Browsing by Author "Othman, Mohamed S"

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Allicin mitigates hepatic injury following cyclophosphamide administration via activation of Nrf2/ARE pathways and through inhibition of inflammatory and apoptotic machinery
(Springer, 3/24/2021) Sun, Dongsheng; Sun, Chen; Qiu, Gongcai; Yao, Lei; Yu, Jian; Al Sberi, Hassan; Fouda, Manar S; Othman, Mohamed S; Lokman, Maha S; Kassab, Rami B; Abdel Moneim, Ahmed E
Treatment with anti-neoplastic agents, including cyclophosphamide (CP), is associated with several adverse reactions. Here, we distinguished the potential protective effect of allicin against CP-mediated hepatotoxicity in rats. To assess the effect of allicin, four experimental groups were used, with 7 rats per group, including control, allicin (10 mg/kg), CP (200 mg/kg), and allicin + CP-treated groups. All groups were treated for 10 days. Blood and liver samples were collected for biochemical, molecular, and histological analyses. Treatment with CP led to deformations in the liver tissue that were associated with higher liver function markers (alanine transaminase, aspartate transaminase, and alkaline phosphatase). Additionally, a disturbance in the redox balance was observed after CP exposure, as indicated by increased levels of oxidants, including malondialdehyde and nitric oxide, and the decreased levels of endogenous antioxidants, including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. At the molecular level, CP treatment resulted in reduced expression of the Nrf2/ARE pathway and other genes related to this pathway, including NAD(P)H quinone dehydrogenase 1 and glutamate-cysteine ligase catalytic subunit. CP also led to a hyper-inflammatory response in hepatic tissue, with increased production of pro-inflammatory cytokines, including tumor necrosis factor-alpha and interlukin-1beta, and upregulation of nitric oxide synthase 2. CP also enhanced the immunoreactivity of the profibrogenic cytokine, transforming growth factor-beta, in liver tissue. Upregulation of caspase 3 and Bcl-2-associated X protein and downregulation of B-cell lymphoma 2 were also observed in response to CP treatment. Treatment with allicin reversed the molecular, biochemical, and histological changes that occurred with CP exposure. These results suggest that allicin can be used in combination with CP to avoid hepatotoxicity.
Antitumor Activity of Zinc Nanoparticles Synthesized with Berberine on Human Epithelial Colorectal Adenocarcinoma (Caco-2) Cells through Acting on Cox-2/NF-kB and p53 Pathways
(Bentham Science Publishers B.V., 2022-06) Othman, Mohamed S; Al-Bagawi, Amal H; Obeidat, Sofian T; Fareid, Mohamed A; Habotta, Ola A; Abdel Moneim, Ahmed E
Background: Drawbacks and side effects of currently available therapies to colorectal cancer (CRC) have compelled researchers to search for new therapeutic strategies. Objective: This study was designed to investigate the effects of zinc nanoparticles biosynthesized with berberine (ZnNPs-BER) on Caco-2 cells compared to 5-Fluorouracil (5-FU) and explore the possible underlying pathways. Methods: Caco-2 and Vero cells were treated with 5-FU, BER, or ZnNPs-BER for 24 h. Cell viability was measured by MTT assay. Oxidative stress and apoptotic markers and cell cycle were determined. Additionally, Cox-2 and NF-kB levels were also measured. Results: The IC50 values of 5-FU, BER, and ZnNPs-BER on Caco-2 cells were found to be 34.65 µM, 19.86 µg/ml and 10.49 µg/ml, respectively by MTT assay. The IC50 value for 5-FU in Vero cells was 21.7 μg/ml, however, BER and BER-ZnNPs treatment showed non-toxic effects on the Vero cells. Further, ZnNPs-BER exerted significant induction of ROS besides exhaustion of the antioxidant capacity of tumor cells indicated by a decline in GSH and elevated NO and MDA contents. Marked increments in levels of Bax and caspase-3 were detected together with declines in Bcl-2 levels in Caco-2 cells subjected to BER-ZnNPs therapy. On the molecular basis, upregulation in mRNA levels of pro-apoptotic genes (Bax, caspase-3, and tumor suppressor gene p53) along with downregulation in the anti-apoptotic gene (Bcl-2) were observed in ZnNPs-BER treated Caco-2 cells. Furthermore, ZnNPs-BER showed more pronounced effects on apoptosis increased cell percentage in the S and subG1 phases. In addition, green synthesis of ZnNPs with BER showed notable induction of Cox2 and NF-kB in Caco-2 cells. Conclusion: Therefore, the antitumor potential of ZnNPs-BER in colon cancer cells may be endorsed for induction of oxidative stress, inflammation, and apoptotic changes in tumor cells. Our study documents the therapeutic potential of Zn nanoparticles conjugated with BER, which may be a new option for combined chemotherapy. © 2022 Bentham Science Publishers
