂ 0.05). TNF-α, and IL-1β significantly decreased in NEG and Mebo-treated compared to the control (p < 0.05). Histopathology revealed reduced inflammatory cell infiltration, rapid epithelization, and increased collagen deposition in NEG-treated wound tissues compared to the control and Mebo-treated wounds. In conclusion, the NEG containing tea tree and jojoba oils demonstrated significant antioxidant, anti-inflammatory, antimicrobial, and wound healing activities.
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    Molecular insight of miRNA-217 role in the pathogenesis of myocardial infarction: Promising diagnostic biomarker and therapeutic target
    (KeAi Communications Co., 2025-02-01) Mai A. Zaafan; Amr M. Abdelhamid
    Background: Globally, myocardial infarction (MI) is one of the main causes of death. This study aims to investigate the role of miR-217 in the pathogenesis through targeting MAPK and PI3K/AKT signaling pathways in experimental model of myocardial infarction and studying the possible cardioprotective role of dihydromyricetin (DHM) through modulation of this pathway. Methods: Dihydromyricetin was injected (100 mg/kg; p.o.) in isoprenaline induced myocardial infarction rat model for 14 days. Rats were anaesthetized and blood samples were taken for serum separation, estimation of creatine kinase-MB (CK-MB), and troponin-I levels after 24 h had passed since the last isoprenaline injection. In addition, the hearts were also used for the other biochemical studies and the histological evaluation. Results: DHM resulted in a significant suppression of the elevated levels miR-217 and MAPK compared to the MI control group and restored the normal level of serum CK-MB. Furthermore, DHM successfully restored the oxidative balance and halted the pro-inflammatory mediators in the cardiac tissue. Conclusion: Accordingly, our experiment emphasizes the anti-ischemic property that has been demonstrated through modulation of expression level of miR-217 and consequent deactivation of MAPK and PI3K/AKT signaling pathways, and this was assured by halting downstream pro-inflammatory markers.
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    Computational metal-flavonoids complexes presentation of greenly synthesized silver nanoparticles combined flavonoids from Lens culinaris L. as anticancer agents using BcL-2 and IspC proteins
    (Taylor and Francis Ltd, 2024-10-01) Heba W. Alhamdi; Fatma Alzahraa Mokhtar; Fouad Lamghari Ridouane; Ali A. Shati; Serag Eldin I. Elbehairi; Lamiaa I. Fahmy; Mohammad Y. Alfaifi; Nada K. Sedky; Heba A. Fahmy
    Lens culinaris L., has been widely recognized for its medical applications. LC-ESI-TOF-MS identified 22 secondary metabolites including phenolics, flavonoids, and anthocyanidin glycosides among its total extract (LCTE). The study aimed to apply LCTE as a biogenic material for reducing and capping the silver nanoparticles (LC-AgNPs). The ynthesized LC-AgNPs were characterized using different techniques. The UV absorption was observed at λmax 379 nm. LC-AgNPs were spherical, with 19.22 nm average size. The face cubic centre nature was demonstrated by HR-TEM and XRD. The LC-AgNPs were then evaluated for their anticancer and antimicrobial potentials. LC-AgNPs showed an extremely potent cytotoxic activity against MCF-7, HCT-116 and HepG2 cell lines (IC50= 0.37, 0.35 and 0.1 µg/mL, respectively). LC-AgNPs induced significant apoptotic effects in the three examined cancer cell lines. LC-AgNPs resulted in sequestration of cells in G1 phase of the cell cycle in both MCF-7 and HCT-116 cells, meanwhile it trapped cells at the G2 phase in HepG2 cells. Moreover, the antimicrobial activity of LC-AgNPs was highly confirmed against Klebsiella pneumoniae and Acinetobacter baumannii. Molecular docking study designated Kaempferol-3-O-robinoside-7-O-rhamnoside and Quercetin-3-D-xyloside as the topmost LCTE active constituents that caused inhibition of both Bcl-2 and IspC cancer targets in combination with the produced silver nanoparticles.
