Browsing by Author "Salama, Maha M"

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Anti‑estrogenic and anti‑aromatase activities of citrus peels major compounds in breast cancer
(Nature, 2021-03) El‑Kersh, Dina M; Ezzat, Shahira M; Salama, Maha M; Mahrous, Engy A; Attia, Yasmeen M; Ahmed, Mahmoud Salama; Elmazar, Mohey M
Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of diferent varieties of citrus peels along with eight isolated favonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profle. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confrmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.
Bioactive lead compounds and molecular targets for the treatment of heart diseases
(ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, 125 LONDON WALL, LONDON EC2Y 5AS, ENGLAND, 2020) Ezzat, Shahira M; Salama, Maha M; Salem, Mohamed A.
Cardiovascular disease (CVD) is a group of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CADs) that are recognized as heart including angina attack and myocardial infarction. CVD is responsible for about 31.5% of all global deaths. About 92 million US adults suffer from CVD; this is expected to rise higher per the adult population by 2030 owing to augmentation in obesity and diabetes disorders, and consequently, healthcare services are overwhelmed with a huge load [1]. According to the World Health Organization (WHO), 2016 [2],morethan18million individuals lose their life annually from CVD and 1.1 billion adults recorded increased blood pressure. Many of these people have been exposed to unhealthy lifestyle, tobacco habits, eating foods with high salt, and deficiency in physical practice. CVDis usually accompanied by atherosclerosis and an increased risk of blood clots. Other organs, heart, kidneys, brain, and eyes, might also be damaged in response to arteries injury. Therefore, CVD is regarded as a complex disease that results from the consequence of multiple pathogenic factors, which reflects the different interactions of many interconnected genes and their relevant products [3]. Chronic proatherogenic inflammation is one of the main causes of CVDs and its supplementary severe complications. Endoplasmic reticulum (ER) is an important organelle for folding, releasing, and synthesizing secretory and transmembrane proteins. Any pathological stimuli such as hypoxia, ischemia, inflammation, and oxidative stress can change the homeostatic function of ER, and this results in the aggregation of unfolded proteins, a phenomena denoted as ER stress. This unfolded protein response, UPR (a complex signaling network), is triggered by ER stress. Massive investigations revealed that ER stress is one of the crucial phases in the progress of various CVDs such as heart failure, ischemic heart disease, and atherosclerosis. Many pharmacological therapeutics are available for treating CVDs; however, the present drugs cause many adverse effects such as renal failure, rhabdomyolysis, and hemorrhagic with prolonged use. Natural products have always been regarded as a valuable source for the discovery of new drugs [4]. Drugs or those obtained from animals, plants, or microorganisms have a great role in human healthcare. They have recorded massive diversities chemically and pharmacologically. The drugs approved by the FDA constitute more than 50% natural products or derivatives [
Comparative Metabolite Profiling of Four Polyphenol Rich Morus Leaves extracts in Relation to their Antibiofilm Activity against Enterococcus faecalis
(Hindawi, 2022-07-22) Salem, Mohamed A; Salama, Maha M; Ezzat, Shahira M; Hashem, Yomna A
Enterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilm. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm and only 4% did not form a biofilm, the strong biofilm-forming isolates were E. faecalis and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, results are in accordance with the phenolic and flavonoid content of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents.
Downregulation of MMP1 expression mediates the anti-aging activity of Citrus sinensis peel extract nanoformulation in UV induced photoaging
(Elsevier, 2021-03) Amer, Reham I; Ezzat, Shahira M; Aborehab, Nora M; Ragab, Mai F; Mohamed, Dalia; Hashad, Amira; Attia, Dalia; Salama, Maha M; El Bishbishy, Mahitab H
Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine me- tabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.
Nanotechnology in leukemia: diagnosis, efcient-targeted drug delivery, and clinical trials
(BioMed Central Ltd, 2023-11) Salama, Maha M; Aborehab, Nora M; El Mahdy, Nihal M; Zayed, Ahmed; Ezzat, Shahira M
Leukemia is a group of malignant disorders which afect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side efects and toxicity. Hence, modern research is concerned with the development of specifc nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic efects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efcient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side efects and toxicities.
