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Article ; Online: Mentha pulegium

El-Gazar, Amira A / Emad, Ayat M / Ragab, Ghada M / Rasheed, Dalia M

2022 Volume 14, Issue 5

Abstract: Pregnant women usually turn to natural products to relieve pregnancy-related ailments which might pose health risks. ...

Abstract	Pregnant women usually turn to natural products to relieve pregnancy-related ailments which might pose health risks.
MeSH term(s)	Abortion, Induced ; Animals ; Chromatography, High Pressure Liquid ; Female ; Hormones ; Humans ; Lamiaceae ; Matrix Metalloproteinase 9 ; Mentha pulegium ; MicroRNAs ; Misoprostol ; Placenta ; Plant Extracts ; Pregnancy ; Rats ; Signal Transduction ; Spectrometry, Mass, Electrospray Ionization ; Tissue Inhibitor of Metalloproteinase-1
Chemical Substances	Hormones ; MIRN520 microRNA, human ; MicroRNAs ; Plant Extracts ; Tissue Inhibitor of Metalloproteinase-1 ; Misoprostol (0E43V0BB57) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2022-05-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins14050347
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Attenuative Effects of Fluoxetine and

Abu-Elfotuh, Karema / Ragab, Ghada M / Salahuddin, Ahmad / Jamil, Lubna / Abd Al Haleem, Ekram Nemr

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 21

Abstract: Background: Alzheimer's disease (AD) is a chronic neurological illness that causes considerable cognitive impairment. Hepatic and renal dysfunction may worsen AD by disrupting β-amyloid homeostasis at the periphery and by causing metabolic dysfunction. ... ...

Abstract	Background: Alzheimer's disease (AD) is a chronic neurological illness that causes considerable cognitive impairment. Hepatic and renal dysfunction may worsen AD by disrupting β-amyloid homeostasis at the periphery and by causing metabolic dysfunction. Wheatgrass (Triticum aestivum) has been shown to have antioxidant and anti-inflammatory properties. This work aims to study the effect of aluminum on neuronal cells, its consequences on the liver and kidneys, and the possible role of fluoxetine and wheatgrass juice in attenuating these pathological conditions. Method: Rats were divided into five groups. Control, AD (AlCl Conclusions: AlCl Conclusion: Fluoxetine and wheatgrass combination demonstrated a more significant neuroprotective impact in treating AD than fluoxetine alone and has protective effects on liver and kidney tissues.
MeSH term(s)	Aluminum Chloride/antagonists & inhibitors ; Alzheimer Disease/chemically induced ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Animals ; Fluoxetine/pharmacology ; Kidney/drug effects ; Kidney/pathology ; Liver/drug effects ; Liver/pathology ; Male ; Neuroprotective Agents/pharmacology ; Rats ; Rats, Wistar ; Triticum/chemistry
Chemical Substances	Neuroprotective Agents ; Fluoxetine (01K63SUP8D) ; Aluminum Chloride (3CYT62D3GA)
Language	English
Publishing date	2021-11-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26216752
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Article ; Online: Micro RNAs 26b, 20a inversely correlate with GSK-3 β/NF-κB/NLRP-3 pathway to highlight the additive promising effects of atorvastatin and quercetin in experimental induced arthritis.

Ibrahim, Sherihan Salaheldin Abdelhamid / Kandil, Lamia Said / Ragab, Ghada M / El-Sayyad, Shorouk M

International immunopharmacology

2021 Volume 99, Page(s) 108042

Abstract: Rheumatoid arthritis (RA) is an inflammatory disease with challenging therapeutic potential due to the implication of cross-talking intracellular pathways in the pathogenesis of the disease. This study aimed to evaluate the effects of the combination ... ...

Abstract	Rheumatoid arthritis (RA) is an inflammatory disease with challenging therapeutic potential due to the implication of cross-talking intracellular pathways in the pathogenesis of the disease. This study aimed to evaluate the effects of the combination therapy of atorvastatin and quercetin on glycogen synthase kinase-3 beta/ nuclear factor kappa-B/ nucleotide-binding oligomerization domain-like receptor family pyrin domain containing-3 or inflammasome (GSK-3β/NF-KB/NLRP-3) pathway as well as on microRNAs 26b and 20a (miR-26b, miR-20a) and to investigate the possible beneficial outcomes of the combination to offer a better treatment option than methotrexate (MTX) in adjuvant-induced arthritis (AIA). Assessment of arthritis progression, serum inflammatory, and oxidative parameters were done. The tibiotarsal tissue expression of the inflammatory parameters was evaluated. Western blot analysis was done to assess the expression level of the important members in the GSK-3β/NF-κB/NLRP-3 pathway. Furthermore, the expression level of both microRNAs and serum level of transaminases were determined. All treatments, especially the combination regimen, abated arthritis progression, the elevated serum level of inflammatory and oxidative stress parameters in arthritic rats. Moreover, They down-regulated the gene expression of the important members of the aforementioned signaling pathway, amended the tissue levels of inflammatory parameters and elevated the expression level of miR-26b and miR-20a. Finally, we concluded that the combination therapy modulated miR-26b and miR-20a as well as GSK-3β/NF-κB/NLRP-3 pathway, provided additive anti-inflammatory and anti-oxidant effects and offered an additional hepatoprotective effect as compared to untreated arthritic rats and MTX-treated groups, suggesting its promising role to be used as replacement therapy to MTX in RA.
MeSH term(s)	Alanine Transaminase/blood ; Animals ; Antirheumatic Agents/pharmacology ; Antirheumatic Agents/therapeutic use ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/metabolism ; Aspartate Aminotransferases/blood ; Atorvastatin/pharmacology ; Atorvastatin/therapeutic use ; CARD Signaling Adaptor Proteins/metabolism ; Carrier Proteins/blood ; Caspase 1/metabolism ; Cell Cycle Proteins/metabolism ; Correlation of Data ; Cytokines/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; I-kappa B Proteins/metabolism ; Male ; Malondialdehyde/blood ; Methotrexate/pharmacology ; Methotrexate/therapeutic use ; MicroRNAs/genetics ; MicroRNAs/metabolism ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Quercetin/pharmacology ; Quercetin/therapeutic use ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Rats
Chemical Substances	Antirheumatic Agents ; CARD Signaling Adaptor Proteins ; Carrier Proteins ; Cell Cycle Proteins ; Crp protein, rat ; Cytokines ; I kappa B beta protein ; I-kappa B Proteins ; MIRN20 microRNA, rat ; MIRN26 microRNA, rat ; MicroRNAs ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, rat ; Pycard protein, rat ; TXNIP protein, rat ; Malondialdehyde (4Y8F71G49Q) ; Quercetin (9IKM0I5T1E) ; Atorvastatin (A0JWA85V8F) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, rat (EC 2.7.11.1) ; Caspase 1 (EC 3.4.22.36) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-08-13
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2021.108042
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Article ; Online: Gastroprotective potential of red onion (Allium cepa L.) peel in ethanol-induced gastric injury in rats: Involvement of Nrf2/HO-1 and HMGB-1/NF-κB trajectories.

Ali, Nermeen B / Abdelhamid Ibrahim, Sherihan Salaheldin / Alsherbiny, Muhammad A / Sheta, Eman / El-Shiekh, Riham A / Ashour, Rehab M / El-Gazar, Amira A / Ragab, Ghada M / El-Gayed, Sabah H / Li, Chun Guang / Abdel-Sattar, Essam

Journal of ethnopharmacology

2023 Volume 319, Issue Pt 1, Page(s) 117115

Abstract: Ethnopharmacological relevance: The utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and ... ...

Abstract	Ethnopharmacological relevance: The utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and antioxidant potential in the treatment of various ailments, including gastric ulcers. Aim of the study: This study investigated the gastroprotective potential of red onion peel extract and its fractions in a rat model of ethanol-induced gastric ulcer. Moreover, their phytochemical profiles were compared to identify the active metabolites. Materials and methods: Mass spectrometry-based metabolomics and chemometrics were performed for phytochemical analysis. Ethanol-induced gastric ulcer model was used to assess the gastroprotective activity. Nine groups of rats were allocated as follows: Group 1 was the normal control; Group 2 rats were used as a positive control/model and received 1 mL of absolute ethanol; and Group 3 rats were treated with famotidine at a dose of 20 mg/kg orally. Group 4 and 5 rats were treated with total acidified ethanolic extract (T1, T2). Group 6 and 7 rats were treated with anthocyanins-rich fractions (P1, P2). Groups 8 and 9 were the flavonoids-rich fraction (S1, S2) treatment. Prior to scarification, the ulcer index in mm was obtained from gastric tissues photographed beside a ruler with further analysis using ImageJ software. Results: Seventy key major and discriminatory metabolites were identified including flavonoids, anthocyanins, phenolic acids, and miscellaneous compounds. The examined extract and its fractions significantly reduced the ulcer index and inflammatory cytokines via downregulating HMGB-1/NF-κB. Also, they augmented the expression of Nrf2/HO-1 and reduced NOX1/4 mRNA expression. Moreover, there was a significant reduction in the oxidative stress and apoptotic biomarkers as well as a noticeable enhancement in histopathological changes of the stomach tissues. Conclusion: Red onion peels have a promising dose dependent gastroprotective potential in alcohol-induced ulcers via modulating Nrf2/HO-1 and HMGB-1/NF-κB trajectories. This highlights the potential of red onion peels in treating gastric ulcers.
MeSH term(s)	Rats ; Animals ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy ; Stomach Ulcer/pathology ; Ethanol/therapeutic use ; Onions ; NF-kappa B/metabolism ; Ulcer/drug therapy ; Anthocyanins ; NF-E2-Related Factor 2/metabolism ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Plant Extracts/chemistry ; Anti-Ulcer Agents/pharmacology ; Anti-Ulcer Agents/therapeutic use ; Anti-Ulcer Agents/chemistry ; Flavonoids/therapeutic use ; Phytochemicals/adverse effects ; HMGB Proteins/metabolism ; Gastric Mucosa/pathology
Chemical Substances	Ethanol (3K9958V90M) ; NF-kappa B ; Anthocyanins ; NF-E2-Related Factor 2 ; Plant Extracts ; Anti-Ulcer Agents ; Flavonoids ; Phytochemicals ; HMGB Proteins
Language	English
Publishing date	2023-09-01
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.117115
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Article ; Online: Metformin and omega-3 fish oil elicit anti-inflammatory effects via modulation of some dysregulated micro RNAs expression and signaling pathways in experimental induced arthritis.

El-Sayyad, Shorouk M / Ali, Mennatallah A / Kandil, Lamia S / Ragab, Ghada M / Abdelhamid Ibrahim, Sherihan S

International immunopharmacology

2021 Volume 92, Page(s) 107362

Abstract: Objective: Rheumatoid arthritis is a progressive inflammatory disease with multiple dysfunctional intracellular signaling pathways that necessitate new approaches for its management. Hence, the study aimed to inspect the ability of the combination ... ...

Abstract	Objective: Rheumatoid arthritis is a progressive inflammatory disease with multiple dysfunctional intracellular signaling pathways that necessitate new approaches for its management. Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate. Methods: Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with metformin (200 mg/kg/day) and/or omega-3 (300 mg/kg/day) or intraperitoneally with methotrexate (2 mg/kg/week) for 4 weeks. Results and conclusion: All drug treatments amended the arthrogram score and hind paw swelling as well as decreased serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. On the molecular level, all therapies activated phospho-5'adenosine monophosphate-activated protein kinase (p-AMPK) and protein phosphatase 2A (PP2A), while they inhibited phospho-mammalian target of rapamycin (p-mTOR), phospho-signal transducers and activators of transcription (p-STAT3), nuclear factor (NF)-κB p65 subunit, phosho38 mitogen-activated protein kinase (p38 MAPK) and phospho- c-Jun N-terminal kinase (p-JNK). In addition, they decreased the elevated expression level of miRNA-155, 146a and increased the expression level of miRNA-34 and they decreased the expression level of retinoic acid receptor related orphan receptor γT (RORγT) and increased that of fork head box P3 (FOXP3), correcting Th17/Treg cells balance. On most of the aforementioned parameters, the effect of the combination therapy was comparable to that of methotrexate, emphasizing that this combination possesses better additive anti-inflammatory effect than either drug when used alone. In addition, the combination was capable of normalizing the serum transaminases levels as compared to untreated group offering hepatoprotective effect and suggesting the possibility of its use as a replacement therapeutic strategy for MTX in rheumatoid arthritis.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antimetabolites, Antineoplastic/toxicity ; Arthritis, Experimental/chemically induced ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/immunology ; Arthritis, Experimental/metabolism ; Disease Models, Animal ; Drug Therapy, Combination ; Fish Oils/pharmacology ; Gene Expression Regulation/drug effects ; Hypoglycemic Agents/pharmacology ; Interleukin-1beta/blood ; Male ; Metformin/pharmacology ; Methotrexate/toxicity ; MicroRNAs/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; T-Lymphocytes, Regulatory/metabolism ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Anti-Inflammatory Agents ; Antimetabolites, Antineoplastic ; Fish Oils ; Hypoglycemic Agents ; IL1B protein, rat ; Interleukin-1beta ; MicroRNAs ; Tumor Necrosis Factor-alpha ; Metformin (9100L32L2N) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-01-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2020.107362
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Article ; Online: Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues.

Nazeam, Jilan A / Ragab, Ghada M / El-Gazar, Amira A / El-Mancy, Shereen S / Jamil, Lina / Fayez, Sahar M

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 18

Abstract: Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent ... ...

Abstract	Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes' pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an
MeSH term(s)	Acne Vulgaris/drug therapy ; Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Behavior, Animal/drug effects ; Biofilms/drug effects ; Cues ; Forkhead Transcription Factors/metabolism ; Insulin-Like Growth Factor I/metabolism ; Interleukin-6/metabolism ; NF-kappa B/metabolism ; Nanogels/chemistry ; Nanogels/therapeutic use ; PPAR gamma/metabolism ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacology ; Polyethylene Glycols/therapeutic use ; Polyethyleneimine/chemistry ; Polyethyleneimine/pharmacology ; Polyethyleneimine/therapeutic use ; Rats ; Skin/drug effects ; Skin/metabolism ; Syzygium/chemistry ; Thymus Plant/chemistry ; Toll-Like Receptor 2/metabolism ; Transforming Growth Factor beta/metabolism ; Wnt Proteins/metabolism
Chemical Substances	Anti-Bacterial Agents ; Anti-Inflammatory Agents ; Forkhead Transcription Factors ; Interleukin-6 ; NF-kappa B ; Nanogels ; PPAR gamma ; Plant Extracts ; Toll-Like Receptor 2 ; Transforming Growth Factor beta ; Wnt Proteins ; polyethylene glycol polyethyleneimine nanogel ; Polyethylene Glycols (3WJQ0SDW1A) ; Insulin-Like Growth Factor I (67763-96-6) ; Polyethyleneimine (9002-98-6)
Language	English
Publishing date	2021-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26185608
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Article: Unlocking the Power of Onion Peel Extracts: Antimicrobial and Anti-Inflammatory Effects Improve Wound Healing through Repressing Notch-1/NLRP3/Caspase-1 Signaling.

Mounir, Rafik / Alshareef, Walaa A / El Gebaly, Eman A / El-Haddad, Alaadin E / Ahmed, Abdallah M Said / Mohamed, Osama G / Enan, Eman T / Mosallam, Shaimaa / Tripathi, Ashootosh / Selim, Heba Mohammed Refat M / Bukhari, Sarah I / Alfaraj, Rihaf / Ragab, Ghada M / El-Gazar, Amira A / El-Emam, Soad Z

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 10

Abstract: Onion peels are often discarded, representing an unlimited amount of food by-products; however, they are a valuable source of bioactive phenolics. Thus, we utilized UPLC-MS/MS to analyze the metabolomic profiles of red (RO) and yellow (YO) onion peel ... ...

Abstract	Onion peels are often discarded, representing an unlimited amount of food by-products; however, they are a valuable source of bioactive phenolics. Thus, we utilized UPLC-MS/MS to analyze the metabolomic profiles of red (RO) and yellow (YO) onion peel extracts. The cytotoxic (SRB assay), anti-inflammatory (Griess assay), and antimicrobial (sensitivity test, MIC, antibiofilm, and SP-SDS tests) properties were assessed in vitro. Additionally, histological analysis, immunohistochemistry, and ELISA tests were conducted to investigate the healing potential in excisional skin wound injury and
Language	English
Publishing date	2023-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16101379
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Article: Possible Implication of Nrf2, PPAR-γ and MAPKs Signaling in the Protective Role of Mangiferin against Renal Ischemia/Reperfusion in Rats.

Gendy, Abdallah M / El-Gazar, Amira A / Ragab, Ghada M / Al-Mokaddem, Asmaa K / El-Haddad, Alaadin E / Selim, Heba Mohammed Refat M / Yousef, Einas Mohamed / Hamed, Najat O / Ibrahim, Sherihan Salaheldin Abdelhamid

Pharmaceuticals (Basel, Switzerland)

2022 Volume 16, Issue 1

Abstract: Mangiferin (Mang) is a known glucosylxanthone that has proven its shielding effect against ischemia/reperfusion (Is/R). However, its full underlying mechanistic perspective against renal Is/R induced lesions is not fully revealed. Consequently, the ... ...

Abstract	Mangiferin (Mang) is a known glucosylxanthone that has proven its shielding effect against ischemia/reperfusion (Is/R). However, its full underlying mechanistic perspective against renal Is/R induced lesions is not fully revealed. Consequently, the purpose of this study is to track further non-investigated modulatory signals of Mang against the renal Is/R model involving nuclear factor erythroid 2-related factor (Nrf)2/heme oxygenase (HO)-1, peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling. To ratify our aim, Mang was administrated (20 mg/kg, i.p for seven days) before the induction of bilateral Is/R. Mechanistic maneuver revealed that Mang balanced oxidative state via increasing the expression of the antioxidant Nrf2/HO-1 cue with subsequent enhancement of GSH besides MDA lessening. Additionally, Mang enhanced PPAR-γ mRNA expression and declined
Language	English
Publishing date	2022-12-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16010006
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Article ; Online: Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF.

Abd El-Aal, Sarah A / AbdElrahman, Mohamed / Reda, Ahmed M / Afify, Hassan / Ragab, Ghada M / El-Gazar, Amira A / Ibrahim, Sherihan Salaheldin Abdelhamid

Neurotoxicology

2022 Volume 92, Page(s) 77–90

Abstract: The cognitive and behavioral decline observed in cancer survivors who underwent doxorubicin (DOX)-based treatment raises the need for therapeutic interventions to counteract these complications. Galangin (GAL) is a flavonoid-based phytochemical with ... ...

Abstract	The cognitive and behavioral decline observed in cancer survivors who underwent doxorubicin (DOX)-based treatment raises the need for therapeutic interventions to counteract these complications. Galangin (GAL) is a flavonoid-based phytochemical with pronounced protective effects in various neurological disorders. However, its impact on DOX-provoked neurotoxicity has not been clarified. Hence, the current investigation aimed to explore the ability of GAL to ameliorate DOX-provoked chemo-brain in rats. DOX (2 mg/kg, once/week, i.p.) and GAL (50 mg/kg, 5 times/week., via gavage) were administered for four successive weeks. The MWM and EPM tests were used to evaluate memory disruption and anxiety-like behavior, respectively. Meanwhile, targeted biochemical markers and molecular signals were examined by the aid of ELISA, Western blotting, and immune-histochemistry. In contrast to DOX-impaired rats, GAL effectively preserved hippocampal neurons, improved cognitive/behavioral functions, and enhanced the expression of the cell repair/growth index, BDNF. The antioxidant feature of GAL was confirmed by the amelioration of MDA, NO and NOX-1, along with restoring the Nrf-2/HO-1/GSH cue. In addition, GAL displayed marked anti-inflammatory properties as verified by the suppression of the HMGB1/TLR4 nexus and p-NF-κB p65 to inhibit TNF-α, IL-6, IL-1β, and iNOS. This inhibitory impact extended to entail astrocyte activation, as evidenced by the diminution of GFAP. These beneficial effects were associated with a notable reduction in p-p38
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Biomarkers/metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/prevention & control ; Doxorubicin/toxicity ; Flavonoids/pharmacology ; Flavonoids/therapeutic use ; GA-Binding Protein Transcription Factor/metabolism ; HMGB1 Protein/metabolism ; HMGB1 Protein/pharmacology ; HMGB1 Protein/therapeutic use ; Interleukin-6/metabolism ; NF-kappa B/metabolism ; Oxidative Stress ; Protein Kinases ; Rats ; Signal Transduction ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Biomarkers ; Brain-Derived Neurotrophic Factor ; Flavonoids ; GA-Binding Protein Transcription Factor ; HMGB1 Protein ; Interleukin-6 ; NF-kappa B ; Tlr4 protein, rat ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; galangin (142FWE6ECS) ; Doxorubicin (80168379AG) ; MLKL protein, rat (EC 2.7.-) ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2022-07-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	800820-6
ISSN	1872-9711 ; 0161-813X
ISSN (online)	1872-9711
ISSN	0161-813X
DOI	10.1016/j.neuro.2022.07.005
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Article ; Online: Enhanced Wound Healing Potential of Spirulina platensis Nanophytosomes: Metabolomic Profiling, Molecular Networking, and Modulation of HMGB-1 in an Excisional Wound Rat Model

Refai, Hanan / El-Gazar, Amira A. / Ragab, Ghada M. / Hassan, Doaa H. / Ahmed, Omar S. / Hussein, Rehab A. / Shabana, Samah / Waffo-Téguo, Pierre / Valls i Grau, Josep / Al-Mokaddem, Asmaa K. / Selim, Heba Mohammed Refat M. / Yousef, Einas Mohamed / Ali, Sahar K. / Salman, Ahmed / Abo-Zalam, Hagar B. / Albash, Rofida

Mar Drugs. 2023 Feb. 24, v. 21, no. 3

2023

Abstract: Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina ... ...

Abstract	Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimum physicochemical characteristics regarding particle size (598.40 ± 9.68 nm), zeta potential (−19.8 ± 0.49 mV), entrapment efficiency (62.76 ± 1.75%), and Q6h (74.00 ± 1.90%). It was selected to prepare an HPMC gel (SPNP-gel). Through metabolomic profiling of the algal extract, thirteen compounds were identified. Molecular docking of the identified compounds on the active site of the HMGB-1 protein revealed that 12,13-DiHome had the highest docking score of −7.130 kcal/mol. SPNP-gel showed higher wound closure potential and enhanced histopathological alterations as compared to standard (MEBO® ointment) and S. platensis gel in wounded Sprague-Dawley rats. Collectively, NPS promoted the wound healing process by enhancing the autophagy process (LC3B/Beclin-1) and the NRF-2/HO-1antioxidant pathway and halting the inflammatory (TNF-, NF-κB, TlR-4 and VEGF), apoptotic processes (AIF, Caspase-3), and the downregulation of HGMB-1 protein expression. The present study’s findings suggest that the topical application of SPNP-gel possesses a potential therapeutic effect in excisional wound healing, chiefly by downregulating HGMB-1 protein expression.
Keywords	Arthrospira platensis ; active sites ; algae ; animal models ; apoptosis ; autophagy ; caspase-3 ; gels ; histopathology ; metabolomics ; particle size ; protein synthesis ; topical application ; zeta potential
Language	English
Dates of publication	2023-0224
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2175190-0
ISSN	1660-3397
ISSN	1660-3397
DOI	10.3390/md21030149
Database	NAL-Catalogue (AGRICOLA)

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