Exploration of chemical compositions in different germplasm wolfberry using UPLC-MS/MS and evaluation of the in vitro anti-inflammatory activity of quercetin DOI Creative Commons
Tian Lan, Guozhen Duan, Youchao Qi

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Wolfberry, esteemed as a traditional Chinese medicinal material and functional food, is replete with nutrients boasts diverse array of health benefits, including hypoglycemic, antitumor, antioxidant, anti-inflammatory, immune-enhancing properties. Notably, inflammation pivotal factor in the onset progression numerous diseases. Despite this, there paucity research on comprehensive evaluation components found different wolfberries, exploration their primary active limited. To address this issue, we conducted targeted metabolomics analysis, employing statistical methods such principal component analysis (PCA), orthogonal partial least squares discriminant (OPLS-DA), KEGG pathway volcano plots to delineate compositional differences among red, black, yellow wolfberries. Furthermore, investigated anti-inflammatory effects through vitro experiments. Our revealed total 1,104 chemical compositions three alkaloids, phenolic acids, flavonoids, lipids being predominant nutritional components. enrichment indicated that these were primarily involved biosynthesis secondary metabolites, ABC transport, galactose metabolism pathway. Moreover, our study demonstrated quercetin exhibited dose-dependent activity LPS-stimulated HUVECs. It effectively inhibited production inflammatory factors TNF-α, MCP-1, IL-1β, while also down-regulating gene protein expression levels ICAM-1 VCAM-1. In conclusion, findings indicate are variations flavonoids most abundant, studies confirmed potential quercetin. worth noting Lycium ruthenicum contains higher antioxidant possesses greater value, providing valuable insights for future development utilization

Language: Английский

Quercetin Attenuates KLF4-Mediated Phenotypic Switch of VSMCs to Macrophage-like Cells in Atherosclerosis: A Critical Role for the JAK2/STAT3 Pathway DOI Open Access
Lu Xiang, Yan Wang, Si Liu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7755 - 7755

Published: July 15, 2024

The objective of this study was to elucidate the protective role quercetin in atherosclerosis by examining its effect on phenotypic switch vascular smooth muscle cells (VSMCs) macrophage-like and underlying regulatory pathways. Aorta tissues from apolipoprotein E-deficient (ApoE KO) mice fed a high-fat diet (HFD), treated with or without 100 mg/kg/day quercetin, were analyzed for histopathological changes molecular mechanisms. Quercetin found decrease size atherosclerotic lesions mitigate lipid accumulation induced HFD. Fluorescence co-localization analysis revealed higher presence co-localizing phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer activator transcription 3 (p-STAT3), Krüppel-like factor 4 (KLF4) regions foam cell aggregation within aortic plaques. However, reduced following treatment quercetin. effectively inhibited KLF4-mediated oxidized low-density lipoprotein (ox-LDL)-loaded mouse (MOVAS), as indicated decreased expressions KLF4, LGALS3, CD68, F4/80, increased expression alpha actin (α-SMA), intracellular fluorescence Dil-ox-LDL uptake, accumulation. In contrast, APTO-253, KLF4 activator, reverse effects Furthermore, AG490, JAK2 inhibitor, counteracted ox-LDL-induced JAK2/STAT3 pathway-dependent phenotype MOVAS cells. These significantly mitigated but exacerbated coumermycin A1, activator. Our research illustrates that inhibits VSMCs reduces suppressing pathway.

Language: Английский

Citations

5
Berberine and its derivatives: mechanisms of action in myocardial vascular endothelial injury - a review DOI Creative Commons
Wenhui Zhang, Shengmin Guo,

Jinjin Dou

et al.

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

Published: March 4, 2025

Myocardial vascular endothelial injury serves as a crucial inducer of cardiovascular diseases. Mechanisms such endoplasmic reticulum stress, apoptosis, inflammation, oxidative autophagy, platelet dysfunction, and gut microbiota imbalance are intimately linked to this condition. Berberine its derivatives have demonstrated potential in modulating these mechanisms. This article reviews the pathogenesis myocardial vessels, pharmacological effects berberine derivatives, particularly their interactions with targets implicated injury. Furthermore, it discusses clinical applications, methods enhance bioavailability, toxicity concerns, aiming lay foundation for development BBR therapeutic agent

Language: Английский

Citations

0
The role of calprotectin in vascular calcification DOI

Ana Amaya-Garrido,

Julie Klein

Current Opinion in Nephrology & Hypertension, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Purpose of review Vascular calcification significantly contributes to cardiovascular morbidity and mortality, particularly in high-risk populations like chronic kidney disease (CKD) patients. Calprotectin, a heterodimeric protein with pro-inflammatory pro-calcific properties, has emerged as key molecule vascular pathology. This highlights the mechanisms linking calprotectin calcification, its clinical relevance, potential therapeutic target. Recent findings is an active, cell-mediated process involving smooth muscle cell (VSMC) dysfunction, inflammation, matrix remodeling, cellular senescence. Calprotectin strongly associated CKD. Mechanistic studies reveal that promotes through activation RAGE TLR4 signaling pathways, driving inflammatory cascades. Preclinical demonstrate pharmacological inhibition attenuates animal models, supporting Summary emerging promising biomarker target CKD aging-related diseases. However, further are required clarify assess long-term efficacy safety calprotectin-targeted therapies. A deeper understanding calprotectin's multifaceted role could pave way for innovative strategies targeting both inflammation mineralization calcification-related

Language: Английский

Citations

0
Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition DOI Creative Commons
Mehdi Razazian,

Sheyda Bahiraii,

Azmat Sohail

et al.