Design, synthesis, in vitro urease inhibitory potentials and in silico molecular docking study of benzimidazole bearing thiosemicarbazides/ sulfonamide Analogues
(Elsevier, 2023-10) Alzahrani, Abdullah Yahya Abdullah; Adalat, Bushra; Ullah, Hayat; Taha, Muhammad; Othman, Mohamed S; Fareid, Mohamed A; Khaled, Azza M; Rahim, Fazal
The nickel-containing urease enzyme is responsible for the pathogenesis of hepatic coma, hepatic encephalop- athy, urolithiasis, gastric and peptic ulcer. These enzymes also have a negative effect on the efficacy of soil nitrogen to produce crops. The urease enzyme inhibitors may be thought as a strategy for reducing the negative effects of ureolytic bacteria. The present study involves a novel approach to the synthesis benzimidazole thio- semicarbazides and sulphonamide derivatives as potent urease inhibitor. All the analogues exhibited good in- hibition potential. Among the thiosemicarbazides series, the most potent were analogs 1 g and 1 h having an IC50 = 2.40 ± 0.10 and 3.10 ± 0.10 µM respectively. Among the sulphonamide series, the most potent analogs were 2f and 2j having an IC50 = 3.90 ± 0.10 and 1.40 ± 0.001 µM respectively. Structure activity relationship study shows that among the two series, the most potent analogs were those having electron-withdrawing groups. Molecular docking study was carried out to check the interactions between the synthesized compounds and the urease enzyme’s active sites. Furthermore, to evaluate the stability of the most active compound in complex with the urease enzyme a total of 200 ns MD simulation was carried out. The MD simulation study revealed that the compound formed a more stable complex with the urease enzyme and remained stable throughout the 200 ns MD simulation. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.
Evaluation of the Potential Role of Silver Nanoparticles Loaded with Berberine in Improving Anti-Tumor Efficiency
(Tumos. Press, 2022-03) Othman, Mohamed S; Obeidat, Sofian T; Al-Bagawi, Amal H; Fareid, Mohamed A; El-Borady, Ola M; Kassab, Rami B; Abdel Moneim, Ahmed E
Background: Cancer is a progressive disease, its incidence and death rates are rapidly increasing globally. Numerous adverse effects are associated with the available interventions. Hence, the current study was undertaken to explore the anticancer effect of silver nanoparticles conjugated with berberine (AgNPs-BER) against Ehrlich solid carcinoma (ESC) in mice. Methods: Male Swiss albino mice were allocated randomly into ESC, ESC+cisplatin (CP; 5 mg/ kg), ESC+AgNPs-BER (20 mg/kg), and ESC+cisplatin and AgNPs-BER groups. Results: AgNPs-BER administration increased significantly the survival rate and decreased body weight and tumor size as compared to ESC group. Additionally, AgNPs-BER enhanced the development of oxidative stress in the tumor tissue as indicated by the increased lipid peroxidation (LPO) and nitric oxide (NO) accompanied by a decrease in the examined antioxidant proteins (glutathione (GSH) and its derived enzymes along with superoxide dismutase and catalase). AgNPs-BER was found also to trigger apoptotic cascade in the tumor cells through upregulating the mRNA expression of the pro-apoptotic proteins (Bax and caspase-3) and downregulating the mRNA expression of the anti-apoptotic protein (Bcl-2). Moreover, AgNPs-BER improved partially the histopathological alterations in the developed tumor tissue as compared to ESC group. Conclusion: Collectively, AgNPs-BER could be applied as an antitumor agent due to its pro- oxidant, pro-apoptotic, and antiangiogenic effects.
