Browsing by Author "Obeidat, Sofian T"

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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
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.
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.
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.