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  1. Article ; Online: Acidic Exo-Polysaccharide Obtained from Bacillus sp. NRC5 Attenuates Testosterone-DMBA-Induced Prostate Cancer in Rats via Inhibition of 5 α-Reductase and Na+/K+ ATPase Activity Mechanisms

    Ibrahim, Abeer Y. / Mahmoud, Manal G. / Asker, Mohsen S. / Youness, Eman R. / El-Newary, Samah A.

    Curr Microbiol. 2023 Jan., v. 80, no. 1 p.8-8

    2023  

    Abstract: Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product ... ...

    Abstract Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product feasible for prostate cancer therapies. The anti-prostate cancer of acidic exo-polysaccharide produced from marine Bacillus sp. NRC5 (EBPS) was determined using 7,12-dimethylbenz-(a)-anthracene; DMBA-induced prostate cancer in male Sprague Dawley rats. Rats were subcutaneously injected with testosterone (3 mg/kg/day for 3 months) and a single dose of DMBA (65 mg/kg) for induction of prostate cancer. EBPS was administrated orally at dose 200 mg/kg/day for 3 months. To study protective effect of EBPS, animals received EBPS before cancer induction, meanwhile in therapeutic effect animals received EBPS after cancer induction. EBPS debug oxidative stress and inflammatory conditions associated with prostate cancer. EBPS either protective or therapeutic material considerably reduced cancer growth rate-limiting enzyme—i.e., 5-α-reductase (46.89 ± 1.72 and 44.86 ± 2.56 µg Eq/mL) and Na⁺/K⁺ ATPase (0.44 ± 0.03 and 0.42 ± 0.02 µg Eq/mL), compared to cancer control (69.68 ± 3.46 µg Eq/mL). In addition, both cancer biomarkers—i.e., prostate-specific antigen and carcinoembryonic antigen were significantly lowered as evidence of the ability of EBPS to protect and treat prostate cancer in chemically induced rats. EBPS showed protective and therapeutic efficacy on testosterone–DMBA-induced prostate cancer rats with a good safety margin. This study may go to clinical trials after a repeated study on another type of small experimental animal, their offspring, and one big experimental animal.
    Keywords Bacillus (bacteria) ; adenosinetriphosphatase ; antigens ; antioxidants ; exopolysaccharides ; laboratory animals ; males ; oxidative stress ; progeny ; prostate-specific antigen ; prostatic neoplasms ; protective effect ; sodium-potassium-exchanging ATPase ; testosterone ; therapeutics
    Language English
    Dates of publication 2023-01
    Size p. 8.
    Publishing place Springer US
    Document type Article ; Online
    ZDB-ID 134238-1
    ISSN 1432-0991 ; 0343-8651
    ISSN (online) 1432-0991
    ISSN 0343-8651
    DOI 10.1007/s00284-022-03098-8
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  2. Article ; Online: Acidic Exo-Polysaccharide Obtained from Bacillus sp. NRC5 Attenuates Testosterone-DMBA-Induced Prostate Cancer in Rats via Inhibition of 5 α-Reductase and Na

    Ibrahim, Abeer Y / Mahmoud, Manal G / Asker, Mohsen S / Youness, Eman R / El-Newary, Samah A

    Current microbiology

    2022  Volume 80, Issue 1, Page(s) 8

    Abstract: Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product ... ...

    Abstract Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product feasible for prostate cancer therapies. The anti-prostate cancer of acidic exo-polysaccharide produced from marine Bacillus sp. NRC5 (EBPS) was determined using 7,12-dimethylbenz-(a)-anthracene; DMBA-induced prostate cancer in male Sprague Dawley rats. Rats were subcutaneously injected with testosterone (3 mg/kg/day for 3 months) and a single dose of DMBA (65 mg/kg) for induction of prostate cancer. EBPS was administrated orally at dose 200 mg/kg/day for 3 months. To study protective effect of EBPS, animals received EBPS before cancer induction, meanwhile in therapeutic effect animals received EBPS after cancer induction. EBPS debug oxidative stress and inflammatory conditions associated with prostate cancer. EBPS either protective or therapeutic material considerably reduced cancer growth rate-limiting enzyme-i.e., 5-α-reductase (46.89 ± 1.72 and 44.86 ± 2.56 µg Eq/mL) and Na
    MeSH term(s) Animals ; Male ; Rats ; Bacillus ; Cholestenone 5 alpha-Reductase/metabolism ; Ions ; Rats, Sprague-Dawley ; Testosterone/adverse effects ; Polysaccharides, Bacterial/pharmacology ; Prostatic Neoplasms/chemically induced ; Prostatic Neoplasms/therapy ; Sodium-Potassium-Exchanging ATPase/metabolism
    Chemical Substances Cholestenone 5 alpha-Reductase (EC 1.3.1.22) ; Ions ; Testosterone (3XMK78S47O) ; exopolysaccharide, Bacillus ; Polysaccharides, Bacterial ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2022-11-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 134238-1
    ISSN 1432-0991 ; 0343-8651
    ISSN (online) 1432-0991
    ISSN 0343-8651
    DOI 10.1007/s00284-022-03098-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Characterization and in-vitro Alzheimer's properties of exopolysaccharide from Bacillus maritimus MSM1.