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    Enhancing oral cancer treatment via photodynamic therapy: Gold nanoparticle-based delivery system for 5-aminolevulinic acid (5-ALA)
    (Published by Elsevier Ltd, 2024-09-10) Romesa Soomro; Mohamed Abdelmonem; Bachren Azra Saputra; Che Azurahanim Che Abdullah
    Oral squamous cell carcinoma (OSCC) is a significant global health concern, responsible for approximately 300,000 new cases and 145,000 deaths annually, making it the sixth most common malignancy worldwide. Traditional treatments, including surgery, radiation, and chemotherapy, often lead to severe side effects such as physical disfigurement, functional loss, and systemic toxicity. These limitations have spurred the search for alternative therapies, with photodynamic therapy (PDT) gaining recognition for its reduced invasiveness, improved targeting, and better cosmetic outcomes. However, PDT faces challenges, including inadequate photosensitizer (PS) delivery, poor specificity, and degradation in physiological environments. Nanotechnology has emerged as a promising solution to enhance PDT by improving the stability, selectivity, and therapeutic efficacy of PSs. Gold nanoparticles (AuNPs) have shown the potential to enhance PDT outcomes, particularly in OSCC, by inhibiting tumor proliferation and improving diagnostic accuracy without systemic toxicity. Despite these advancements, the conventional chemical synthesis of AuNPs poses environmental concerns, high costs, and potential biocompatibility issues. This study introduces a novel biogenic synthesis approach for AuNPs, utilizing green chemistry principles to create more biocompatible and environmentally sustainable nanoparticles. The novelty of this research lies in the application of green-synthesized AuNPs to enhance PS delivery in PDT, offering a more effective and less toxic treatment option for oral cancer. This innovative approach addresses the limitations of current PDT and nanoparticle synthesis methods, contributing to the development of more sustainable and biocompatible cancer therapies. The study's findings are contextualized within the increasing scholarly and patent activity surrounding AuNPs and 5-aminolevulinic acid (5-ALA) in cancer therapies, underscoring the growing importance of this field in advancing OSCC
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    A comprehensive review of natural compounds and their structure–activity relationship in Parkinson’s disease: exploring potential mechanisms
    (Springer Nature, 2024-10-11) Rana M. Merghany; Salma A. El‑Sawi; Asmaa F. Aboul Naser; Shahira M. Ezzat; Sherifa F. A. Moustafa; Meselhy R. Meselhy
    Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Natural compounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure–activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.
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    The antitumour efficacy of hesperidin vs. cisplatin against non‑small lung cancer cells A549 and H460 via targeting the miR‑34a/PD-L1/NF-κB signalling pathway
    (Termedia Publishing House Ltd, 2024-08) Ibrahim, Sherine M; Sayed, Maryam S; Abo-Elmatty, Dina M; Mesbah, Noha M; Abdel-Hamed, Asmaa R
    Introduction: Lung cancer is the most common type of cancer, causing worldwide mortality. Therefore, this study is necessary for continuing research into new effective and safe treatments. Recently, herbal medicines have been used for the treatment of various diseases such as cancer. This study aimed to investigate the potential anti-proliferative activity and investigate the mechanisms of hesperidin extract on the non-small lung cancer cells A549 and H460 vs. cisplatin via targeting the miR 34a/PD-L1/NF-κB signalling pathway. Material and methods: To determine the cytotoxic effects of the hesperidin extract on non-small lung cancer cells, sulphorhdamine B assay was performed. To show the inhibition of migration by hesperidin extract, wound healing assay was conducted. A quantitative polymerase chain reaction test was used to quantify the expressions of miR-34a, programmed cell death ligand-1 (PDL-1), epidermal growth factor receptor (EGFR), and P53 genes, which are involved in apoptosis pathway. Also, cell cycle assay was performed by using a flow cytometer. Results: The hesperidin extract could significantly inhibit proliferation of non-small lung cancer cells A549 and H460. Western blot assay demonstrated that hesperidin induced suppression of nuclear factor κB signalling pathway. The messenger RNA expression levels of MiR-34a and P53 were up-regulated significantly by hesperidin treatment, while the EGFR and P53 genes were down-regulated. The flow cytometer confirmed that cell cycle arrest occurred at the sub-G1 and G2 phases in A549 and H460, respectively. Conclusions: Our study demonstrated that hesperidin extract could significantly inhibit non-small lung cancer cell growth by induction of the apoptosis signalling pathway. Therefore, hesperidin might open novel strategies for effective and safe cancer treatment and reduce the adverse side effects of several chemotherapeutic treatments such as cisplatin.
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    Physalis peruviana fruit bioactive compounds
    (Elsevier, 2024-01) Ezzat, Shahira M; Salama, Maha M
    The top world producers of Physalis peruviana L. fruits are Colombia and South Africa; also it is widely cultivated in Egypt, Kenya, Zimbabwe, Ecuador, and Peru. The plant grows wild giving an edible round, small berry fruit enclosed within a papery calyx. The fruit is distinguished by producing ethylene at a high rate. P. peruviana fruits have been exclusively studied due to their nutritional and bioactive metabolites, in addition to their folk medicine uses as an antiasthmatic, diuretic, sedative, analgesic, antiinflammatory, antioxidant, antibacterial, and anticancer agents as well as in diabetes and diabetic neuropathy management. This chapter reviews the bioactive metabolites of P. peruviana that have been identified or isolated from fruits worldwide. The major metabolites reported with pharmacological activities are withanolides, carotenoids, fixed oil, and minerals in addition to phenolics—the largest class in the fruit—to which most of the biological activities are attributed.
