Nigella sativa Extract and Thymoquinone Regulate Inflammatory Cytokine and TET-2 Expression in Endothelial Cells

Amartey, Jason; Gapper, Samuel; Hussein, Nurudeen; Morris, Keith; Withycombe, Cathryn

doi:10.2991/artres.k.191114.002

Cited by 8 publications

(6 citation statements)

References 30 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TQ also has decreased the expression of DNMT1, DNMT3A, and DNMT3B in Jurkat T-cell acute lymphoblastic leukemia cells [34]. TQ also has shown upregulation of TET2 in HECV human vascular endothelial cells [35]. In addition, curcumin treatment downregulated DNMT1 expression in MV4-11 AML cells [36].…”

Section: Discussionmentioning

confidence: 96%

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

et al. 2021

View full text Add to dashboard Cite

Epigenetic silencing of tumor suppressor genes (TSGs) plays an essential role in cancer pathogenesis, including acute myeloid leukemia (AML). All of SHP-1, SOCS-1, and SOCS-3 are TSGs that negatively regulate JAK/STAT signaling. Enhanced re-expression of TSGs through de-methylation represents a therapeutic target in several cancers. Thymoquinone (TQ) is a major component of Nigella sativa seeds with anticancer effects against several cancers. However, the effects of TQ on DNA methylation are not entirely understood. This study aimed to evaluate the ability of TQ to re-express SHP-1, SOCS-1, and SOCS-3 in MV4-11 AML cells through de-methylation. Cytotoxicity, apoptosis, and cell cycle assays were performed using WSTs-8 kit, Annexin V-FITC/PI apoptosis detection kit, and fluorometric-red cell cycle assay kit, respectively. The methylation of SHP-1, SOCS-1, and SOCS-3 was evaluated by pyrosequencing analysis. The expression of SHP-1, SOCS-1, SOCS-3, JAK2, STAT3, STAT5A, STAT5B, FLT3-ITD, DNMT1, DNMT3A, DNMT3B, TET2, and WT1 was assessed by RT-qPCR. The molecular docking of TQ to JAK2, STAT 3, and STAT5 was evaluated. The results revealed that TQ significantly inhibited the growth of MV4-11 cells and induced apoptosis in a dose- and time-dependent manner. Interestingly, the results showed that TQ binds the active pocket of JAK2, STAT3, and STAT5 to inhibit their enzymatic activity and significantly enhances the re-expression of SHP-1 and SOCS-3 through de-methylation. In conclusion, TQ curbs MV4-11 cells by inhibiting the enzymatic activity of JAK/STAT signaling through hypomethylation and re-expression of JAK/STAT negative regulators and could be a promising therapeutic candidate for AML patients.

show abstract

Section: Discussionmentioning

confidence: 96%

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Furthermore, TQ could reduce LPS-mediated inflammatory cytokine secretion, monocyte recruitment factors, and monocyte in human endothelial (HECV) cell lines. It could also downregulate the gene expression of VEGF and monocyte chemotactic protein-1 [ 129 ].…”

Section: Antioxidant and Anti-inflammatory Activities Of Tqmentioning

confidence: 99%

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

et al. 2021

View full text Add to dashboard Cite

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.

show abstract

“…Animal studies show TQ’s antiproliferative and anti-migratory effect on VSMCs through the AMPK/ Peroxisome proliferator-activated receptor gamma PPARγ/ Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) pathway ( 333 ). TQ reduces vascular inflammation by repressing the expression of vascular endothelial growth factor (VEGF) and monocyte chemo-attractant protein-1 (MCP-1), besides lowering levels of cytokines IL-6 and IL-8 in human vascular endothelial cells (HUVECs) ( 334 ). TQ has been shown to reverse endothelial dysfunction by increasing NO generation and bioavailability.…”

Section: The Role Of Herbal Medicine Formulations In Dm Treatmentmentioning

confidence: 99%

Mechanism of the antidiabetic action of Nigella sativa and Thymoquinone: a review

Shaukat,

Zaidi,

Anwar

et al. 2023

Front. Nutr.

View full text Add to dashboard Cite

IntroductionLong used in traditional medicine, Nigella sativa (NS; Ranunculaceae) has shown significant efficacy as an adjuvant therapy for diabetes mellitus (DM) management by improving glucose tolerance, decreasing hepatic gluconeogenesis, normalizing blood sugar and lipid imbalance, and stimulating insulin secretion from pancreatic cells. In this review, the pharmacological and pharmacokinetic properties of NS as a herbal diabetes medication are examined in depth, demonstrating how it counteracts oxidative stress and the onset and progression of DM.MethodsThis literature review drew on databases such as Google Scholar and PubMed and various gray literature sources using search terms like the etiology of diabetes, conventional versus herbal therapy, subclinical pharmacology, pharmacokinetics, physiology, behavior, and clinical outcomes.ResultsThe efficiency and safety of NS in diabetes, notably its thymoquinone (TQ) rich volatile oil, have drawn great attention from researchers in recent years; the specific therapeutic dose has eluded determination so far. TQ has anti-diabetic, anti-inflammatory, antioxidant, and immunomodulatory properties but has not proved druggable. DM’s intimate link with oxidative stress, makes NS therapy relevant since it is a potent antioxidant that energizes the cell’s endogenous arsenal of antioxidant enzymes. NS attenuates insulin resistance, enhances insulin signaling, suppresses cyclooxygenase-2, upregulates insulin-like growth factor-1, and prevents endothelial dysfunction in DM.ConclusionThe interaction of NS with mainstream drugs, gut microbiota, and probiotics opens new possibilities for innovative therapies. Despite its strong potential to treat DM, NS and TQ must be examined in more inclusive clinical studies targeting underrepresented patient populations.

show abstract

Nigella sativa Extract and Thymoquinone Regulate Inflammatory Cytokine and TET-2 Expression in Endothelial Cells

Cited by 8 publications

References 30 publications

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Mechanism of the antidiabetic action of Nigella sativa and Thymoquinone: a review

Contact Info

Product

Resources

About