    Selim, Manal S / Mohamed, Sahar S / Asker, Mohsen S / Ibrahim, Abeer Y / El-Newary, Samah A / El Awady, Mohamed E

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 11399

    Abstract: Four bacterial isolates were obtained from marine sediments collected from Sahl Hashish, Hurghada Red Sea, Egypt. This study was designed to search for promising anti-Alzheimer natural polysaccharide; therefore, four isolates were screened for ... ...

    Abstract Four bacterial isolates were obtained from marine sediments collected from Sahl Hashish, Hurghada Red Sea, Egypt. This study was designed to search for promising anti-Alzheimer natural polysaccharide; therefore, four isolates were screened for exopolysaccharides (EPSs) production and acetylcholinesterase inhibition. The isolate S16 provided the highest EPS yield (7.51 g/L) and acetylcholinesterase inhibition. It was identified morphologically and genetically using 16S rRNA gene sequence analysis as Bacillus maritimus. A Physicochemical analysis of S16 exopolysaccharide (BMEPS) was estimated, which pointed to the presence of uronic acid and sulfate (24.7% and 18.3%, respectively). HPLC analysis indicated that mannuronic acid, glucuronic acid, glucose, and mannose are presented in a molar ratio of 0.8:1.0:2.8:2.3, respectively. Furthermore, FT-IR revealed an abundance of β-configurations. The GPC estimated the average molecular weight (Mw) as 4.31 × 10
    MeSH term(s) Acetylcholinesterase ; RNA, Ribosomal, 16S/genetics ; Spectroscopy, Fourier Transform Infrared ; Bacillus ; Antioxidants/chemistry ; Cholinesterase Inhibitors/chemistry
    Chemical Substances Acetylcholinesterase (EC 3.1.1.7) ; RNA, Ribosomal, 16S ; Antioxidants ; Cholinesterase Inhibitors
    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-38172-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of biologically active exopolysaccharide produced by Streptomyces sp. NRCG4 and its anti-Alzheimer efficacy: in-vitro targets.

    Mahmoud, Manal G / Awady, Mohamed E El / Selim, Manal S / Ibrahim, Abeer Y / Ibrahim, Faten M / Mohamed, Sahar S

    Journal, genetic engineering & biotechnology

    2023  Volume 21, Issue 1, Page(s) 76

    Abstract: Background: Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and ... ...

    Abstract Background: Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and structures because of their special living conditions. Polysaccharides from marine microorganisms are of interest to new drug discovery.
    Results: The current research focused on the isolation of bacteria from Red Sea, Egypt, that have the ability to produce a new natural exopolysaccharide in order to be examined in treating Alzheimer's illness to obviate side effects of synthetic drugs. Properties of exopolysaccharide (EPS) produced by an isolated Streptomyces strain were investigated for its capability to play as anti-Alzheimer. This strain was identified morphologically, physiologically, and biochemically and actually was confirmed by molecularly 16S rRNA analysis as Streptomyces sp. NRCG4 with accession number MK850242. The produced EPS was fractionated by precipitation 1:4 volumes of chilled ethanol and the third major fraction (1:3) listed as NRCG4, and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), high-performance gel permeation chromatography (HPGPC), and high-performance liquid chromatography (HPLC). The findings showed that NRCG4 was an acidic EPS composed of mannuronic acid, glucose, mannose, and rhamnose in a molar ratio of 1.2:1.5:2.8:1.0, respectively. NRCG4 Mw was determined to be 4.25 × 10
    Conclusions: The present study highlighted those exopolysaccharides could be harnessed to improve pharmaceutical industry (anti-Alzheimer, anti-tyrosinase, anti-inflammatory, and antioxidant agents).
    Language English
    Publishing date 2023-07-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2637420-1
    ISSN 2090-5920 ; 1687-157X ; 2090-5920
    ISSN (online) 2090-5920
    ISSN 1687-157X ; 2090-5920
    DOI 10.1186/s43141-023-00530-9
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  5. Article ; Online: Production, structural and biochemical characterization relevant to antitumor property of acidic exopolysaccharide produced from Bacillus sp. NRC5.

