Browsing by Author "Aborehab, Nora M"

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Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR- 181a and apoptosis genes
(Academic Press Inc., 2023-07) Aborehab, Nora M; Abd-Elmawla, Mai A; ElSayed, Abeer M; Sabry, Omar; Ezzat, Shahira M; Abd-Elmawla, Mai A; ElSayed, Abeer M; Sabry, Omar
The aim of the present study is to explore the potential anticancer effect of the cardenolide; 2 acovenoside A against non-small cell lung cancer, understand its molecular mechanism in inducing 3 apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the 4 combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the 5 synergistic effect. The triple combination showed the best growth inhibition efficiency where the 6 number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The 7 combination also showed the most remarkable increase in gene expression of Bax and p53 and the least 8 level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell 9 lines treated with the combination. The present study has proven that the underlying mechanism of 10 acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions 11 which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present 12 study is the first to address the valuable effect of using acovenoside A together with carboplatin and 13 taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic ef
Alcohol-Induced Hepatic Fibrosis and the Relation between Hepcidin and Liver Fibrosis
(Suez Canal University, 2024-05) Ali, Al-shimaa A; Aborehab, Nora M; Saleh, Samy M; Mehanna, Eman T
Abstract: Alcoholic liver disease (ALD) is a worldwide health problem that may lead to development of fatty liver steatosis, hepatitis and cirrhosis. Alcohol is known to exert a harmful effect on a variety of human tissues. In particular, the liver is the major site of alcohol-induced damage because it is the direct recipient of the blood that contains elevated levels of alcohol, and it is the major organ responsible for alcohol metabolism. The damage caused by ethanol is mainly attributed to its metabolic process that results in production of acetaldehyde and reactive oxygen species (ROS) such as hydrogen peroxide, superoxide and free hydroxyl radical. These metabolites cause depletion of reduced glutathione (GSH), peroxidation of cellular membranes, oxidation of macro-molecules such as proteins and nucleic acids, and eventually lead to progressive injury of hepatocytes. Additionally, ethanol and its metabolic products enhance the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The enhanced production of those inflammation factors; stimulated partially by oxidative stress; results in cytokine imbalance and immune disorders, leading to further hepatic damage. Thus, agents with anti-inflammatory and anti-oxidative properties might be potential candidates for protection against alcohol-induced liver disease. The metabolic functions of the alcoholic liver are seriously affected. Disorders in iron metabolism are characteristic of ALD. Abnormal levels of iron, ferritin, and transferrin were reported in ALD. Hepcidin, the principle hepatic regulator of the metabolism of iron, is decreased in ALD.
Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats
(MDPI, 08/12/2021) Mehanna, Eman T; Ali, Al-Shimaa A; El-Shaarawy, Fatma; Mesbah, Noha M; Abo-Elmatty, Dina M; Aborehab, Nora M
This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 µg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.
An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line
(Nature Publishing Group, 2024-01) Sweed, Nabila M; Dawoud, Marwa H. S; Aborehab, Nora M; Ezzat, Shahira M
Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the efects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efciency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and fow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of − 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC50) values for FA from O2 and free FA were calculated against diferent cell lines showing a prominent IC50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 signifcantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P< 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer efect of FA against colorectal cancer, probably due to its enhanced solubility.Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy.
Artemisia spp.: An Update on Its Chemical Composition, Pharmacological and Toxicological Profiles
(Hindawi Publishing Corporation, 2022-09) Sharifi-Rad, Javad; Herrera-Bravo, Jesús; Semwal, Prabhakar; Painuli, Sakshi; Badoni, Himani; Ezzat, Shahira M; Farid, Mai M; Merghany, Rana M; Aborehab, Nora M; Salem, Mohamed A; Sen, Surjit; Acharya, Krishnendu; Lapava, Natallia; Martorell, Miquel; Tynybekov, Bekzat; Calina, Daniela; Cho, William C
Artemisia plants are traditional and ethnopharmacologically used to treat several diseases and in addition in food, spices, and beverages. The genus is widely distributed in all continents except the Antarctica, and traditional medicine has been used as antimalarial, antioxidant, anticancer, antinociceptive, anti-inflammatory, and antiviral agents. This review is aimed at systematizing scientific data on the geographical distribution, chemical composition, and pharmacological and toxicological profiles of the Artemisia genus. Data from the literature on Artemisia plants were taken using electronic databases such as PubMed/MEDLINE, Scopus, and Web of Science. Selected papers for this updated study included data about phytochemicals, preclinical pharmacological experimental studies with molecular mechanisms included, clinical studies, and toxicological and safety data. In addition, ancient texts and books were consulted. The essential oils and phytochemicals of the Artemisia genus have reported important biological activities, among them the artemisinin, a sesquiterpene lactone, with antimalarial activity. Artemisia absinthium L. is one of the most famous Artemisia spp. due to its use in the production of the absinthe drink which is restricted in most countries because of neurotoxicity. The analyzed studies confirmed that Artemisia plants have many traditional and pharmacological applications. However, scientific data are limited to clinical and toxicological research. Therefore, further research is needed on these aspects to understand the full therapeutic potential and molecular pharmacological mechanisms of this medicinal species.
