Hydroxysafflor yellow A regulates lymphangiogenesis and inflammation via the inhibition of PI3K on regulating AKT/mTOR and NF-κB pathway in macrophages to reduce atherosclerosis in ApoE-/- mice

Feng, Xiaoteng; Du, Min; Li, Sijin; Zhang, Yifan; Ding, Jie; Wang, Jiarou; Wang, Yiru; Ping, Liu

doi:10.1016/j.phymed.2023.154684

Cited by 32 publications

(6 citation statements)

References 39 publications

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“…Additionally, our study further sheds light on the epigenetic mechanisms of arsenic-induced inhibition of FCGR2B and LYVE-1 expression that depend on H3K18ac regulation. At present, only the evidence from extrahepatic studies has elucidated the mechanisms of FCGR2B and LYVE-1 deficiency from the transcription factor pathways, such as the HIF-1α/PROX-1 and PI3K/AKT/mTOR pathways [55,56]. Our results provide new epigenetic evidence to understand the mechanism of LSEC dedifferentiation driven via the aberrant expression of cell surface receptors.…”

Section: Discussionmentioning

confidence: 75%

Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells

Hu,

Zhou,

Peng

et al. 2023

Toxics

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Arsenic pollution is a global environmental concern. Arsenic-induced chronic liver injury and its irreversible outcomes, including liver cirrhosis and liver cancer, threaten the health of residents in arsenic-contaminated areas. Liver fibrosis is a reversible pathological stage in the progression of arsenic-induced chronic liver injury to cirrhosis and liver cancer. The aim of this study is to identify the epigenetic mechanism of arsenic-induced liver fibrosis based on the dedifferentiation of liver sinusoidal endothelial cells (LSECs). Rats were treated with 0.0, 2.5, 5.0, or 10.0 mg/kg sodium arsenite for 36 weeks. Marked fibrotic phenotypes were observed in the rat livers, manifested by hepatic stellate cell activation and an increased extracellular matrix, as well as the deposition of collagen fibers. The reduced fenestrations on the cells’ surface and the increased expression of the dedifferentiation marker CD31 corroborated the LSECs’ dedifferentiation in the liver tissue, which was also found to be significantly associated with fibrotic phenotypes. We further revealed that arsenic exposure could inhibit the enrichment of histone H3 lysine 18 acetylation (H3K18ac) in the promoters of Fcgr2b and Lyve1, two key genes responsible for maintaining the differentiation phenotype of LSECs. This inhibition subsequently suppressed the genes’ expression, promoting LSEC dedifferentiation and subsequent liver fibrosis. In conclusion, arsenic can trigger liver fibrosis by inhibiting H3K18ac-dependent maintenance of LSEC differentiation. These findings uncover a novel mechanism of arsenic-induced liver fibrosis based on a new insight into epigenetically dependent LSEC dedifferentiation.

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Section: Discussionmentioning

confidence: 75%

Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells

Hu,

Zhou,

Peng

et al. 2023

Toxics

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“…This discovery indicates their potential through interaction to influence the pathogenesis of gout. Specifically, we examined a series of transcription factors, such as STAT3 and NF-κB, which play pivotal roles in regulating inflammation and immune responses and may be directly involved in the expression control of THBS3 and MTX1 [ 31 – 33 ]. These transcription factors might recognize and bind to specific sequences within the shared promoter region of THBS3 and MTX1, thereby modulating their expression.…”

Section: Discussionmentioning

confidence: 99%

Single-cell and genome-wide Mendelian randomization identifies causative genes for gout

Yang,

Hu,

Zhang

et al. 2024

Arthritis Res Ther

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Background Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. Methods The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. Results We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. Conclusion According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.

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“…[23] Additionally, it can exert significant antibacterial effects against a wide range of bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa , and Candida albicans . [24] Hydroxysafflor yellow A, an active ingredient in Carthamus tinctorius L ., can reduce inflammation by inhibiting PI3K and regulating AKT / mTOR and nuclear factor-κB ( NF-κB ) pathways in macrophages, [25] and can inhibit angiogenesis by inhibiting p38 MAPK phosphorylation, [26] although the specific mechanism of action remains unclear. Thus, in the present study, we explored the possible mechanisms of action of LXWHT in the treatment of the disease.…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Liang Xue Wu Hua Tang in the treatment of rosacea via network pharmacology and molecular docking

Cui,

Fan

2024

Medicine

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Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein–protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.

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Hydroxysafflor yellow A regulates lymphangiogenesis and inflammation via the inhibition of PI3K on regulating AKT/mTOR and NF-κB pathway in macrophages to reduce atherosclerosis in ApoE-/- mice

Cited by 32 publications

References 39 publications

Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells

Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells

Single-cell and genome-wide Mendelian randomization identifies causative genes for gout

Exploring the mechanism of Liang Xue Wu Hua Tang in the treatment of rosacea via network pharmacology and molecular docking

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