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    Advanced Approaches in Green Univariate Spectrophotometric Methods
    (wiley, 2024-01) Lotfy, Hayam M; Saleh, Sarah S; Rostom, Yasmin; Obaydo, Reem H; Ahmed, Dina A
    The pharmaceutical industry and market have shown a tremendous evolution where different new pharmaceuticals and pharmaceutical combinations have been introduced in order to increase patient compliance and obtain the required outcomes. On the other hand, this evolution has raised a challenge in the field of drug analysis, where new applicable methods of analysis needed to be developed and validated to ensure that the right doses would reach patients free from any undesired compounds such as impurities, adulterants, or interfering substances that might lead to any undesirable side effects. This chapter highlights the advanced approaches in green univariate spectrophotometric methods based on basic mathematical techniques, such as subtraction, division, and multiplication, for assaying the components of multicomponent mixtures in their different pharmaceutical dosage forms utilising inexpensive, affordable, and eco-friendly facilities.
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    Insight on Some Newly Synthesized Trisubstituted Imidazolinones as VEGFR-2 Inhibitors
    (American Chemical Society, 2024-06) Mohamed, Manar R; Mahmoud, Walaa R; Refaey, Rana H; George, Riham F; Georgey, Hanan H
    Two series of ten new 1,2,4-trisubstituted imidazolin-5-ones were synthesized and screened against MCF-7 breast cancer and A549 lung cancer cell lines to test their potential in vitro anticancer activity. The results revealed preferential activity of the tested compounds toward MCF-7 cell lines compared to A549 cell lines. The most promising ten compounds (3a, 3c, 3f, 3g, 3h, 3i, 3j, 6a, 6f, and 6i) were subjected to VEGFR-2 enzyme inhibitory activity testing to further explore their mechanism of action. The tested compounds showed remarkable enzyme inhibition in micromolar concentrations ranging from 0.07 to 0.36 μM, compared with Sorafenib and Sunitinib with IC50 values of 0.06 and 0.12 μM, respectively. The most promising candidate, 3j, was further evaluated for its cell cycle phases, apoptotic induction ability, as well as its antiproliferative activity and inhibitory potential for endothelial cell migration, analyzed by a cell scratch assay. Furthermore, in silico studies were also performed to identify and detect the stability of the binding poses.
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    The potential of Genus Rumex as a valuable source of health-promoting metabolites: A review of ethnomedicinal and pharmacological uses in the treatment of skin diseases
    (NIDOC (Nat.Inform.Document.Centre), 2024-08) Ezzat, Shahira; El Hawary, Seham; kirollos, farid; Gohar, Mai
    Skin diseases display essential disorders that threaten human health worldwide thus, there is an urge to find effective remedies for treating such diseases, especially from natural products which can be safer, more available, and cheaper than synthetic drugs. Rumex is one of the interesting drugs known to have a beneficial curing effect on various skin disorders especially through exerting antiaging and depigmentation activities. Genus Rumex is the second largest genus in the Polygonaceae family which consists of almost 200 species that are rich in various bioactive compounds such as flavonoids, anthraquinones, chromones, and stilbenes. The presence of numerous classes of bioactive constituents in Rumex was reflected in its pharmacological activities, thus the plant has potential anti-cancer, anti-diabetic, anti-inflammatory, and anti-oxidant effects together with its antiaging, anti-wrinkes and skin depigmentation. In this review, we provided an overview of the active compounds of Genus Rumex as well as its biological activity with a special emphasis on its effect on skin diseases.
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    Reverse pharmacology and drug repositioning in drug discovery
    (Elsevier, 2024-01) Salem, Mohamed A; Salama, Maha M; Ezzat, Shahira M
    Drug discovery is a tedious process that takes a long time and high cost, while reverse pharmacology is a target-based procedure, which depends mainly on identifying the molecular target. Reverse Pharmacology is a paradigm shift that augments the collaboration between modern advanced sciences with traditional medicine and modern biomedicine to provide better and safer leads, it is an approach that deals with transferring documented observational achievement into successful models. For this reason, reverse pharmacology is now a tool for drug discovery from synthetic and natural products. Drug repositioning is the new use for an old approved drug, that may be marketed for the treatment of certain diseases. Drug repositioning can be a tool for drug discovery that can save time and money if it is based on reliable clinical observations which are then combined with the computational tools in order to obtain the required results at an appropriate time. In this chapter, we will have an overview of the concepts of reverse pharmacology and drug repositioning and their applications in drug discovery.
