Triptolide induces apoptosis of glioma cells by inhibiting NF-κB activation during oxidative stress DOI Creative Commons
Xinglan Li, Yi Shan, Si Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 29, 2024

Glioma is a common and fatal malignant primary brain tumor. Radiotherapy first-line chemotherapy have little effect on the survival rate of patients, requiring alternative therapies. The main active ingredient Tripterygium wilfordii Hook. F. triptolide (TP) has been shown to anti-inflammatory anti-proliferative properties, along with wide range anticancer activities. This study aimed investigate molecular mechanisms in glioma treatment through network pharmacology experimental validation. Cell viability was first assessed using Counting Kit-8 (CCK8), followed by cell scratch assay migration ability. Apoptosis-related markers, including TUNEL staining, Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), were detected. Network used predict key targets glioma, detect its signal pathways, screen components for docking, explore signaling pathways TP. Lastly, immunofluorescence assays ELISA performed elucidate underlying mechanistic pathways. data suggested that TP may inhibit proliferation regulating pathway nuclear factor kappa-B (NF-κB). results showed mechanism involved regulation NF-κB promote generation reactive oxygen species, thereby enhancing oxidative stress response promoting apoptosis.

Language: Английский

Exploration and Identification of Potential Biomarkers and Immune Cell Infiltration Analysis in Synovial Tissue of Rheumatoid Arthritis DOI
Yi Zhao, Huifang Hu, Tao Chen

et al.

International Journal of Rheumatic Diseases, Journal Year: 2025, Volume and Issue: 28(2)

Published: Feb. 1, 2025

ABSTRACT Introduction Rheumatoid arthritis (RA) is a prevalent autoimmune disease with synovial inflammation and hyperplasia, which can potentially cause degradation of articular cartilage, ultimately causing joint deformity, impaired function. However, exact mechanisms underlying RA remain incompletely understood. This study seeks to uncover genomic signatures potential biomarkers RA, along exploring the biological processes involved. Methods Six microarray datasets from patients, osteoarthritis (OA) healthy controls (HC) tissue were obtained Gene Expression Omnibus (GEO) database for integrated analysis. Differentially expressed genes (DEGs) between groups identified by “limma” package. The gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses carried out. Protein–protein interaction (PPI) network was analyzed STRING presented Cytoscape. Weighted co‐expression analysis (WGCNA) conducted discover construct modules correlated clinical phenotype. CytoHubba MCODE utilized screening hub genes. Additionally, immune cell infiltration utilizing CIBERSORT algorithm. correlation cells examined through Pearson Correlation Analysis. Results overlapped 92 up‐regulated determined versus normal OA, primarily enriched in response, lymphocyte activation, chemokine signaling pathway. By integrating WGCNA, Cytohubba algorithms, 16 including CXCL13 , ITK CXCL9 CCR5 CCR7 NKG7 CD52 . We validated diagnostic significance these markers qRT‐PCR. Moreover, demonstrated positive association B naïve, plasma cell, T follicular helper, macrophages M1. abundance markedly greater compared OA controls. Conclusion research 5 tissue, namely GZMA These findings have enhanced our comprehension pathogenesis promising therapeutic targets RA.

Language: Английский

Citations

0
Exploring the mechanism of triptolide inhibiting the motility of fibroblast-like synoviocytes in rheumatoid arthritis via RhoA/Rho-associated kinase axis, based on network pharmacology, molecular docking and molecular dynamics simulations DOI Creative Commons
Jiacheng Shen,

Yuxuan Fang,

Nan Xu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the hyperproliferation and invasive behavior of rheumatoid fibroblast-like synoviocytes (RA-FLS), which contributes to degradation articular cartilage bone. Inhibition RA-FLS proliferation, migration invasion has become an important therapeutic strategy for RA. Triptolide (TPL), epoxy diterpene lactone compound from traditional Chinese medicine Tripterygium wilfordii Hook. f., significant immunosuppressive anti-inflammatory effects. However, specific mechanisms TPL-regulated effects on cytoskeleton inhibition metastasis are not yet fully explored. The aim this study was investigate skeleton reveal mechanism TPL-inhibition invasion. In vitro experiments were performed using cell line. Cell motility evaluated wound healing assay Transwell as well high content imaging system. Cytoskeletal remodeling observed cytoskeletal immunofluorescence staining transmission electron microscopy (TEM). Network pharmacology predicted targets Triptolide. RhoA/Rho-associated kinase signaling pathway detected quantitative real-time PCR Western blotting. Molecular docking molecular dynamics simulations used validate interaction with kinase. TPL significantly inhibited motility, reduced displacement cumulative distance RA-FLS. Cytoskeleton TEM observation showed after treatment. pharmacological prediction screened 45 associated intervention in RA via cytoskeleton, including TNF, KRAS, ESR1, RHOA, MAPK3 CASP3. pathway, treatment protein expression phosphorylation RhoA, Rock, Limk. can enter Rock1, Rock2 target binding domains stable activities, may cause conformational changes Rock1 related functions. inhibits regulating actin through action pathway.

