TY  - JOUR
A1  - Al-Warhi, Tarfah
A1  - Elmaidomy, Abeer H.
A1  - Maher, Sherif A.
A1  - Abu-Baih, Dalia H.
A1  - Selim, Samy
A1  - Albqmi, Mha
A1  - Al-Sanea, Mohammad M.
A1  - Alnusaire, Taghreed S.
A1  - Ghoneim, Mohammed M.
A1  - Mostafa, Ehab M.
A1  - Hussein, Shaimaa
A1  - El-Damasy, Ashraf K.
A1  - Saber, Entesar Ali
A1  - Elrehany, Mahmoud A.
A1  - Sayed, Ahmed M.
A1  - Othman, Eman M.
A1  - El-Sherbiny, Mohamed
A1  - Abdelmohsen, Usama Ramadan
T1  - The wound-healing potential of Olea europaea L. Cv. Arbequina leaves extract: an integrated in vitro, in silico, and in vivo investigation
JF  - Metabolites
N2  - Olea europaea L. Cv. Arbequina (OEA) (Oleaceae) is an olive variety species that has received little attention. Besides our previous work for the chemical profiling of OEA leaves using LC–HRESIMS, an additional 23 compounds are identified. An excision wound model is used to measure wound healing action. Wounds are provided with OEA (2% w/v) or MEBO\(^®\) cream (marketed treatment). The wound closure rate related to vehicle-treated wounds is significantly increased by OEA. Comparing to vehicle wound tissues, significant levels of TGF-β in OEA and MEBO\(^®\) (p < 0.05) are displayed by gene expression patterns, with the most significant levels in OEA-treated wounds. Proinflammatory TNF-α and IL-1β levels are substantially reduced in OEA-treated wounds. The capability of several lignan-related compounds to interact with MMP-1 is revealed by extensive in silico investigation of the major OEA compounds (i.e., inverse docking, molecular dynamics simulation, and ΔG calculation), and their role in the wound-healing process is also characterized. The potential of OEA as a potent MMP-1 inhibitor is shown in subsequent in vitro testing (IC\(_{50}\) = 88.0 ± 0.1 nM). In conclusion, OEA is introduced as an interesting therapeutic candidate that can effectively manage wound healing because of its anti-inflammatory and antioxidant properties.
KW  - olive
KW  - LC–HRESIMS
KW  - wound
KW  - Olea
KW  - TNF-α
KW  - virtual docking
KW  - TGF-β
KW  - MMP-1
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286150
SN  - 2218-1989
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Othman, Eman M.
A1  - Naseem, Muhammed
A1  - Awad, Eman
A1  - Dandekar, Thomas
A1  - Stopper, Helga
T1  - The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells
JF  - PLoS One
N2  - Modulating key dynamics of plant growth and development, the effects of the plant hormone cytokinin on animal cells gained much attention recently. Most previous studies on cytokinin effects on mammalian cells have been conducted with elevated cytokinin concentration (in the μM range). However, to examine physiologically relevant dose effects of cytokinins on animal cells, we systematically analyzed the impact of kinetin in cultured cells at low and high concentrations (1nM-10μM) and examined cytotoxic and genotoxic conditions. We furthermore measured the intrinsic antioxidant activity of kinetin in a cell-free system using the Ferric Reducing Antioxidant Power assay and in cells using the dihydroethidium staining method. Monitoring viability, we looked at kinetin effects in mammalian cells such as HL60 cells, HaCaT human keratinocyte cells, NRK rat epithelial kidney cells and human peripheral lymphocytes. Kinetin manifests no antioxidant activity in the cell free system and high doses of kinetin (500 nM and higher) reduce cell viability and mediate DNA damage in vitro. In contrast, low doses (concentrations up to 100 nM) of kinetin confer protection in cells against oxidative stress. Moreover, our results show that pretreatment of the cells with kinetin significantly reduces 4-nitroquinoline 1-oxide mediated reactive oxygen species production. Also, pretreatment with kinetin retains cellular GSH levels when they are also treated with the GSH-depleting agent patulin. Our results explicitly show that low kinetin doses reduce apoptosis and protect cells from oxidative stress mediated cell death. Future studies on the interaction between cytokinins and human cellular pathway targets will be intriguing.
KW  - DNA damage
KW  - apoptosis
KW  - oxidative stress
KW  - fluorescence recovery after photobleaching
KW  - lymphocytes
KW  - antioxidants
KW  - cell staining
KW  - cytokinins
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147983
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Fathy, Moustafa
A1  - Okabe, Motonori
A1  - Othman, Eman M.
A1  - Saad Eldien, Heba M.