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    Vortioxetine ameliorates experimental autoimmune encephalomyelitis model of multiple sclerosis in mice via activation of PI3K/Akt/CREB/BDNF cascade and modulation of serotonergic pathway signaling
    (Elsevier B.V., 2024-08) Shafiek, Marwa S; Mekky, Radwa Y; Nassar, Noha N; El-Yamany, Mohammed F; Rabie, Mostafa A
    Multiple sclerosis (MS) is a chronic condition characterized by immune cell infiltration and cytokine overproduction that led to myelin sheath inflammatory assaults, thus causing axonal destruction. The former consequently provokes motor impairment and psychological disorders. Markedly, depression is one of the most prevalent lifelong comorbidities that negatively impacts the quality of life in MS patients. Vortioxetine (VTX), a multi-modal molecule prescribed to manage depression and anxiety disorder, additionally, it displays a promising neuroprotective properties against neurodegenerative diseases such as Alzheimer's and Parkinson's. To this end, the present study investigated the potential therapeutic efficacy of VTX against experimental autoimmune encephalomyelitis (EAE) model of MS in mice. Notably, treatment with VTX significantly ameliorated EAE-induced motor disability, as evident by enhanced performance in open field, rotarod and grip strength tests, alongside a reduction in immobility time during the forced swimming test, indicating a mitigation of the depressive-like behavior; outcomes that were corroborated with histological examinations and biochemical analyses. Mechanistically, VTX enhanced serotonin levels by inhibiting both serotonin transporter (SERT) and indoleamine 2,3-dioxygenase (IDO) enzyme, thereby promoting the activation of serotonin 1A (5-HT1A) receptor. The latter triggered the stimulation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) cascade that entailed activation/phosphorylation of cAMP response element-binding protein (CREB). This activation increased brain derived neurotrophic factor (BDNF) and myelin basic protein (MBP) contents that mitigated demyelination in the corpus callosum. Furthermore, VTX suppressed phospho serine 536 nuclear factor kappa B (pS536 NF-κB p65) activity and reduced tumor necrosis factor-alpha (TNF-α) production. The results underscore VTX's beneficial effects on disease severity in EAE model of MS in mice by amending both inflammatory and neurodegenerative components of MS progression.
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    Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024-08) Agiba, Ahmed M; Elsayyad, Nihal; ElShagea, Hala N; Metwalli, Mahmoud A; Mahmoudsalehi, Amin Orash; Beigi-Boroujeni, Saeed; Lozano, Omar; Aguirre-Soto, Alan; Arreola-Ramirez, Jose Luis; Segura-Medina, Patricia; Hamed, Raghda Rabe
    Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.
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    Panicum maximum Jacq. mediated green synthesis of silver nanoparticles: synthesis, characterization, and biological activities supported by molecular docking
    (Taylor and Francis Ltd, 2024-08) Alhamdi, Heba W; Anazi, Hanan Khalaf; Mokhtar, Fatma Alzahraa; Elhawary, Seham S; Elbehairi, Serag Eldin I; Alfaifi, Mohammad Y; Shati, Ali A; Fahmy, Lamiaa I; Elekhnawy, Engy; Hassan, Afnan; Negm, Walaa A; Fahmy, Sherif Ashraf; Selim, Nabil
    This study uses the aerial parts of Panicum maximum total extract (PMTE) to synthesize silver nanoparticles (AgNPs) in an environmentally friendly manner. TEM, SEM, FTIR, X-ray powder diffraction (XRD), Zeta potential, UV, and FTIR were used to characterize the green silver nanoparticles (PM-AgNPs). PM-AgNPs were evaluated as anticancer agents compared to (PMTE) against breast (MCF-7), lung (A549), and ovary adenocarcinoma (SKOV3) human tumour cells. The antibacterial activity of AgNPs was assessed against Staphylococcus aureus isolates. The PM-AgNPs had an absorbance of 418 nm, particle size of 15.18 nm, and zeta potential of −22.4 mV, ensuring the nanosilver’s stability. XRD evaluated the crystallography nature of the formed PM-AgNPs. The cytotoxic properties of PM-AgNPs on MCF-7 and SKOV 3 were the strongest, with IC50s of 0.13 ± 0.015 and 3.5 ± 0.5 g/ml, respectively, as compared to A549 (13 ± 3.2 µg/mL). The increase in the apoptotic cells was 97.79 ± 1.61 and 96.6 ± 1.91% for MCF-7 and SKOV3 cell lines, respectively. PM-AgNPs were found to affect the membrane integrity and membrane permeability of 50 and 43.75% of the tested isolates, respectively. Also, PM-AgNPs have recorded a reduction in the biofilm formation of S. aurues. These results suggest using PM-AgNPs to treat breast and ovarian cancers.
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    Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024-07) Abdelmonem, Basma Hossam; Abdelaal, Noha M; Anwer, Eman K. E; Rashwan, Alaa A; Hussein, Mohamed Ali; Ahmed, Yasmin F; Khashana, Rana; Hanna, Mireille M; Abdelnaser, Anwar
    Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.