Green Synthetized Selenium Nanoparticles Using Syzygium aromaticum (Clove) Extract Reduce Pentylenetetrazol-Induced Epilepsy and Associated Cortical Damage in Rats
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-01) Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Al-Bagawi, Amal H; Fareid, Mohamed A; Abdel Hameed, Reda; Mohamed, Kareem M; Abdelfattah, Mohamed S; Fehaid, Alaa; Hussein, Manal M; Aboelnaga, Shimaa M. H; Abdel Moneim, Ahmed E
We aimed to investigate the potential anticonvulsant effect of green synthetized sele- nium nanoparticles (SeNPs) using Syzygium aromaticum extract (SAE) (SAE-SeNPs) against epileptic seizures and cortical damage induced by pentylenetetrazole (PTZ) injection in rats and its mechanism. A total of 84 rats were divided into six groups; control, PTZ-exposed group, SAE + PTZ-treated group, sodium selenite (Na2SeO3 ) + PTZ-treated group, SAE-SeNPs + PTZ-treated group, and diazepam + PTZ-treated group. SAE-SeNPs significantly increase (p < 0.05) the latency time to seizures and reduce both the seizure duration and death rate, which were enhanced by the PTZ injection. SAE-SeNPs counteracted the PTZ-induced changes in the oxidants and antioxidants. Furthermore, SAE-SeNPs significantly restored (p < 0.05) the pro-inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) to their normal levels and suppressed the activity of the glial fibrillary acidic protein showing their inhibitory effect on the epilepsy-associated inflammation. In addition, SAE-SeNPs significantly reduced (p < 0.05) PTZ-induced cortical cell apoptosis, as revealed by a reduction in the pro-apoptotic Bax and caspase-3 levels, and an elevation of the anti-apoptotic Bcl-2 level. Moreover, SAE-SeNPs significantly modulate (p < 0.05) the PTZ-induced changes in the neuro- transmitter norepinephrine level and acetylcholinesterase enzymatic activity. These data concluded the anticonvulsant activity of SAE-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their ability to modulate neurotransmitters.
Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2)
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-02) Khaled, Azza M; Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Aboelnaga, Shimaa M; Fehaid, Alaa; Hathout, Heba M. R; Bakkar, Ashraf A; Abdel Moneim, Ahmed E; El-Garawani, Islam M; Morsi, Dalia S
A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers’ (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.
Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent
(Elsevier, 07/11/2021) Othman, Mohamed S; Obeidat, Sofian T; Al-Bagawi, Amal H; Fareid, Mohamed A; Fehaid, Alaa; Abdel Moneim, Ahmed E
Objective The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs). Methods SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na2SeO3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin (5 mg/kg), EST + Ber (20 mg/kg), and EST+ SeNPs-Ber (0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size, gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates. Results Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by upregulating the Bcl-2-associated X protein and caspase-3 expression rates and downregulating the B-cell lymphoma 2 expression rate. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group. Conclusion Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.
