Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity

Ghareeb Doaa A.,Saleh Samar R.,Seadawy Mohamed G.,Nofal Mohammed S.,Abdulmalek Shaymaa A.,Hassan Salma. F.,Khedr Shaimaa M.,AbdElwahab Miral G.,Sobhy Ahmed A.,Abdel-Hamid Ali saber Ali,Yassin Abdelrah 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.6

Purpose A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl- 1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.

Potential therapeutic and pharmacological strategies for SARS-CoV2

Ghareeb Doaa A.,Saleh Samar R.,Nofal Mohammed S.,Kaddah Mohamed M. Y.,Hassan Salma. F.,Seif Inas K.,El-Zahaby Sally A.,Khedr Shaimaa M.,Kenawy Marwa Y.,Masoud Aliaa A.,Soudi Salma A.,Sobhy Ahmed A.,Se 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.3

Background At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic. Area covered Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARSCoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti- SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2. Expert opinion A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate.

A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats

Ghada Nady Ouais,Doaa Mohamad Hassan 대한해부학회 2023 Anatomy & Cell Biology Vol.56 No.4

Exposure to environmental pollutants such as carbon tetrachloride (CCL4) causes liver damage. This study aimed to compare the ameliorative activity of the dates flesh extract (DFE) and selenium-nanoparticles (SeNPs) on CCL4- induced hepatotoxicity and if DFE could be a useful alternative supplement. Twenty-four male albino rats were enrolled and randomly divided into four equal groups (6 rats in each group): control group received only basal diet with no medications. Group II received CCL4 in a dose of 0.5 mg/kg intraperitoneal injection twice weekly for four weeks. Group III rats were pretreated with SeNPs in a dose of 2.5 mg/kg once a day orally three times/wk for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. Group IV rats were pretreated with DFE in a dose of 8 ml of the aqueous extract/kg/d orally for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. The liver damage was assessed by estimation of plasma concentration of albumin and enzymes activities of alanine aminotransferase and tissue genes expression. Liver oxidation levels were assessed by measuring the tissue concentration of the malondialdehyde, superoxide dismutase, and the total glutathione. Additionally, inflammatory mediators tumour necrosis factor--α and interleukin-6 were estimated. Detecting the liver’s cellular structural damage was done by histopathological and immunohistochemical examination. This study suggests that CCL4-induced liver damage in rats can be protected by administration whether the costly SeNPs or the economical DFE.

Peritoneal cancer index as a predictor of survival in advanced stage serous epithelial ovarian cancer: a prospective study

Alaa A. Elzarkaa,Waleed Shaalan,Doaa Elemam,Hassan Mansour,Mahmoud Melis,Eduard Malik,Amr A. Soliman 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.4

OBJECTIVE: A numerical score, the peritoneal cancer index (PCI), was developed to reflect the extent of tumor growth in gastric and colorectal cancers and to tailor treatment. This study aimed to examine the value of the PCI score in advanced epithelial ovarian cancer (EOC) regarding completeness of surgical cytoreduction and survival. METHODS: This was a prospective observational cohort study. Patients with primary serous EOC at International Federation of Gynecology and Obstetrics (FIGO) stages IIIB or higher were included. Patients with FIGO stage IVB as well as those assigned to receive neoadjuvant treatment were excluded from the study. The PCI was obtained and registered intraoperatively. RESULTS: In the study period we recruited 96 patients with serous EOC stage IIIB-IVA. A PCI score cut-off value of 13 was calculated using a receiver operator characteristic (ROC) curve, above which worse survival is expected (area under the curve [AUC]=0.641; 95% confidence interval [CI]=0.517-0.765; sensitivity and specificity 80.6%, 45.0%, respectively; p=0.050). A multivariate analysis determined that suboptimal surgical cytoreduction was the only independent predictive factor for recurrence (odds ratio [OR]=7.548; 95% CI=1.473-38.675; p=0.015). A multivariate analysis determined that only suboptimal surgical cytoreduction (hazard ratio [HR]=2.33; 95% CI=0.616-8.795; p=0.005), but not PCI score >13 (HR=1.289; 95% CI=0.329-5.046; p=0.716), was an independent predictive factor for death. CONCLUSION: We conclude from this study that the PCI score is a reliable tool helping to assess the extent of disease in advanced serous EOC patients and may help predicting complete surgical cytoreduction but cannot qualify as a predictor of survival.

Antioxidant and antibacterial activities of bioactive peptides in buffalo’s yoghurt fermented with different starter cultures

Soad Taha,Moniur El Abd,Cristian De Gobba,Mahmoud Abdel-Hamid,Ensaf Khalil,Doaa Hassan 한국식품과학회 2017 Food Science and Biotechnology Vol.26 No.5

The effect of Lactobacillus acidophilus 20552 ATCC (T2) or Lactobacillus helveticus CH 5 (T3) in combination with yoghurt starter (1:1) on the antioxidant and antibacterial activities of the bioactive peptides present in buffalo’s yoghurt was studied. The SDS-PAGE results indicate that all caseins were completely hydrolyzed by both strains, whereas whey protein fractions were still present. All starter cultures have the ability to produce lowmolecular- weight bioactive peptides, most of which were originated from b-casein and fewer from as1 casein. The antioxidant activity (%) of the water-soluble peptide extract from yoghurt samples increased in all samples during storage. Samples containing Lb. helveticus CH 5 showed the highest values. All yoghurt treatments displayed antibacterial activity against Escherichia coli. Control yoghurt and T3 showed higher antibacterial activity on E. coli, Staphylococcus aureus, and Bacillus cereus as compared to T2.