Natural Products for the Management of Cardiovascular Diseases
(Bentham Science Publishers, 2020) Salem, Mohamed A; El Bishbishy, Mahitab H; Zayed, Ahmed; Mahrous, Amr A; Salama, Maha M; Ezzat, Shahira M
Cardiovascular diseases constitute a serious public health problem. It is estimated that they are responsible for nearly 30% of world mortality. Regardless of the developments in the diagnosis and management of cardiovascular diseases, their incidence rate remains increasing. Therefore, newlines of drugs are needed to manage the expanding population of patients with cardiovascular diseases. Even though the most common existing treatments for cardiovascular diseases are synthetic molecules, natural compounds, of different chemical classes, are also being tested. Medicinal plants have been employed in the treatment of some cardiovascular diseases such as congestive heart failure and hypertension many centuries ago. Recently, the traditional remedies application for the treatment of different disorders is gaining revived popularity. In this chapter, we will investigate the efficacy and safety of natural products under preclinical studies and clinical trials with particular emphasis on their traditional uses and implementations in the primary health care system. The great potential of medicinal plants and herbs will be discussed in light of the rising prevalence of cardiovascular diseases as one of the most devastating global health problems.
Non-polar metabolites of green beans (Phaseolus vulgaris L.) potentiate the antidiabetic activity of mesenchymal stem cells in streptozotocin-induced diabetes in rats
(Wiely, 13/12/2021) Ezzat, Shahira M; Abdel Rahman, Mohamed F; Salama, Maha M; Mahrous, Engy A; El Bariary, Amany
Green beans (Phaseolus vulgaris L.) are consumed as pods or mature seeds (common beans). The pods were extracted with 95% ethanol and processed to prepare non- polar and polar fractions. Comparing the antihyperglycemic activity of both fractions, non-polar fraction (NPF, 200 mg kg−1 day−1) lowered blood glucose in streptozotocin diabetic rats by 65% compared to 57% for the polar fraction at the same dose. When NPF treatment was combined with injection of mesenchymal stem cells (MSC) a 4.4- fold increase in serum insulin and a 73.6% reduction in blood glucose were observed compared to untreated control. Additionally, a significant decrease in malondialde- hyde (76.2%), nitric oxide (68.2%), cholesterol (76.1%), and triglycerides (69.5%) and a 1.75-fold increase in HDL concentrations were observed in the group treated with this combination compared to diabetic animals. Interestingly, NPF increased homing of MSC in pancreas potentiating their antidiabetic activity. Finally, 26 compounds were identified in NPF using LC/MS analysis and four were isolated in pure form. The isolated compounds namely calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol showed good inhibitory activity against pancreatic lipase with IC50 at 1.93, 1.07, 1.34 and 1.44–1 μg/ml, respectively. Additionally, these compounds inhib- ited α-amylase, albeit at higher concentration, with IC50 at 248, 212, 254, and 155 μg/ ml for calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol, respec- tively. Our results suggest that green beans extract can potentiate effect of MSC in diabetes directly due to its own antidiabetic effect and indirectly by increasing MSC homing in pancreatic tissues. Practical applications It has been suggested in this study that green beans can improve hyperglycemia, oxi- dative balance in diabetes, so green beans can be promoted as a healthy nutrient for diabetic patients. Green beans also can enhance homing and differentiation of mesn- chymal stem cells in the pancreas for future stem cell therapy of type I diabetes.
A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing efect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line
(BioMed Central Ltd., 2023-10) Aborehab, Nora M; Salama, Maha M; Ezzat, Shahira M
Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung can- cers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purifcation of the 95% ethanolic extract of Thymus capitatus. Identifcation of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non- small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic efects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their signifcant efect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA signifcantly downregulated miRNA-21 expression. Meanwhile, the three com- pounds caused signifcant overexpression of Let-7 miRNA. This is the frst report on the anti-cancer activity of acetoxy- lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and diferentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer.
Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression
(Elsevier, 08/09/2021) Ezzat, Shahira M; Abdallah, Heba M.I; Yassen, Noha N; Radwan, Rasha A; Mostafa, Eman S; Salama, Maha M; Salem, Mohamed A
The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, β-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, β-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and β-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).
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.
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.