Sesquiterpene lactones; Damsin and neoambrosin suppress cytokine-mediated inflammation in complete Freund's adjuvant rat model via shutting Akt/ERK1/2/STAT3 signaling

Abdeldayem, Shymaa Ibrahim Ali; Khalil, Mohammed N.A.; Abdelrahman, Enas H.; El-Gohary, Hamida M.A.; Kamel, Ahmed S.

doi:10.1016/j.jep.2020.113407

Cited by 11 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, the identification of regulation of monocyte differentiation, regulation of myeloid leukocyte differentiation, macropinocytosis signaling, and Th1 and Th2 pathways suggested that the 21 key genes directly affect the differentiation and secretion of immune cells [27,28]. Moreover, it has been shown that the ERK1/2 signaling pathway and ephrin receptor signaling are involved in inflammatory responses in multiple organs and participate in processes such as development, activation, and migration of immune cells [28][29][30][31][32][33]. Furthermore, the 21 key module genes were obtained by WGCNA and differential expression analysis, and four genes (TRAF3IP2-AS1, PPARGC1B, CD4, and PDLIM5) were identified as the hub genes for CPB-induced inflammatory cytokine release in patients with congenital heart defects.…”

Section: Discussionmentioning

confidence: 99%

Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms

Liu

Zhang

2023

Disease Markers

View full text Add to dashboard Cite

Performing cardiopulmonary bypass (CPB) to reduce ischemic injury during surgery is a common approach to cardiac surgery. However, this procedure can lead to systemic inflammation and multiorgan dysfunction. Therefore, elucidating the molecular mechanisms of CPB-induced inflammatory cytokine release is essential as a critical first step in identifying new targets for therapeutic intervention. The GSE143780 dataset which is mRNA sequencing from total circulating leukocytes of the neonatorum was downloaded from the Gene Expression Omnibus (GEO) database. A total of 21 key module genes were obtained by analyzing the intersection of differentially expressed gene (DEG) and gene coexpression network analysis (WGCNA), and then, 4 genes (TRAF3IP2-AS1, PPARGC1B, CD4, and PDLIM5) were further confirmed after the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) screening and were used as hub genes for CPB-induced inflammatory cytokine release in patients with congenital heart defects. The enrichment analysis revealed 21 key module genes mainly related to the functions of developmental cell growth, regulation of monocyte differentiation, regulation of myeloid leukocyte differentiation, ERK1 and ERK2 cascade, volume-sensitive anion channel activity, and estrogen receptor binding. The result of gene set enrichment analysis (GSEA) showed that the hub genes were related to different physiological functions of cells. The ceRNA network established for hub genes includes 3 hub genes (PPARGC1B, CD4, and PDLIM5), 55 lncRNAs, and 34 miRNAs. In addition, 4 hub genes have 215 potential therapeutic agents. Finally, expression validation of the four hub genes revealed that they were all significantly low expressed in the surgical samples than before.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms

Liu

Zhang

2023

Disease Markers

View full text Add to dashboard Cite

show abstract

“…By contrast, phosphorylation at Ser9 is the inactive form. Previous studies have indicated that the phosphorylation at ser9 of GSK3B is decreased in mice with neuropathic pain versus untreated mice, and the inhibition of GSK3B activity attenuates neuropathic pain [ 32 – 34 ]. Here, we confirmed that the expression of GSK3B and GSK3B phosphorylation at Tyr216 (the active form) were up-regulated on days 1 and 7 after CFA injection (Fig.…”

Section: Discussionmentioning

confidence: 99%

Tau Accumulation in the Spinal Cord Contributes to Chronic Inflammatory Pain by Upregulation of IL-1β and BDNF

Zhang,

Chen,

Wang

et al. 2023

Neurosci. Bull.

View full text Add to dashboard Cite

Microtubule-associated protein Tau is responsible for the stabilization of neuronal microtubules under normal physiological conditions. Much attention has been focused on Tau’s contribution to cognition, but little research has explored its role in emotions such as pain, anxiety, and depression. In the current study, we found a significant increase in the levels of p-Tau (Thr231), total Tau, IL-1β, and brain-derived neurotrophic factor (BDNF) on day 7 after complete Freund's adjuvant (CFA) injection; they were present in the vast majority of neurons in the spinal dorsal horn. Microinjection of Mapt-shRNA recombinant adeno-associated virus into the spinal dorsal cord alleviated CFA-induced inflammatory pain and inhibited CFA-induced IL-1β and BDNF upregulation. Importantly, Tau overexpression was sufficient to induce hyperalgesia by increasing the expression of IL-1β and BDNF. Furthermore, the activation of glycogen synthase kinase 3 beta partly contributed to Tau accumulation. These findings suggest that Tau in the dorsal horn could be a promising target for chronic inflammatory pain therapy.

show abstract

“…This subgroup includes the lead compound helenalin being potently active but causing allergic reactions [5]. The subclass also includes analogues such as mexicanin I, damsin and neoambrosin [6][7][8]. Another important member of the group is britannin (BRT in Figure 2), initially isolated from the plant Inula britannica L. [9].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Bailly

2021

Biomedicines

View full text Add to dashboard Cite

Sesquiterpene lactones (SLs) are abundant in plants and display a large spectrum of bioactivities. The compound britannin (BRT), found in different Inula species, is a pseudoguaianolide-type SL equipped with a typical and highly reactive α-methylene-γ-lactone moiety. The bioproperties of BRT and related pseudoguaianolide SLs, including helenalin, gaillardin, bigelovin and others, have been reviewed. Marked anticancer activities of BRT have been evidenced in vitro and in vivo with different tumor models. Three main mechanisms are implicated: (i) interference with the NFκB/ROS pathway, a mechanism common to many other SL monomers and dimers; (ii) blockade of the Keap1-Nrf2 pathway, with a covalent binding to a cysteine residue of Keap1 via the reactive α-methylene unit of BRT; (iii) a modulation of the c-Myc/HIF-1α signaling axis leading to a downregulation of the PD-1/PD-L1 immune checkpoint and activation of cytotoxic T lymphocytes. The non-specific reactivity of the α-methylene-γ-lactone moiety with the sulfhydryl groups of proteins is discussed. Options to reduce or abolish this reactivity have been proposed. Emphasis is placed on the capacity of BRT to modulate the tumor microenvironment and the immune-modulatory action of the natural product. The present review recapitulates the anticancer effects of BRT, some central concerns with SLs and discusses the implication of the PD1/PD-L1 checkpoint in its antitumor action.

show abstract

Sesquiterpene lactones; Damsin and neoambrosin suppress cytokine-mediated inflammation in complete Freund's adjuvant rat model via shutting Akt/ERK1/2/STAT3 signaling

Cited by 11 publications

References 64 publications

Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms

Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms

Tau Accumulation in the Spinal Cord Contributes to Chronic Inflammatory Pain by Upregulation of IL-1β and BDNF

Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones

Contact Info

Product

Resources

About