Hepatorenal protective efficacy of flavonoids from Ocimum basilicum extract in diabetic albino rats: A focus on hypoglycemic, antioxidant, anti-inflammatory and anti-apoptotic activities
(Elsevier, 2021-12) Othman, Mohamed S; Khaled, Azza M; Al-Bagawi, Amal H; Fareid, Mohamed A; Ghany, Reda A; Habotta, Ola A; Abdel Moneim, Ahmed E
Plant derived phytochemical therapy is a bright candidate for treatment of diabetes and its associated complications. Ocimum baslicum is used as an anti-diabetic traditional medicine. Hence, the present study investigated the effect of Hail Ocimum extract (HOE) and its total flavonoids (HOETF) against hepatorenal damage in experimental diabetes induced by high-fat diet (HFD) and injection of streptozotocin (STZ) in rats. Diabetic animals were co-treated daily with HOE, HOETF or metformin (MET) as a standard anti-diabetic drug for four weeks. Compared to controls, HFD/STZ-treatment lead to significant increases in fasting blood glucose, insulin and HOMA-IR levels. Furthermore, diabetic rats had elevated hepatic (ALT and ALP) and kidney functions (urea and creatinine) biomarkers together with disturbed lipid profile and decreased PPAR-γ gene expression. Higher levels of hepatic and renal LPO and NO paralleled with lower levels of GSH and activities of antioxidant enzymes (SOD, CAT, GPx and GR) after HFD/STZ treatment. Additionally, noteworthy inflammatory and apoptotic responses were evident in both organs of diabetic rats as witnessed by augmented levels of TNF-α, IL-1b and Bax levels with declined levels of Bcl-2. Moreover, histological examination of hepatic, renal and pancreatic tissues validated the biochemical findings. On contrary, co-treatment of diabetic animals with HOE or HOETF could decrease glucose and insulin levels together with improvement of lipid markers and alleviation of hepatorenal dysfunction, oxidative injury, inflammatory and apoptotic events. Conclusively, HOE or HOETF could be a promising complementary therapeutic option for the management of diabetic hepatorenal complication owing to their antioxidant, anti-inflammatory; anti-apoptotic properties.
Investigation of novel benzimidazole-based indole/thiazole hybrids derivatives as effective anti-diabetics and anti-alzheimer’s agents: Structure-activity relationship insight, in vitro and in silico approaches
(Elsevier B.V., 2024-05) Naz, Haseena; Othman, Mohamed S; Rahim, Fazal; Hussain, Rafaqat; Khan, Shoaib; Taha, Muhammad; Hafez, Mohamed M; Abdel-Hafez, Lina JM; Ullah, Hayat; Khan, Ihsan Ullah; Khan, Yousaf; Shah, Syed Adnan Ali
Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are common in developed countries and their incidence is increasing. The research is mostly concentrated on the exploration of novel therapies to remedy or avert these ailments. AD and T2DM have several molecular pathways in common that contributes to their degenerative development. A novel series of ten hybrid analogues (1–10) based on benzimidazole bearing indole analogues were synthesized and these scaffolds were characterized by spectroscopic techniques like HR-EIMS, 13CNMR and 1 HNMR. Furthermore, the synthesized moieties were screened for α-amylase and α-glucosidase inhibitory activities. All these synthesized analogues showed good to moderate α-amylase and α-glucosidase inhibition potency ranging (4.90 ± 0.10 to 15.30 ± 0.60 µM) and (5.30 ± 0.10 to 16.10 ± 0.60 µM) while acarbose was used as a reference standard (IC50 = 10 0.30 ± 0.20 µM), (IC50 = 9.80 ± 0.20 µM). Another series of ten hybrid analogues (11–20) based on benzimidazole bearing thiazole moieties were synthesized and were evaluated for AChE and BuChE inhibition activities. All these newly afforded analogues showed good to moderate AChE and BuChE inhibitory potential ranging of (IC50 = 0.20 ± 0.01 µM), (IC50 = 0.15 ± 0.01 µM) to (IC50 = 3.90 ± 0.20 µM), (IC50 = 3.80 ± 0.10 µM) while Donepezil was taken as a reference standard with (IC50 = 0.016 ± 0.01 µM), (IC50 = 0.30 ± 0.010 µM).The scaffolds were also characterized using spectroscopic techniques such as HR-EIMS, 13CNMR and 1 HNMR for a better understanding of their structure. SAR was done for all synthesized analogues for substituents.In addition, docking research was conducted to determine the binding mode of interaction between the active site of analogues and targeted enzymes. This work aims to estimate the potential of the synthesized scaffolds as competitors to existing drugs. Incorporating molecular docking analysis with in vitro activities improves the accuracy of predictions and validates the possibility of these compounds as options for treating type-2 diabetes and Alzheimer’s disease.