Association of XIST/ miRNA155/Gab2/TAK1 cascade with the pathogenesis of anti‑phospholipid syndrome and its efect on cell adhesion molecules and infammatory mediators
(Nature Publishing Group, 2023-11) Abd‑Elmawla, Mai A; Elsabagh, Yumn A; Aborehab, Nora M
Anti-phospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and miscarriage events. Still, the molecular mechanisms underlying APS, which predisposes to a wide spectrum of complications, are being explored. Seventy patients with primary and secondary APS were recruited, in addition to 35 healthy subjects. Among APS groups, the gene expression levels of XIST, Gab2, and TAK1 were higher along with declined miRNA155 level compared with controls. Moreover, the sera levels of ICAM-1, VCAM-1, IL-1ꞵ, and TNF-α were highly elevated among APS groups either primary or secondary compared with controls. The lncRNA XIST was directly correlated with Gab2, TAK1, VCAM-1, ICAM-1, IL-1ꞵ, and TNF-α. The miRNA155 was inversely correlated with XIST, Gab2, and TAK1. Moreover, ROC curve analyses subscribed the predictive power of the lncRNA XIST and miRNA155, to diferentiate between primary and secondary APS from control subjects. The lncRNA XIST and miRNA155 are the upstream regulators of the Gab2/TAK1 axis among APS patients via infuencing the levels of VCAM-1, ICAM-1, IL1ꞵ, and TNF-α which propagates further infammatory and immunological streams. Interestingly, the study addressed that XIST and miRNA155 may be responsible for the thrombotic and miscarriage events associated with APS and provides new noninvasive molecular biomarkers for diagnosing the disease and tracking its progression.
Chondroprotection of fruit peels in a monosodium iodoacetate‐induced osteoarthritis rat model via downregulation of Col1A1
(Wiely, 04/03/2022) Aborehab, Nora M; El Bishbishy, Mahitab H
The potential of the fruit peels of mango, orange, cantaloupe, and pomegranate in the treatment of osteoarthritis (OA) was evaluated in a rat model. Their metabolic profiles were characterized using ultrahigh‐performance liquid chromatography (UPLC)–electrospray ionization‐mass spectroscopy and 66 albino rats were intra‐ articularly injected with monosodium iodoacetate in the knee joints. The extracts were orally administered at doses of 200 and 400 mg/kg for 28 days. Serum levels of IL‐6 and tissue levels of cyclooxygenase‐2 (COX‐2), peroxisome proliferator‐ activated receptor‐gamma (PPARγ), and alpha‐smooth muscle actin (α‐SMA) were measured using ELISA. COL1A1 expression was measured by quantitative polymerase chain reaction. Histopathological changes in the joints were examined. In the extracts, 85 metabolites were annotated, and the levels of interleukin (IL)‐6, COX‐2, α‐SMA, malondialdehyde, and nitric oxide were significantly reduced, while PPARγ and glutathione levels were significantly raised in all treated groups compared to the OA group. All extracts downregulated the cartilage mRNA expressions for COL1A1 dose‐dependently. Mango peel extract exhibited the best chondroprotective effect. The in silico study showed the link between mango extract metabolites and COX‐2.