A1  - Yoshida, Toshiko
T1  - Preconditioning of adipose-derived mesenchymal stem-like cells with eugenol potentiates their migration and proliferation in vitro and therapeutic abilities in rat hepatic fibrosis
JF  - Molecules
N2  - Mesenchymal stem cells (MSCs) have considerable therapeutic abilities in various disorders, including hepatic fibrosis. They may be affected with different culture conditions. This study investigated, on molecular basics, the effect of pretreatment with eugenol on the characteristics of adipose tissue-derived MSCs (ASCs) in vitro and the implication of eugenol preconditioning on the in vivo therapeutic abilities of ASCs against CCl\(_4\)-induced hepatic fibrosis in rats. The effect of eugenol on ASCs was assessed using viability, scratch migration and sphere formation assays. Expressions of genes and proteins were estimated by immunofluorescence or qRT-PCR. For the in vivo investigations, rats were divided into four groups: the normal control group, fibrotic (CCl\(_4\)) group, CCl\(_4\)+ASCs group and CCl\(_4\) + eugenol-preconditioned ASCs (CCl\(_4\)+E-ASCs) group. Eugenol affected the viability of ASCs in a concentration- and time-dependent manner. Eugenol improved their self-renewal, proliferation and migration abilities and significantly increased their expression of c-Met, reduced expression 1 (Rex1), octamer-binding transcription factor 4 (Oct4) and nanog genes. Furthermore, E-ASCs showed more of a homing ability than ASCs and improved the serum levels of ALT, AST, albumin, total bilirubin and hyaluronic acid more efficient than ASCs in treating CCl\(_4\)-induced hepatic fibrosis, which was confirmed with histopathology. More interestingly, compared to the CCl\(_4\)+ASCs group, CCl\(_4\)+E-ASCs group showed a lower expression of inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), cluster of differentiation 163 (CD163) and tumor necrosis factor-α (TNF-α) genes and higher expression of matrix metalloproteinase (MMP)-9 and MMP-13 genes. This study, for the first time, revealed that eugenol significantly improved the self-renewal, migration and proliferation characteristics of ASCs, in vitro. In addition, we demonstrated that eugenol-preconditioning significantly enhanced the therapeutic abilities of the injected ASCs against CCl\(_4\)-induced hepatic fibrosis.
KW  - adipose tissue-derived MSCs
KW  - eugenol
KW  - migration
KW  - self-renewal
KW  - hepatic fibrosis
KW  - CCl\(_4\)
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203662
SN  - 1420-3049
VL  - 25
IS  - 9
ER  - 
TY  - JOUR
A1  - Othman, Eman M.
A1  - Fathy, Moustafa
A1  - Bekhit, Amany Abdlrehim
A1  - Abdel-Razik, Abdel-Razik H.
A1  - Jamal, Arshad
A1  - Nazzal, Yousef
A1  - Shams, Shabana
A1  - Dandekar, Thomas
A1  - Naseem, Muhammad
T1  - Modulatory and toxicological perspectives on the effects of the small molecule kinetin
JF  - Molecules
N2  - Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.
KW  - cytokinin kinetin
KW  - modulatory effects
KW  - in vivo toxicity
KW  - A2a-R receptor
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223064
SN  - 1420-3049
VL  - 26
IS  - 3
ER  - 
TY  - JOUR
A1  - Balasubramanian, Srikkanth
A1  - Othman, Eman M.
A1  - Kampik, Daniel
A1  - Stopper, Helga
A1  - Hentschel, Ute
A1  - Ziebuhr, Wilma
A1  - Oelschlaeger, Tobias A.
A1  - Abdelmohsen, Usama R.
T1  - Marine sponge-derived Streptomyces sp SBT343 extract inhibits staphylococcal biofilm formation
JF  - Frontiers in Microbiology
N2  - Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.
KW  - medicine
KW  - marine sponges
KW  - actinomycetes
KW  - Streptomyces
KW  - staphilococci
KW  - biofilms
KW  - contact lens
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171844
VL  - 8
ER  - 
TY  - JOUR
A1  - Fathy, Moustafa
A1  - Darwish, Mostafa A.
A1  - Abdelhamid, Al-Shaimaa M.
A1  - Alrashedy, Gehad M.
A1  - Othman, Othman Ali
A1  - Naseem, Muhammad
A1  - Dandekar, Thomas
A1  - Othman, Eman M.
T1  - Kinetin ameliorates cisplatin-induced hepatotoxicity and lymphotoxicity via attenuating oxidative damage, cell apoptosis and inflammation in rats
JF  - Biomedicines
N2  - Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy.
KW  - cisplatin
KW  - hepatotoxicity
KW  - lymphotoxicity
KW  - oxidative stress
KW  - AKT
KW  - CD95
KW  - caspase-3
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281686
SN  - 2227-9059
VL  - 10
IS  - 7
ER  - 
TY  - JOUR
A1  - Cheng, Cheng
A1  - Othman, Eman M.