Narrowband Near-Infrared Perovskite/Organic Photodetector: TCAD Numerical Simulation
(Multidisciplinary Digital Publishing Institute (MDPI), 2022-07) Salem, Marwa S; Shaker, Ahmed; Al-Bagawia, Amal H; Aleid, Ghada Mohamed; Othman, Mohamed S; Alshammari, Mohammad T; Fedawy, Mostafa
Narrowband photodetectors (PD) established in the near-infrared (NIR) wavelength range are highly required in a variety of applications including high-quality bioimaging. In this simulation study, we propose a filter-less narrowband PD based on the architecture of perovskite/organic het- erojunction. The most decisive part of the photodetector is the hierarchical configuration of a larger bandgap perovskite material with a thicker film followed by a lower bandgap organic material with a narrower layer. The design of the structure is carried out by TCAD numerical simulations. Our structure is based on an experimentally validated wideband organic PD, which is modified by invok- ing an additional perovskite layer having a tunable bandgap. The main detector device comprises of ITO/perovskite (CsyFA1−yPb(IxBr1−x)3 )/organic blend (PBDTTT-c:C60-PCBM)/PEDOT:PSS/Al. The simulation results show that the proposed heterojunction PD achieves satisfactory performance when the thickness of perovskite and organic layers are 2.5 µm and 500 nm, respectively. The designed photodetector achieves a narrow spectral response at 730 nm with a full width at half-maximum (FWHM) of 33 nm in the detector, while having a responsivity of about 0.12 A/W at zero bias. The presented heterojunction perovskite/organic PD can efficiently detect light in the wavelength range of 700 to 900 nm. These simulation results can be employed to drive the development of filter-less narrowband NIR heterojunction PD.
New Cholinesterase inhibitors based on 1,2,4-triazole bearing benzenesulfonohydrazide skeleton: Synthesis, in vitro and in silico studies
(Elsevier B.V, 2024-08) Othman, Mohamed S; Naz, Haseena; Rahim, Fazal; Ullah, Hayat; Hussain, Rafaqat; Taha, Muhammad; Khan, Shoaib; Fareid, Mohamed A; Aboelnaga, Shimaa M; Altaleb, Anas T; Iqbal, Rashid; Shah, Syed Adnan Ali
We have synthesized 1,2,4-triazole bearing benzenesulfonohydrazide analogues (1–21), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and were evaluated against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes. All the newly synthesized analogues showed excellent to good inhibition potential with IC50 values ranged from 0.30 ± 0.050 to 15.21 ± 0.50 µM (against AChE) and 0.70 ± 0.050 to 18.27 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Analogues 2 and 4 which were found inactive against these enzymes. However, analogues 17 (IC50 = 0.30 ± 0.050 and 0.70 ± 0.050 µM) and 13 (IC50 = 0.70 ± 0.05 and 1.70 ± 0.050 µM) were found to have potent inhibitory potentials against the targeted enzymes. Structure-activity relationship was carried out which mainly depends upon the nature, position and numbers of the substitution present on phenyl rings that may be electron withdrawing/donating. Molecular docking study was carried out to know about the binding mode of interaction of the most active site of the synthesized analogues with the targeted enzymes.