    Mohamed, Sahar S / Ibrahim, Abeer Y / Asker, Mohsen S / Mahmoud, Manal G / El-Newary, Samah A

    Archives of microbiology

    2021  Volume 203, Issue 7, Page(s) 4337–4350

    Abstract: This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and ... ...

    Abstract This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and anticancer have been studied. BEPS was evaluated as an anti-inflammatory in vitro against cyclooxygenase (COX-1 and COX-2) and evaluated as an anticancer on human breast and prostate cancer cell lines (MCF-7 and PC3). In addition, BEPS antitumor activity was tested against the Ehrlich Ascites Carcinoma (EAC) model. The BEPS presented potent antioxidant activities, consisted of glucose, mannose, and mannuronic acid in a molar ratio of 1.0:1.7:0.8 with a molecular weight of 3.59 × 10
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Antioxidants/pharmacology ; Bacillus/chemistry ; Bacillus/metabolism ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Humans ; Longevity/drug effects ; Mice ; Polysaccharides, Bacterial/biosynthesis ; Polysaccharides, Bacterial/chemistry ; Polysaccharides, Bacterial/pharmacology
    Chemical Substances Antineoplastic Agents ; Antioxidants ; Polysaccharides, Bacterial ; exopolysaccharide, Bacillus
    Language English
    Publishing date 2021-06-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 124824-8
    ISSN 1432-072X ; 0302-8933
    ISSN (online) 1432-072X
    ISSN 0302-8933
    DOI 10.1007/s00203-021-02422-3
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  6. Article: Production, structural and biochemical characterization relevant to antitumor property of acidic exopolysaccharide produced from Bacillus sp. NRC5

    Mohamed, Sahar S. / Ibrahim, Abeer Y. / Asker, Mohsen S. / Mahmoud, Manal G. / El-Newary, Samah A.

    Archives of microbiology. 2021 Sept., v. 203, no. 7

    2021  

    Abstract: This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and ... ...

    Abstract This study targeted the production of exopolysaccharide from Bacillus sp. NRC5 grown in Egyptian seawater to use it as natural antitumor therapy. The biological activities of selected exopolysaccharide (BEPS) as an antioxidant, anti-inflammatory and anticancer have been studied. BEPS was evaluated as an anti-inflammatory in vitro against cyclooxygenase (COX-1 and COX-2) and evaluated as an anticancer on human breast and prostate cancer cell lines (MCF-7 and PC3). In addition, BEPS antitumor activity was tested against the Ehrlich Ascites Carcinoma (EAC) model. The BEPS presented potent antioxidant activities, consisted of glucose, mannose, and mannuronic acid in a molar ratio of 1.0:1.7:0.8 with a molecular weight of 3.59 × 10⁵ g/mol. BEPS showed a promising COX-2 inhibitory effect in comparison with the reference drug celecoxib. BEPS appeared efficient anticancer property, where it killed 64.20 and 70.20% of MCF-7 and PC3 cells at 100 µg/ml, respectively (IC₅₀, 76.70, and 70.40 µg/ml, respectively). BEPS exhibited antitumor ability as it prolonged the lifespan of mice to reach 75 days instead of 20 days in the tumor control, reduced viable cancer cells count, tumor volume and weight, modulated blood components, and white blood cells differentiation. BEPS produced from Bacillus sp. NRC5 showed its antioxidant and anti-inflammatory abilities and antitumor abilities, which may all be attributed to its unique composition containing sulfated moieties and uronic acids.
    Keywords Bacillus (bacteria) ; antineoplastic activity ; antioxidants ; ascites ; breasts ; cancer therapy ; carcinoma ; drugs ; exopolysaccharides ; glucose ; humans ; longevity ; mannose ; microbiology ; models ; molecular weight ; neoplasm cells ; prostaglandin synthase ; prostatic neoplasms ; seawater
    Language English
    Dates of publication 2021-09
    Size p. 4337-4350.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    ZDB-ID 124824-8
    ISSN 1432-072X ; 0302-8933
    ISSN (online) 1432-072X
    ISSN 0302-8933
    DOI 10.1007/s00203-021-02422-3
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  7. Article: Vitex agnus-castus L. (Chasteberry) extracts shows in vitro and in vivo anti-inflammatory and anti-tumor propensities via reduction of cyclooxygenase-2 activity and oxidative stress complications