Language: Английский

Citations

0
Therapeutic prospects and potential mechanisms of Prdx6: as a novel target in musculoskeletal disorders DOI Creative Commons
Hongbin Sun, Chao Xu,

Zhilin Xiong

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

With the global population aging, musculoskeletal disorders (MSDs) have posed significant physical and psychological health challenges for patients as well a substantial economic burden on society. The advancements in conservative surgical interventions MSDs been remarkable recent years; however, current treatment modalities still fall short of meeting optimal requirements patients. Recently, peroxiredoxin 6 (Prdx6) has gained considerable attention from researchers due to its antioxidative, anti-inflammatory, anti-apoptotic properties. It found that Prdx6 is involved multiple system diseases, including MSDs; exact role lacking. This study aimed summarize structure, regulatory mechanism, potential function Prdx6. These findings may demonstrate novel target inhibiting advancement MSDs.

Language: Английский

Citations

0
Triptolide alleviates psoriasis through inhibiting the Wnt5a/β-Catenin signaling pathway DOI Creative Commons

Eryang Chen,

Lei Wang,

Qu Wang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 29, 2025

Background Psoriasis, an immune-mediated chronic inflammatory skin disease, is characterized by keratinocyte proliferation and cell infiltration. T ripterygium wilfordii a potential treatment option for psoriasis, triptolide (TP) one of its active components. TP may possess the to treat psoriasis; however, mechanism action remains unknown. Objective The research aims explore therapeutic effect on psoriasis elucidate targets. Methods imiquimod-induced psoriasis-like lesion mouse model was used identify underlying TP.RNA-seq strategy utilized forecast targets mechanisms in context psoriasis.Finally, we verify IL-17A-induced hyperproliferation inflammation model. Results reduced epidermal hyperplasia as well area severity index scoring. Moreover, with inhibited IMQ-induced splenomegaly T-helper 17 differentiation psoriatic mice. Additionally, serum levels pro-inflammatory cytokines such interleukin (IL)-17A, IL-22, IL-23, IL-6, tumor necrosis factor-α sequencing RNA obtained from lesions mice indicated that significantly downregulated Wnt5a levels. Wnt5a/β-catenin pathway upregulated IMQ TP. IL-17A induced Wnt5A β-catenin mRNA expression, this expression HaCaT cells. Furthermore, proliferation, promoted apoptosis, arrested cycle model, thereby exhibiting anti-inflammatory properties. Conclusion alleviated exerting effects which partly achieved regulating signaling pathway.

Language: Английский

Citations

0
Triptolide induces apoptosis of glioma cells by inhibiting NF-κB activation during oxidative stress DOI Creative Commons
Xinglan Li, Yi Shan, Si Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 29, 2024

Glioma is a common and fatal malignant primary brain tumor. Radiotherapy first-line chemotherapy have little effect on the survival rate of patients, requiring alternative therapies. The main active ingredient Tripterygium wilfordii Hook. F. triptolide (TP) has been shown to anti-inflammatory anti-proliferative properties, along with wide range anticancer activities. This study aimed investigate molecular mechanisms in glioma treatment through network pharmacology experimental validation. Cell viability was first assessed using Counting Kit-8 (CCK8), followed by cell scratch assay migration ability. Apoptosis-related markers, including TUNEL staining, Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), were detected. Network used predict key targets glioma, detect its signal pathways, screen components for docking, explore signaling pathways TP. Lastly, immunofluorescence assays ELISA performed elucidate underlying mechanistic pathways. data suggested that TP may inhibit proliferation regulating pathway nuclear factor kappa-B (NF-κB). results showed mechanism involved regulation NF-κB promote generation reactive oxygen species, thereby enhancing oxidative stress response promoting apoptosis.

Language: Английский

Citations

0