Numerical analysis and design of high performance HTL-free antimony sulfide solar cells by SCAPS-1D
(Elsevier, 07/12/2021) Salem, Marwa S; Shaker, Ahmed; Othman, Mohamed S; Al-Bagawia, Amal H; Fedawy, Mostafa; Aleid, Ghada Mohamed
Among the various absorbers encountered in thin film solar cells (TFSCs), antimony sulfide (Sb2S3) is considered a suitable candidate as it is a non-toxic and earth-abundant besides its high absorption coefficient. However, some critical issues cause its poor photovoltaic performance. These include unoptimized Sb2S3 layer, interface recombination and cell properties like the ineffective carrier collection and transport. To enhance the power conversion efficiency (PCE) of Sb2S3 solar cell, we suggest some design guidelines by employing device simulation. First, a calibration step is performed vs an experimental arrangement consists of FTO/TiO2/Sb2S3/Spiro-OMeTAD/Au to validate the simulation model. Next, as the organic hole transport material (HTM) often has poor long-term operation stability and demands high-cost fabrication processes, an HTL-free cell is proposed and designed by investigating the impact of the main technological and physical parameters. In the first step in the design of the HTL-free cell, we provide an affinity engineering methodology to tune the conduction band offset between the electron transport layer (ETL) and the absorber. Based on this approach, the most appropriate electron transport material (ETM) is chosen that fulfills the maximum efficiency. Then, an optimization routine is performed to select the most appropriate design parameters and the PCE of the optimized case is found to be about 22%. All simulations, carried out in this work, are performed by SCAPS-1D device simulator under AM1.5G illumination and 300 K temperature.
Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain
(Walter de Gruyter GmbH, 2022-11) Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Abdel-Daim, Mohamed M; Habotta, Ola A; Schwartz, Laurent; Al-Bagawi, Amal H; Hussein, Manal M; Bakkar, Ashraf
In this study, the nepuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)- induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally with PbAc (20 mg/kg) for 2 weeks. Notably, SeNPs-PtE decreased brain Pb accumulation and enhanced the level of dopamine and the activity of AChE compared to the control rats. In addition, elevated neural levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione along with decreased lipid peroxidation levels were noticed in pretreated groups with SeNPs-PtE. Moreover, SeNPs-PtE significantly sup- pressed neural inflammation, as indicated by lower levels of interleukin-1 beta, interleukin-6, tumor necrosis factor- alpha, nuclear factor-kappa B p65, and nitric oxide in the examined brain tissue. The molecular results also unveiled significant down-regulation in iNOS gene expression in the brains of SeNPs-PtE-treated rats. In addition, SeNPs- PtE administration counteracted the neural loss by increasing B-cell lymphoma 2 (Bcl-2) and brain-derived neurotrophic factor levels as well as decreasing BCL2-associated X protein and caspase-3 levels. To sum up, our data suggest that P. tomentosa extract alone or in combination with SeNPs has great potential in reversing the neural tissue impairment induced by PbAc via its antioxidant, anti-inflammatory, and anti-apoptotic activities. This study might have therapeutic implications in preventing and treating several lead-induced neurological disorders.
The Potential Protective Effect of Orange Peel and Selenium against 17β-Estradiol-Induced Chronic Non-Bacterial Prostatitis in Rats
(Bentham Science Publishers, 2020-03) Almeer, Rafa S.; Muhammad, Nada A.E.; Othman, Mohamed S; Aref, Ahmed M; Elgamal, Basma; Abdel Moneim, Ahmed E
Background: Prostate Cancer (PCa) is defined as a major health problem facing the male population. Aims: We aimed to investigate the protective effects of Orange Peel Extract (OPE) and/or selenium (Se) on chronic non-bacterial prostatitis in a rat model. Methods: Fifty-six adult male Wistar albino rats were castrated; after 5 days, they were divided randomly into eight groups (n= 7). The control group received saline treatment; while 17β-estradiol (E2) (0.25mg/kg) was injected subcutaneously in rats from Groups V, VI, VII, and VIII to induce chronic non-bacterial prostatitis. They were then treated with OPE (400mg/kg body weight; Groups II, IV, VI, and VIII) and/or sodium selenite (0.5mg/kg