Circular SERPINA3 and its target microRNA-944 as potential molecular biomarkers in hepatitis C virus-induced hepatocellular carcinoma in Egyptian population
(KeAi Communications Co., 2023-06) Aborehab, Nora M; Kandeil, Mohamed A; Sabry, Dina; Rabie, Radwa; Ibrahim, Ibrahim T
Background: The most prevalent cancer in Egypt is hepatocellular carcinoma (HCC) mainly due to the infection with the hepatitis C virus. So it is critical to find sensitive biomarkers for early diagnosis of HCC and avoid post- operation tumor recurrence. Therefore, this research was designed to demonstrate the circSERPINA3 role in the regulation of microRNA-944 gene expression in HCV-related HCC cases and compare these results with circ- SERPINA3 and microRNA-944 gene expression levels in HCV-infected patients. Methodology: Study participants were divided into three groups: healthy controls, HCV- infected, and HCV- induced HCC patients. The gene expression levels of circSERPINA3 and microRNA-944 were evaluated using Real-Time qPCR. Then the immunoblotting procedure was applied to measure the serum levels of MDM2 and E- cadherin besides, the serum concentration levels of glypican-3 and alpha-fetoprotein were measured by sandwich ELISA. Results: The gene expression level of circSERPINA3 was significantly upregulated in both HCV-infected and HCC patients causing suppression of the antitumor effect of miR-944 and showing a lower 1-year survival rate than the participants who had low circSERPINA3 gene expression levels. Subsequently, the miR-944 downstream protein, MDM2 was remarkably upregulated, exaggerating the metastasis and oxidative stress in HCC cases. Additionally, the results confirmed the downregulation of microRNA-944 improved the progression of viral hepatitis C cases to hepatocarcinogenesis through the significantly increased plasma level of the metastatic marker, E-cadherin. Although alpha-fetoprotein is a common diagnostic marker used in the diagnosis of HCC, our results showed that glypican-3 had greater sensitivity and specificity and positively correlated to the IGF-1 signaling pathway of HCC cases. Moreover, the relative expression levels of circSERPINA3 and E-cadherin in both the HCV and HCV-induced HCC were significantly positively correlated. Conclusion: circSERPINA3 and miR-944 were sensitive molecular markers for early diagnosis of HCC and could be prospective treatment targets for HCV-infected patients to avoid tumor recurrence in HCC cases.
Coriander (Coriandrum sativum L.) essential oil and oil‑loaded nano‑formulations as an anti‑aging potentiality viaTGFβ/SMAD pathway
(Springer nature, 2022-04) Salem, Mohamed A; Manaa, Eman G; Osama, Nada; Aborehab, Nora M; Ragab, Mai F; Haggag, Yusuf A; Ibrahim, Magda T; Hamdan, Dalia I
Aging has become a concern for many people, especially women. Given that high-quality anti-aging products are of high cost; it has imperative to search for other economical sources. Essential oils are frequently used in cosmetics products due to a wide range of biological activities as well as their pleasant odor. The current study aimed to investigate the biochemical efect of the cosmetic potential of selected Apiaceous essential oils, traditionally used for skincare, by evaluating their anti-wrinkle activity. It is worth noting that, coriander essential oil showed the highest collagenase, elastase, tyrosinase, and hyaluronidase inhibitory activities compared to other Apiaceous oils (fennel, anise, and cumin). GC–MS proved that coriander essential oil showed a very high level of oxygenated monoterpenes, with linalool (81.29%) as the most abundant constituent. Intriguingly, coriander oil cream and Coriander Essential Oil-loaded Lipid Nanoparticles (CEOLNs) formulations attenuated in vivo UV-induced skin photoaging that was manifested by signifcantly decreased MDA, COX-2, PGE- 2, MMP-1, JNK, and AP-1 levels. Moreover, these pharmaceutical dosage forms signifcantly increased skin collagen content compared to UV-injured group. Also, coriander essential oil signifcantly increased TGFβ, TGFβII, and SMAD3 protein expression levels compared to UV-injured group. In conclusion, the pharmaceutical dosage forms of coriander oil possess anti-wrinkle activities that could have an auspicious role in amending extrinsic aging.
Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation
(Multidisciplinary Digital Publishing Institute (MDPI), 2022-10) Ezzat, Shahira M; Teba, Heba El Sayed; Shahin, Inas G; Hafez, Ahmed M; Kamal, Aliaa M; Aborehab, Nora M
: A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and eval- uation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage. :
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.
Metabolomics driven analysis of Nigella sativa seeds identifies the impact of roasting on the chemical composition and immunomodulatory activity
(Elsevier Ltd., 2022-08-07) Salem, Mohamed A; El-Shiekh, Riham A; Aborehab, Nora M; Al‐Karmalawy, Ahmed A; Ezzat, Shahira M; Alseekh, Saleh; Fernie, Alisdair R
Nigella sativa L. seeds (NS) are known as one of the most traditional immunomodulatory and nutritive food additives. NS can, furthermore, be roasted to give curries, breads, and other dishes a smoky, nutty flavor. This study evaluated the effect of roasting NS on the metabolic profile and immunomodulatory activity. Non-targeted metabolomics analysis was conducted using several analytical platforms, including GC-MS and UPLC-MS. A total of 197 metabolites were identified, belonging to different classes such as saponins, alkaloids, flavonoids, and lipids. In vitro immunomodulatory activity on the differentiated monocytic cell line THP-1 was assessed, revealing that the roasted seeds showed significantly-decreased immunomodulatory activity. Furthermore, a molecular docking study, which was carried out against immunomodulation- related pathway protein (iNOS), revealed that compounds which showed the best binding scores were severely decreased by roasting. Conclusively, our results demonstrate that the roasting of NS results in severe losses in their bioactive metabolites and immunomodulatory activity.
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.
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.
The Pharmacological Activities of Crocus sativus L.: A Review Based on the Mechanisms and Therapeutic Opportunities of its Phytoconstituent
(Hindawi, 14/02/2022) Butnariu, Monica; Quispe, Cristina; Herrera-Bravo, Jesús; Sharifi-Rad, Javad; Singh, Laxman; Aborehab, Nora M; Bouyahya, Abdelhakim; Venditti, Alessandro; Sen, Surjit; Acharya, Krishnendu; Bashiry, Moein; Ezzat, Shahira M; Setzer, William N; Martorell, Miquel; Mileski, Ksenija S; Bagiu, Iulia-Cristina; Docea, Anca Oana; Calina, Daniela; Cho, William C
Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western Asia, used in gardens and parks as ornamental plants, while Crocus sativus L. (saffron) is the only species that is cultivated for edible purpose. The use of saffron is very ancient; besides the use as a spice, saffron has long been known also for its medical and coloring qualities. Due to its distinctive flavor and color, it is used as a spice, which imparts food preservative activity owing to its antimicrobial and antioxidant activity. This updated review discusses the biological properties of Crocus sativus L. and its phytoconstituents, their pharmacological activities, signaling pathways, and molecular targets, therefore highlighting it as a potential herbal medicine. Clinical studies regarding its pharmacologic potential in clinical therapeutics and toxicity studies were also reviewed. For this updated review, a search was performed in the PubMed, Science, and Google Scholar databases using keywords related to Crocus sativus L. and the biological properties of its phytoconstituents. From this search, only the relevant works were selected. The phytochemistry of the most important bioactive compounds in Crocus sativus L. such as crocin, crocetin, picrocrocin, and safranal and also dozens of other compounds was studied and identified by various physicochemical methods. Isolated compounds and various extracts have proven their pharmacological efficacy at the molecular level and signaling pathways both in vitro and in vivo. In addition, toxicity studies and clinical trials were analyzed. The research results highlighted the various pharmacological potentials such as antimicrobial, antioxidant, cytotoxic, cardioprotective, neuroprotective, antidepressant, hypolipidemic, and antihyperglycemic properties and protector of retinal lesions. Due to its antioxidant and antimicrobial properties, saffron has proven effective as a natural food preservative. Starting from the traditional uses for the treatment of several diseases, the bioactive compounds of Crocus sativus L. have proven their effectiveness in modern pharmacological research. However, pharmacological studies are needed in the future to identify new mechanisms of action, pharmacokinetic studies, new pharmaceutical formulations for target transport, and possible interaction with allopathic drugs.
Potential Valorization of Edible Nuts By-Products: Exploring the Immune-Modulatory and Antioxidants Effects of Selected Nut Shells Extracts in Relation to Their Metabolic Profiles
(MDPI, 25/02/2022) Salem, Mohamed A; Aborehab, Nora M; Al-Karmalawy, Ahmed A; Fernie, Alisdair R; Alseekh, Saleh; Ezzat, Shahira M
The immune system is a potent army that defends our body against various infections and diseases through innate and adaptive immunity. Herbal medicine is one of the essential sources for enhancing immunity because of affordability, availability, minor side effects, and consumers’ preferences. Hazelnuts, walnuts, almonds, and peanuts are among the most widespread edible nuts that are rich in phenolics, fats, fibers, vitamins, proteins, and minerals. The potential of nut shells in phytoremediation has attracted increasing attention as a sustainable solution for waste recycling. Here, we determined the in vitro immune-modulatory activity as well as the metabolite profile of the four nut shell extracts. The addition of the extracts to LPS-stimulated macrophages, especially peanut and walnut shells, has downregulated the gene expression of AP-1, TNF-α, IL-8, iNOS, and COX-2 expression levels. Significant antioxidant capabilities and immune-modulatory effects have been traced for peanut shells. UPLC-MS metabolic profiling of the four nut shell extracts allowed the detection of a relatively high level of phenolic compounds in peanut shells. Intriguingly, a significant correlation between the antioxidant capacity and the total phenolic content was found, indicating the contribution of the phenolic compounds to the antioxidant properties and hence the immune-modulatory activity. Furthermore, molecular docking and structure–activity relationship (SAR) studies revealed kaempferol rutinoside and proanthocyanidin A5’ as potential iNOS inhibitors.
Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation
(King Saud University, 2024-02) Alyami, Mohammad H; Hamdan, Dalia I; Khalil, Heba M.A; Orabi, Mohamed A.A; Aborehab, Nora M; Osama, Nada; Abdelhafez, Mai M; Al-Mahallawi, Abdulaziz Mohsen; Alyami, Hamad S
Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats’ model with ovalbumin-induced allergic asthma. R. graveolens extract and RutaND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-β, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative antiallergic asthma drug.
Untargeted metabolomics-based molecular networking for chemical characterization of selected Apiaceae fruit extracts in relation to their antioxidant and anti-cellulite potentials
(Elsevier, 2023-12) Hegazia, Nesrine M; Salemb, Mohamed A; Saad, Hamada H; Aborehab, Nora M; El Bishbishy, Mahitab H; Ezzat, Shahira M
Stress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management.
Upregulation of MC4R and PPAR-α expression mediates the anti-obesity activity of Moringa oleifera Lam. in high-fat diet-induced obesity in rats
(Elsevier Ireland Ltd, 01/01/2020) Ezzat, Shahira M; El Bishbishy, Mahitab H.; Aborehab, Nora M; Salama, Maha M.; Hasheesh, Adel; Abdel Motaal, Amira; Rashad, Hend; Metwally, Fateheya M
Ethnopharmacological relevance: various extracts of Moringa oleifera Lam. leaves, were reported to possess antiobesity effect in experimental animals models, yet its active doses and mechanism of action are still unclear. Materials and methods: The metabolic profiling of 70% ethanol extract of M. oleifera (MO) leaves was performed using HPLC-MS/MS analysis. The antiobesity activity of MO was tested in high fat diet induced obesity in rats at 200 and 400 mg/kg body weight orally for 1 month. Total cholesterol (TC), high density lipoproteins (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGs), insulin resistance, insulin sensitivity, and adipose tissue index were monitored. In addition, fatty acid synthase (FAS) and HMG-CoA reductase mRNA from liver tissue, Peroxisome Proliferator-Activated Receptor alpha (PPARα) and Melanocortin-4 receptor (MC4R) RNA from adipose tissue were quantified using qRT-PCR. MO hard gelatin capsules (400 mg/capsule) were formulated and standardized using HPLC-RP analysis and tested on fifteen female participants, aged 45–55 with a BMI of 29–34 kg/m2. Results: Thirteen metabolites were tentatively identified using HPLC-MS/MS analysis including flavonols, flavones and a phenolic acid. MO 400 showed a prominent effect on reducing the rats’ final weights, % weight increase and adiposity index (P < 0.05). Glucose, insulin and HOMA-IR were significantly reduced and R-QUICKI was significantly increased by MO 400 (P < 0.001). Mean tissue level of leptin and vaspin were significantly reduced, adiponectin, omentin and GLUT-4 expression were increased significantly by MO 400 (P < 0.01). MO 400 significantly suppressed FAS and HMG-CoA reductase and increased mRNA expression of MC4R and PPAR-α (P < 0.01). Eight weeks administration of MO hard gelatin capsules to obese patients showed significant reduction of the average BMI, TC and LDL compared to the baseline values (p < 0.05). Conclusion: Our results presented a scientific evidence for the traditional use of M. oleifera leaves as antiobesity herbal medicine