    Ibrahim, Faten M / Ibrahim, Abeer Y / El-Newary, Samah A / Hendawy, Saber F / Mahomoodally, Mohamad F

    SAAB South African journal of botany. 2021 Feb. 04,

    2021  

    Abstract: Vitex agnus-castus, is a famous botanical remedy and a nutritional supplement to manage a panoply of human ailments. The impact of V. agnus-castus fruits aqueous-alcoholic crude extract and its fractions were evaluated for possible in vitro antioxidant, ... ...

    Abstract Vitex agnus-castus, is a famous botanical remedy and a nutritional supplement to manage a panoply of human ailments. The impact of V. agnus-castus fruits aqueous-alcoholic crude extract and its fractions were evaluated for possible in vitro antioxidant, anti-inflammatory, and in vivo antitumor efficacy. The inhibitory action of the tested extract and fractions on cyclooxygenase enzymes (COX-1&2) were assessed. In addition, scavenging ability on different radicals and molecule were evaluated together with the chelating character, lipid peroxide inhibitory action and reducing power. The efficient fraction was then evaluated for possible anti-tumor agent in immunomodulatory model (Ehrlich Ascites Carcinoma). The aqueous-alcoholic extract and ethyl acetate fractions significantly (p<0.05) and selectively suppressed COX-2 (IC₅₀=100 and 110 µg/ml, respectively). The crude extract and its fractions showed promising radical scavenging properties. The two crude vitex extracts significantly reduced the viable Ehrlich cell count and increased non-viable cells also improved the hematological indicators. These ameliorations were obvious from the increasing median survival time and a marked increase in life span. It is argued that the anti-tumor activity of vitex fruits crude extract may be qualified to its anti-inflammatory activity against COX-2, which leads to a reduction in prostaglandin production. Overall, these anti-tumor results for vitex crude aqueous-alcoholic extract can be justified on the antioxidant/anti-inflammatory properties. This study tend to show that vitex extract/fractions possess anti-inflammatory, antioxidant propensities and cyclooxygenase inhibitory properties which could justify the promising antitumor properties and be further studied in the development of biomedicine.
    Keywords Vitex agnus-castus ; anti-inflammatory activity ; antineoplastic activity ; antineoplastic agents ; ascites ; carcinoma ; ethyl acetate ; humans ; lipid peroxides ; longevity ; medicine ; models ; oxidative stress ; prostaglandin synthase ; prostaglandins
    Language English
    Dates of publication 2021-0204
    Publishing place Elsevier B.V.
    Document type Article
    Note NAL-AP-2-clean ; Pre-press version
    ZDB-ID 2126918-X
    ISSN 0254-6299
    ISSN 0254-6299
    DOI 10.1016/j.sajb.2021.02.001
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  8. Article: Acidic Exopolysaccharide Produced from Marine

    Ibrahim, Abeer Y / Youness, Eman R / Mahmoud, Manal G / Asker, Mohsen S / El-Newary, Samah A

    Breast cancer : basic and clinical research

    2020  Volume 14, Page(s) 1178223420902075

    Abstract: Purpose: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine : Methods: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically ... ...

    Abstract Purpose: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine
    Methods: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA).
    Results: 7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na
    Conclusion: The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.
    Language English
    Publishing date 2020-01-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2423804-1
    ISSN 1178-2234
    ISSN 1178-2234
    DOI 10.1177/1178223420902075
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  9. Article: Antioxidant, cytotoxicity and anti-tumor activity of Cordia dichotoma fruits accompanied with its volatile and sugar composition

    Ibrahim, Abeer Y / El-Newary, Samah A / Ibrahim, Gamil E

    Annals of agricultural science. 2019 June, v. 64, no. 1

    2019  

    Abstract: The aim of the present research was to investigate the chemical composition, antioxidant and anti-tumor effects of Cordia dichotoma fruit pulp extract “CDFP-extract”. Day after intraperitoneal inoculation of Ehrlich ascites carcinoma (EAC) cells in mice, ...

    Abstract The aim of the present research was to investigate the chemical composition, antioxidant and anti-tumor effects of Cordia dichotoma fruit pulp extract “CDFP-extract”. Day after intraperitoneal inoculation of Ehrlich ascites carcinoma (EAC) cells in mice, CDFP-extract was administered orally at 500 mg/kg body weight (equal to 0.10 of determined LD50) for ten consecutive days. CDFP-extract contains 112.71 ± 8.40 mg gallic acid/g, 69.76 ± 4.18 mg quercetin/g, 25.65 ± 1.80 mg catechin/g, 70.90 ± 2.92 mg total alkaloids/g extract. The high-performance liquid chromatography (HPLC) analysis for sugar determination showed that glucouronic acid was the main compound (34.08%) followed by sucrose, glucose, and fructose by 25.61%, 11.82%, and 8.95%, respectively. The gas-liquid chromatography (GC) and GC‐MS of the fruit showed that the presence of 19 volatile compounds were identified. The main constituents of the extract were bornyl acetate, α-terpineol, linaly butyrate, and α-phellandrene. The CDFP-extract showed a powerful effect in scavenging superoxide radicals and chelating metals ions as well as high reduction capability and total antioxidant capacity, dose-dependent manner. On the other hand, the viable Ehrlich cell count and solid tumor weight were significantly reduced by administration of CDFP extract and it increased non-viable cells. The CDFP-extract ameliorated all hematological parameters, this amelioration reflected on increasing median survival time and significant increase (p < 0.05) in life span. CDFP-extract appeared in antioxidant and anti-tumor activities. The anti-tumor activity of CDFP-extract may be attributed to phenols, flavonoids, tannins and glucouronic acid contents that are documented as an antioxidant, anti-inflammatory, and antitumor agents.
    Keywords alkaloids ; alpha-phellandrene ; alpha-terpineol ; antineoplastic activity ; antineoplastic agents ; antioxidant activity ; ascites ; body weight ; bornyl acetate ; butyrates ; carcinoma ; catechin ; chemical composition ; Cordia dichotoma ; cytotoxicity ; dose response ; fructose ; fruit pulp ; fruits ; gallic acid ; gas chromatography-mass spectrometry ; glucose ; hematologic tests ; high performance liquid chromatography ; ions ; lethal dose 50 ; longevity ; metals ; mice ; phenols ; quercetin ; sucrose ; superoxide anion ; tannins ; volatile compounds
    Language English
    Dates of publication 2019-06
    Size p. 29-37.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 418898-6
    ISSN 0570-1783
    ISSN 0570-1783
    DOI 10.1016/j.aoas.2019.05.008
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  10. Article: A sulfated polyphenols-rich extract from

    Fahmi, Abdelgawad A / El Raey, Mohamed A / Ibrahim, Abeer Y / Abdelfattah, Mohamed A O / Abdelmageed, Abeer M / Sobeh, Mansour

    Saudi journal of biological sciences

    2021  Volume 28, Issue 5, Page(s) 3117–3125

    Abstract: Cancer is the second leading cause of mortality accounting for one in every six deaths globally. Plant secondary metabolites, among them polyphenols, represent an effective and much safer alternative approach to the currently available medications. In ... ...

    Abstract Cancer is the second leading cause of mortality accounting for one in every six deaths globally. Plant secondary metabolites, among them polyphenols, represent an effective and much safer alternative approach to the currently available medications. In this work, utilizing LC-MS/MS, we characterized the constituents of
    Language English
    Publishing date 2021-02-21
    Publishing country Saudi Arabia
    Document type Journal Article
    ZDB-ID 2515206-3
    ISSN 2213-7106 ; 1319-562X
    ISSN (online) 2213-7106
    ISSN 1319-562X
    DOI 10.1016/j.sjbs.2021.02.056
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