A1  - Stopper, Helga
A1  - Edrada-Ebel, RuAngelie
A1  - Hentschel, Ute
A1  - Abdelmohsen, Usama Ramadan
T1  - Isolation of petrocidin A, a new cytotoxic cyclic dipeptide from the marine sponge-derived bacterium \(Streptomyces\) sp. SBT348
JF  - Marine Drugs
N2  - A new cyclic dipeptide, petrocidin A (\(\textbf{1}\)), along with three known compounds—2,3-dihydroxybenzoic acid (\(\textbf{2}\)), 2,3-dihydroxybenzamide (\(\textbf{3}\)), and maltol (\(\textbf{4}\))—were isolated from the solid culture of \(Streptomyces\) sp. SBT348. The strain \(Streptomyces\) sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (\(\textbf{1}\)) and 2,3-dihydroxybenzamide (\(\textbf{3}\)) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products.
KW  - biology
KW  - sponges
KW  - actinomycetes
KW  - streptomyces
KW  - cyclic dipeptide
KW  - cytotoxic
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172644
VL  - 15
IS  - 12
ER  - 
TY  - JOUR
A1  - Naseem, Muhammad
A1  - Othman, Eman M.
A1  - Fathy, Moustafa
A1  - Iqbal, Jibran
A1  - Howari, Fares M.
A1  - AlRemeithi, Fatima A.
A1  - Kodandaraman, Geema
A1  - Stopper, Helga
A1  - Bencurova, Elena
A1  - Vlachakis, Dimitrios
A1  - Dandekar, Thomas
T1  - Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems
JF  - Scientific Reports
N2  - Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.
KW  - cytokinins
KW  - 6-benzylaminopurine
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231317
VL  - 10
ER  - 
TY  - JOUR
A1  - Fathy, Moustafa
A1  - Fawzy, Michael Atef
A1  - Hintzsche, Henning
A1  - Nikaido, Toshio
A1  - Dandekar, Thomas
A1  - Othman, Eman M.
T1  - Eugenol exerts apoptotic effect and modulates the sensitivity of HeLa cells to cisplatin and radiation
JF  - Molecules
N2  - Eugenol is a phytochemical present in different plant products, e.g., clove oil. Traditionally, it is used against a number of different disorders and it was suggested to have anticancer activity. In this study, the activity of eugenol was evaluated in a human cervical cancer (HeLa) cell line and cell proliferation was examined after treatment with various concentrations of eugenol and different treatment durations. Cytotoxicity was tested using lactate dehydrogenase (LDH) enzyme leakage. In order to assess eugenol’s potential to act synergistically with chemotherapy and radiotherapy, cell survival was calculated after eugenol treatment in combination with cisplatin and X-rays. To elucidate its mechanism of action, caspase-3 activity was analyzed and the expression of various genes and proteins was checked by RT-PCR and western blot analyses. Eugenol clearly decreased the proliferation rate and increased LDH release in a concentration- and time-dependent manner. It showed synergistic effects with cisplatin and X-rays. Eugenol increased caspase-3 activity and the expression of Bax, cytochrome c (Cyt-c), caspase-3, and caspase-9 and decreased the expression of B-cell lymphoma (Bcl)-2, cyclooxygenase-2 (Cox-2), and interleukin-1 beta (IL-1β) indicating that eugenol mainly induced cell death by apoptosis. In conclusion, eugenol showed antiproliferative and cytotoxic effects via apoptosis and also synergism with cisplatin and ionizing radiation in the human cervical cancer cell line.
KW  - eugenol
KW  - HeLa cells
KW  - cisplatin
KW  - radiation
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193227
SN  - 1420-3049
VL  - 24
IS  - 21
ER  - 
TY  - JOUR
A1  - Awad, Eman
A1  - Othman, Eman M.
A1  - Stopper, Helga
T1  - Effects of resveratrol, lovastatin and the mTOR-inhibitor RAD-001 on insulin-induced genomic damage in vitro
JF  - Molecules
N2  - Diabetes mellitus (DM) is one of the major current health problems due to lifestyle changes. Before diagnosis and in the early years of disease, insulin blood levels are elevated. However, insulin generates low levels of reactive oxygen species (ROS) which are integral to the regulation of a variety of intracellular signaling pathways, but excess levels of insulin may also lead to DNA oxidation and DNA damage. Three pharmaceutical compounds, resveratrol, lovastatin and the mTOR-inhibitor RAD-001, were investigated due to their known beneficial effects. They showed protective properties against genotoxic damage and significantly reduced ROS after in vitro treatment of cultured cells with insulin. Therefore, the selected pharmaceuticals may be attractive candidates to be considered for support of DM therapy.
KW  - genomic damage
KW  - insulin
KW  - resveratrol
KW  - lovastatin
KW  - mTOR-inhibitor RAD-001
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159260
VL  - 22
IS  - 12
ER  -