body weight; Groups III, IV, VII, and VIII) for 30 days. Interleukin-2 (IL2) and Prostate Cancer Antigen 3 (PCA3) mRNA expressions were determined using qPCR; Prostate-Specific Antigen (PSA) protein expression was determined immunohistochemically. Prostate tissue histology was examined by hematoxylin and eosin staining, and the levels of oxidative stress markers and antioxidant enzymes were measured. Results: E2 administration significantly increased IL2 and PCA3 mRNA expressions, and PSA protein expression. It also increased the prostate wet weight and body weight, and lipid peroxidation, nitric oxide, TNF-α, and IL-1β levels, decreased the glutathione and antioxidant enzyme levels, and caused distinct histological alterations in the prostate gland. OPE and/or Se markedly improved all the studied parameters due to their antioxidant properties and anti-inflammatory effects. Conclusion: OPE and Se showed protective effects against 17β-estradiol-induced chronic nonbacterial prostatitis. These results suggest that protection of chronic non-bacterial prostatitis by OPE+Se combination involves anti-oxidation, and anti-inflammation. Moreover, their synergistic mechanism was mostly achieved via the regulation of oxidative stress and inflammation processes
The Potential Therapeutic Role of Green-Synthesized Selenium Nanoparticles Using Carvacrol in Human Breast Cancer MCF-7 Cells
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-06) Othman, Mohamed S; Aboelnaga, Shimaa M; Habotta, Ola A; Abdel Moneim, Ahmed Email; Hussein, Manal M
The disadvantages and side effects of currently available breast cancer (BC) therapies have compelled researchers to seek new therapeutic strategies. This study was designed to investigate the effect of selenium nanoparticles biosynthesized with carvacrol (SeNPs-CV) on breast cancer (MCF-7) cell lines and to explore possible underlying pathways. Flow cytometry, MTT assays, and various biochemical techniques were used to evaluate the anti-proliferative effects of SeNPs-CV on MCF-7 cells. Cytotoxicity assays showed that treatment with SeNPs-CV could effectively reduce MCF-7 cell proliferation and viability in a dose-dependent manner. However, SeNPs-CV had no cytotoxic effect against Vero cells. Furthermore, SeNPs-CV showed better anticancer activity than metal nanoparticles of selenium evidenced by the lower IC50 obtained in MCF-7 cells (8.3 µg/mL versus 41.6 µg/mL, respectively). Treatment with SeNPs-CV directly targeted Bcl-2, Bax, and caspase-3, leading to the mitochondrial leakage of cytochrome C and subsequent activation of the apoptotic cascade in MCF-7 cells. In addition, MCF-7 cells treated with SeNPs-CV exhibited elevated levels of oxidative stress, as indicated by noticeable rises in 8-OHDG, ROS, NO, and LPO, paralleled by significant exhaustion in GSH levels and antioxidant enzymes activity. In addition, the administration of SeNPs-CV induced the inflammatory mediator IL-1β and downregulated the expression of cell-proliferating nuclear antigen (PCNA) in MCF-7 cells, which plays a critical role in apoptosis. Therefore, the ability of SeNPs-CV to fight BC may be due to its ability to induce oxidative stress, inflammation, and apoptosis in tumor cells. These findings demonstrate the therapeutic potential of Se nanoparticles conjugated with CV, which may provide a novel approach for combination chemotherapy in BC.
Protective effect of Allium atroviolaceum-synthesized SeNPs on aluminum-induced brain damage in mice
(Walter de Gruyter GmbH, 2022-11) Othman, Mohamed S; Obeidat, Sofian T; Aleid, Ghada M; Al-Bagawi, Amal H; Fehaid, Alaa; Habotta, Ola A; Badawy, Mohamed M; Elganzoury, Sara S; Abdalla, Mohga S; Abdelfattah, Mohamed S; Daiam, Mohamed A; Abdel Moneim, Ahmed E
reduction in AChE as compared with the AlCl3 group. Therefore, our results indicate that SeNPs-AaE has a potential neuroprotective effect against Al-mediated neurotoxic effects because of its powerful antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.
Synthesis, in vitro biological evaluation and in silico molecular docking study of hydroxy‑quinoline based sulfonohydrazide derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors
(Elsevier, 2024-02) Alzahrani, Abdullah Yahya Abdullah; Ullah, Hayat; Rahim, Fazal; Khan, Fahad; Wadood, Abdul; Taha, Muhammad; Al-Bagawi, Amal; Fareid, Mohamed; Othman, Mohamed S
A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1 HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes.