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Article ; Online: Determination of benchmark doses for linear furanocoumarin consumption associated with inhibition of cytochrome P450 1A2 isoenzyme activity in healthy human adults.

Alehaideb, Zeyad / Matou-Nasri, Sabine

2021 Volume 8, Page(s) 1437–1444

Abstract: Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins ( ...

Abstract	Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins (
Language	English
Publishing date	2021-07-22
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2805786-7
ISSN	2214-7500 ; 2214-7500
ISSN (online)	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2021.07.013
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Article: Determination of benchmark doses for linear furanocoumarin consumption associated with inhibition of cytochrome P450 1A2 isoenzyme activity in healthy human adults

Alehaideb, Zeyad / Matou-Nasri, Sabine

Toxicology reports. 2021, v. 8

2021

Abstract: Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins (i.e., 8-methoxypsoralen, 5-methoxypsoralen, and isopimpinellin) are inhibitors of cytochrome ... ...

Abstract	Millions of individuals globally consume traditional herbal medicines (THMs), which contain abundant amounts of linear furanocoumarins. Linear furanocoumarins (i.e., 8-methoxypsoralen, 5-methoxypsoralen, and isopimpinellin) are inhibitors of cytochrome P450 (CYP) isoenzymes including 1A2, a major enzyme involved in drug metabolism and carcinogen bioactivation. Despite the high consumption of furanocoumarin-containing THMs, no studies have measured the furanocoumarin consumption level that triggers an inhibition to CYP1A2 activity in humans. The first objective was to verify if the potencies of the three furanocoumarins are additive towards the inhibition of CYP1A2 activity in vitro using concentration-addition and whole-mixture chemical-mixture-assessment models. A second objective was to determine the benchmark dose (BMD) with the mixtures of furanocoumarin oral doses, expressed as 8-MOP equivalents, and to assess the in vivo CYP1A2 activity, expressed as inhibition percentages. The in vitro results indicated that the three furanocoumarin inhibitory potencies were additive in the THM extracts, validating the use of the concentration-addition model in total furanocoumarin dose-equivalent calculations. Using the USEPA BMD software, the BMD was 18.9 μg 8-MOP equivalent/kg body weight. This information is crucial for furanocoumarin-related health-assessment studies and the regulation of THMs. Further studies should be performed for the remaining major metabolic enzymes to complete the safety profile of furanocoumarin-containing THMs and to provide accurate warning labelling.
Keywords	United States Environmental Protection Agency ; bergapten ; body weight ; carcinogens ; computer software ; cytochrome P-450 ; enzymes ; humans ; isozymes ; methoxsalen ; models ; pharmacokinetics ; toxicology
Language	English
Size	p. 1437-1444.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2805786-7
ISSN	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2021.07.013
Database	NAL-Catalogue (AGRICOLA)

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Article: Updates on Triple-Negative Breast Cancer in Type 2 Diabetes Mellitus Patients: From Risk Factors to Diagnosis, Biomarkers and Therapy.

Matou-Nasri, Sabine / Aldawood, Maram / Alanazi, Fatimah / Khan, Abdul Latif

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 14

Abstract: Triple-negative breast cancer (TNBC) is usually the most malignant and aggressive mammary epithelial tumor characterized by the lack of expression for estrogen receptors and progesterone receptors, and the absence of epidermal growth factor receptor (HER) ...

Abstract	Triple-negative breast cancer (TNBC) is usually the most malignant and aggressive mammary epithelial tumor characterized by the lack of expression for estrogen receptors and progesterone receptors, and the absence of epidermal growth factor receptor (HER)2 amplification. Corresponding to 15-20% of all breast cancers and well-known by its poor clinical outcome, this negative receptor expression deprives TNBC from targeted therapy and makes its management therapeutically challenging. Type 2 diabetes mellitus (T2DM) is the most common ageing metabolic disorder due to insulin deficiency or resistance resulting in hyperglycemia, hyperinsulinemia, and hyperlipidemia. Due to metabolic and hormonal imbalances, there are many interplays between both chronic disorders leading to increased risk of breast cancer, especially TNBC, diagnosed in T2DM patients. The purpose of this review is to provide up-to-date information related to epidemiology and clinicopathological features, risk factors, diagnosis, biomarkers, and current therapy/clinical trials for TNBC patients with T2DM compared to non-diabetic counterparts. Thus, in-depth investigation of the diabetic complications on TNBC onset, development, and progression and the discovery of biomarkers would improve TNBC management through early diagnosis, tailoring therapy for a better outcome of T2DM patients diagnosed with TNBC.
Language	English
Publishing date	2023-07-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13142390
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Article: Pharmacological p38 MAPK inhibitor SB203580 enhances AML stem cell line KG1a chemosensitivity to daunorubicin by promoting late apoptosis, cell growth arrest in S-phase, and miR-328-3p upregulation.

Bahattab, Sara / Assiri, Ali / Alhaidan, Yazeid / Trivilegio, Thadeo / AlRoshody, Rehab / Huwaizi, Sarah / Almuzzaini, Bader / Alamro, Abir / Abudawood, Manal / Alehaideb, Zeyad / Matou-Nasri, Sabine

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society

2024 Volume 32, Issue 6, Page(s) 102055

Abstract: Acute myeloid leukaemia (AML) is characterized by uncontrolled proliferation of myeloid progenitor cells and impaired maturation, leading to immature cell accumulation in the bone marrow and bloodstream, resulting in hematopoietic dysfunction. ... ...

Abstract	Acute myeloid leukaemia (AML) is characterized by uncontrolled proliferation of myeloid progenitor cells and impaired maturation, leading to immature cell accumulation in the bone marrow and bloodstream, resulting in hematopoietic dysfunction. Chemoresistance, hyperactivity of survival pathways, and miRNA alteration are major factors contributing to treatment failure and poor outcomes in AML patients. This study aimed to investigate the impact of the pharmacological p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 on the chemoresistance potential of AML stem cell line KG1a to the therapeutic drug daunorubicin (DNR). KG1a and chemosensitive leukemic HL60 cells were treated with increasing concentrations of DNR. Cell Titer-Glo®, flow cytometry, phosphokinase and protein arrays, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were employed for assessment of cell viability, half-maximal inhibitory concentration (IC
Language	English
Publishing date	2024-03-30
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	1378024-4
ISSN	1319-0164
ISSN	1319-0164
DOI	10.1016/j.jsps.2024.102055
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Article ; Online: SARS-CoV-2 modulates inflammatory responses of alveolar epithelial type II cells

Al-Qahtani, Ahmed A / Pantazi, Ioanna / Alhamlan, Fatimah S / Alothaid, Hani / Matou-Nasri, Sabine / Sourvinos, George / Vergadi, Eleni / Tsatsanis, Christos

Frontiers in immunology

2022 Volume 13, Page(s) 1020624

Abstract: Background: SARS-CoV-2 infects through the respiratory route and triggers inflammatory response by affecting multiple cell types including type II alveolar epithelial cells. SARS-CoV-2 triggers signals : Aim: Aim of the present study was to ... ...

Abstract	Background: SARS-CoV-2 infects through the respiratory route and triggers inflammatory response by affecting multiple cell types including type II alveolar epithelial cells. SARS-CoV-2 triggers signals Aim: Aim of the present study was to investigate the effect of SARS-CoV2 on type II alveolar epithelial cells, focusing on signals initiated by its S protein and their impact on the expression of inflammatory mediators. Results: For this purpose A549 alveolar type II epithelial cells were exposed to SARS CoV2 S recombinant protein and the expression of inflammatory mediators was measured. The results showed that SARS-CoV-2 S protein decreased the expression and secretion of IL8, IL6 and TNFα, 6 hours following stimulation, while it had no effect on IFNα, CXCL5 and PAI-1 expression. We further examined whether SARS-CoV-2 S protein, when combined with TLR2 signals, which are also triggered by SARS-CoV2 and its envelope protein, exerts a different effect in type II alveolar epithelial cells. Simultaneous treatment of A549 cells with SARS-CoV-2 S protein and the TLR2 ligand PAM3csk4 decreased secretion of IL8, IL6 and TNFα, while it significantly increased IFNα, CXCL5 and PAI-1 mRNA expression. To investigate the molecular pathway through which SARS-CoV-2 S protein exerted this immunomodulatory action in alveolar epithelial cells, we measured the induction of MAPK/ERK and PI3K/AKT pathways and found that SARS-CoV-2 S protein induced the activation of the serine threonine kinase AKT. Treatment with the Akt inhibitor MK-2206, abolished the inhibitory effect of SARS-CoV-2 S protein on IL8, IL6 and TNFα expression, suggesting that SARS-CoV-2 S protein mediated its action Conclusion: The findings of our study, showed that SARS-CoV-2 S protein suppressed inflammatory responses in alveolar epithelial type II cells at early stages of infection through activation of the PI3K/AKT pathway. Thus, our results suggest that at early stages SARS-CoV-2 S protein signals inhibit immune responses to the virus allowing it to propagate the infection while in combination with TLR2 signals enhances PAI-1 expression, potentially affecting the local coagulation cascade.
MeSH term(s)	Humans ; Alveolar Epithelial Cells/metabolism ; SARS-CoV-2 ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt ; Tumor Necrosis Factor-alpha ; RNA, Viral ; Plasminogen Activator Inhibitor 1 ; Interleukin-6 ; Interleukin-8 ; Toll-Like Receptor 2 ; COVID-19
Chemical Substances	spike protein, SARS-CoV-2 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Tumor Necrosis Factor-alpha ; RNA, Viral ; Plasminogen Activator Inhibitor 1 ; Interleukin-6 ; Interleukin-8 ; Toll-Like Receptor 2
Language	English
Publishing date	2022-10-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1020624
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Article: Stimulatory effects of

Alghamdi, Khalid / Alehaideb, Zeyad / Kumar, Ashok / Al-Eidi, Hamad / Alghamdi, Sahar S / Suliman, Rasha / Ali, Rizwan / Almourfi, Feras / Alghamdi, Saleh M / Boudjelal, Mohamed / Matou-Nasri, Sabine

Frontiers in pharmacology

2023 Volume 14, Page(s) 1169812

Abstract: There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In ...

Abstract	There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts,
Language	English
Publishing date	2023-04-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1169812
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Article ; Online: Herbal melanin modulates PGE2 and IL-6 gastroprotective markers through COX-2 and TLR4 signaling in the gastric cancer cell line AGS.

El-Obeid, Adila / Maashi, Yahya / AlRoshody, Rehab / Alatar, Ghada / Aljudayi, Modhi / Al-Eidi, Hamad / AlGaith, Nouf / Khan, Altaf Husain / Hassib, Adil / Matou-Nasri, Sabine

BMC complementary medicine and therapies

2023 Volume 23, Issue 1, Page(s) 305

Abstract: We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed ... ...

Abstract	We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) and toll-like receptor 4 (TLR4)-mediated interleukin-6 (IL-6) production and secretion play major roles in gastric mucosal protection. In the current study, the human gastric carcinoma epithelial cell line AGS was used as a model to investigate the effect of HM on TLR4, COX-2, glycoprotein mucin 4 protein and gene expression using immuno-cyto-fluorescence staining, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gastroprotective markers PGE2 and IL-6 production and secretion were also assessed using an enzyme-linked immunosorbent assay (ELISA). Bacterial lipopolysaccharides (LPS), well-known inducers of TLR4, COX-2, PGE2 and IL-6 expression, were used as a positive control. We showed that HM upregulated its main receptor TLR4 gene and protein expression in AGS cells. HM increased, in a dose- and time-dependent manner, the secretion of PGE2 and the expression of COX-2 mRNA and protein, which was detected in the nucleus, cytoplasm and predominantly at the intercellular junctions of the AGS cells. In addition, HM enhanced IL-6 production and secretion, and upregulated the mucin 4 gene expression, the hallmarks of gastroprotection. To check whether HM-induced PGE2 and IL-6 through TLR4 signaling and COX-2 generated, AGS cells were pre-treated with a TLR4 signaling inhibitor TAK242 and the COX-2 inhibitor NS-398. A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.
MeSH term(s)	Humans ; Animals ; Rats ; Stomach Neoplasms ; Melanins ; Cyclooxygenase 2 ; Dinoprostone ; Toll-Like Receptor 4 ; Interleukin-6 ; Mucin-4
Chemical Substances	ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate ; Melanins ; N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (123653-11-2) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M) ; Toll-Like Receptor 4 ; Interleukin-6 ; Mucin-4 ; TLR4 protein, human
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-023-04124-3
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Article ; Online: Herbal melanin induces interleukin-1β secretion and production by human THP-1 monocytes via Toll-like receptor 2 and p38 MAPK activation.

El-Obeid, Adila / Yahya, Wesam Bin / Almuzzaini, Bader / Tuwaijri, Abeer Al / Najdi, Maria / Hassib, Adil / Matou-Nasri, Sabine

Experimental and therapeutic medicine

2021 Volume 22, Issue 4, Page(s) 1081

Abstract: Herbal melanin (HM), extracted ... ...

Abstract	Herbal melanin (HM), extracted from
Language	English
Publishing date	2021-07-29
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2021.10515
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Article ; Online: SARS-CoV-2/ACE2 Interaction Suppresses IRAK-M Expression and Promotes Pro-Inflammatory Cytokine Production in Macrophages.

Pantazi, Ioanna / Al-Qahtani, Ahmed A / Alhamlan, Fatimah S / Alothaid, Hani / Matou-Nasri, Sabine / Sourvinos, George / Vergadi, Eleni / Tsatsanis, Christos

Frontiers in immunology

2021 Volume 12, Page(s) 683800

Abstract: The major cause of death in SARS-CoV-2 infected patients is due to de-regulation of the innate immune system and development of cytokine storm. SARS-CoV-2 infects multiple cell types in the lung, including macrophages, by engagement of its spike (S) ... ...

Abstract	The major cause of death in SARS-CoV-2 infected patients is due to de-regulation of the innate immune system and development of cytokine storm. SARS-CoV-2 infects multiple cell types in the lung, including macrophages, by engagement of its spike (S) protein on angiotensin converting enzyme 2 (ACE2) receptor. ACE2 receptor initiates signals in macrophages that modulate their activation, including production of cytokines and chemokines. IL-1R-associated kinase (IRAK)-M is a central regulator of inflammatory responses regulating the magnitude of TLR responsiveness. Aim of the work was to investigate whether SARS-CoV-2 S protein-initiated signals modulate pro-inflammatory cytokine production in macrophages. For this purpose, we treated PMA-differentiated THP-1 human macrophages with SARS-CoV-2 S protein and measured the induction of inflammatory mediators including IL6, TNFα, IL8, CXCL5, and MIP1a. The results showed that SARS-CoV-2 S protein induced IL6, MIP1a and TNFα mRNA expression, while it had no effect on IL8 and CXCL5 mRNA levels. We further examined whether SARS-CoV-2 S protein altered the responsiveness of macrophages to TLR signals. Treatment of LPS-activated macrophages with SARS-CoV-2 S protein augmented IL6 and MIP1a mRNA, an effect that was evident at the protein level only for IL6. Similarly, treatment of PAM3csk4 stimulated macrophages with SARS-CoV-2 S protein resulted in increased mRNA of IL6, while TNFα and MIP1a were unaffected. The results were confirmed in primary human peripheral monocytic cells (PBMCs) and isolated CD14+ monocytes. Macrophage responsiveness to TLR ligands is regulated by IRAK-M, an inactive IRAK kinase isoform. Indeed, we found that SARS-CoV-2 S protein suppressed IRAK-M mRNA and protein expression both in THP1 macrophages and primary human PBMCs and CD14+ monocytes. Engagement of SARS-CoV-2 S protein with ACE2 results in internalization of ACE2 and suppression of its activity. Activation of ACE2 has been previously shown to induce anti-inflammatory responses in macrophages. Treatment of macrophages with the ACE2 activator DIZE suppressed the pro-inflammatory action of SARS-CoV-2. Our results demonstrated that SARS-CoV-2/ACE2 interaction rendered macrophages hyper-responsive to TLR signals, suppressed IRAK-M and promoted pro-inflammatory cytokine expression. Thus, activation of ACE2 may be a potential anti-inflammatory therapeutic strategy to eliminate the development of cytokine storm observed in COVID-19 patients.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/immunology ; Cytokine Release Syndrome/immunology ; Gene Expression Regulation ; Humans ; Immunity, Innate ; Inflammation Mediators/metabolism ; Interleukin-1 Receptor-Associated Kinases/genetics ; Interleukin-1 Receptor-Associated Kinases/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Macrophages/virology ; Protein Binding ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/metabolism ; THP-1 Cells ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Inflammation Mediators ; Interleukin-6 ; Lipopolysaccharides ; MAPKAP1 protein, human ; Spike Glycoprotein, Coronavirus ; Tumor Necrosis Factor-alpha ; spike protein, SARS-CoV-2 ; IRAK3 protein, human (EC 2.7.11.1) ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-06-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.683800
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Article: Commiphora myrrha

Alehaideb, Zeyad / Alatar, Ghada / Nehdi, Atef / Albaz, Abeer / Al-Eidi, Hamad / Almutairi, Mansour / Hawsa, Esraa / Alshuail, Nora / Matou-Nasri, Sabine

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society

2021 Volume 29, Issue 5, Page(s) 361–368

Abstract: Commiphora ... ...

Abstract	Commiphora myrrha
Language	English
Publishing date	2021-04-01
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	1378024-4
ISSN	1319-0164
ISSN	1319-0164
DOI	10.1016/j.jsps.2021.03.002
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Zs.A 4758: Show issues

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ab Jg. 2022: Lesesaal (EG)

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