Browsing by Author "Fareid, Mohamed A"

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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-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.
New benzimidazole based Schiff bases as potent anti-alzheimer agents: Synthesis, bio-evaluation and molecular docking study
(Elsevier, 2024-03) Othman, Mohamed s; Hayat, Shawkat; Rahim, Fazal; Taha, Muhammad; Sajid, Muhammad; Khan, Shoaib; Iqbal, Wajeeha; Shah, Syed Adnan Ali; Fareid, Mohamed A; Aboelnaga, Shimaa M; Abdel-Hafez, Lina JM; Hafez, Mohamed M
In search of potent anti-Alzheimer agent benzimidazole based Schiff base derivatives (1–18) were synthesized and evaluated as dual inhibitor for acetylcholinesterase and butyrylcholinesterase enzymes. All analogs among the series except analog 1 and 16 showed a variable degree of inhibitory activity with IC50 value ranging between 0.10 ± 0.01 to 12.40 ± 0.30 µM for acetylcholinesterase and 0.20 ± 0.01 to 11.10 ± 0.30 µM for butyrylcholinesterase. The most potent analog found among the series was analog 8 having IC50 value 0.10 ± 0.01 and 0.20 ± 0.01 µM for both acetylcholinesterase and butyrylcholinesterase inhibition respectively. The structures of all synthesized analogs were confirmed through NMR and HR-EIMS. Structure activity relationship (SAR) has been established for all newly synthesized derivatives. To understand the binding interaction of most active derivatives with enzyme active site, molecular docking study were performed. The toxicity and mutagenicity of compound 8 was predicted using in silico software, namely Derek Nexus® (version 6.3). Various toxicity endpoints, including chromosomal damage, skin sensitization, hepatotoxicity were predicted. The degradation profile of compound 8 was predicted in silico by Zeneth software (version 9.0.1) resulting in a probability of the formation of seven potential degradation products.
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.