Aging, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Medial vascular calcification is highly prevalent in advanced age and chronic kidney disease (CKD), where it associated with increased risk for cardiovascular events mortality. Vascular smooth muscle cells (VSMCs) actively regulate this process, which can be augmented by inflammation cellular senescence. Thus, the present study investigated impact of fisetin, a flavonol anti-inflammatory senolytic properties, on VSMC calcification. Fisetin treatment suppressed calcific marker expression VSMCs as well p38 MAPK phosphorylation induced pro-calcific conditions. These effects were abolished silencing dual-specificity phosphatase 1 (DUSP1), negative regulator activity. Moreover, knockdown DUSP1 alone was sufficient to increase VSMCs, blunted pharmacological inhibition. Accordingly, aggravated during In addition, fisetin ameliorated uremic conditions exposed serum from dialysis patients. also inhibited ex vivo mouse aortic explants high phosphate cholecalciferol overload model. conclusion, acts potent anti-calcific agent calcification, an effect involving DUSP1-mediated regulation MAPK-dependent signaling.

Language: Английский

Citations

0
METTL3-mediated N6-methyladenosine modification contributes to vascular calcification DOI Creative Commons
Long Li, Qing Chai,

Chunling Guo

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Vascular calcification (VC) is a major adverse cardiovascular event in chronic kidney disease (CKD) patients. N6-methyladenosine (m6A) modification vital for many biological processes, but its function and possible molecular mechanisms VC are poorly understood. This study aimed to clarify the of N6-adenosine-methyltransferase-like 3 (METTL3) VC. The results bioinformatic analysis showed that METTL3 expression was significantly upregulated calcified VSMCs. finding corroborated by phosphate-induced VSMCs models 5/6 nephrectomy-induced CKD mouse models. Afterward, Alizarin Red S staining m6A dot blot demonstrated overexpression elevated levels encouraged aortic rings, while knockdown decreased inhibited calcium deposition these experimental Furthermore, promoted via PTEN/AKT pathway, MeRIP verified induced PTEN mRNA degradation modifying it with m6A. In addition, docking simulations DARTS assays revealed quercetin natural small-molecule inhibitor METTL3. current investigation mitigated reducing METTL3-dependent vivo vitro. conclusion, this unraveled pathogenic mechanism METTL3-mediated provided new insights establish as therapeutic target

Language: Английский

Citations

0
A Dynamic Cellular Model as an Emerging Platform to Reproduce the Complexity of Human Vascular Calcification In Vitro DOI Open Access
Elisa Ceccherini, Elisa Persiani, Manuela Cabiati

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7427 - 7427

Published: July 6, 2024

Vascular calcification (VC) is a cardiovascular disease characterized by calcium salt deposition in vascular smooth muscle cells (VSMCs). Standard vitro models used VC investigations are based on VSMC monocultures under static conditions. Although these platforms easy to use, the absence of interactions between different cell types and dynamic conditions makes insufficient study key aspects pathophysiology. The present aimed develop endothelial cell-VSMC co-culture that better mimics vivo microenvironment. A double-flow bioreactor supported cellular reproduced blood flow dynamic. was stimulated with DMEM high glucose medium supplemented 1.9 mM NaH2PO4/Na2HPO4 (1:1) for 7 days. Calcification, viability, inflammatory mediators, molecular markers (SIRT-1, TGFβ1) related differentiation were evaluated. Our model able reproduce inflammation evidenced differences modulation effectors involved calcified phenotype compared standard monocultures, highlighting importance microenvironment controlling behavior. Hence, our platform represents an advanced system investigate pathophysiologic mechanisms underlying VC, providing information not available monoculture.

Language: Английский

Citations

2
Dietary inflammation and vascular calcification: a comprehensive review of the associations, underlying mechanisms, and prevention strategies DOI
Xinhai Cui, Wendi Wei, Yuanlong Hu

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 22

Published: Sept. 27, 2024

Cardiovascular disease (CVD) is one of the leading causes death globally, and vascular calcification (VC) has been recognized as an independent strong predictor global CVD mortality. Chronic inflammation demonstrated to play a significant role in progression VC. This review aims summarize literature that aimed elucidate associations between dietary (DI) VC well explore mechanisms underlying association discuss strategies (including interventions) prevent Notably, diets rich processed foods, carbohydrates with high glycemic index/load, saturated fatty acids,

Language: Английский

Citations

1
Exploration of chemical compositions in different germplasm wolfberry using UPLC-MS/MS and evaluation of the in vitro anti-inflammatory activity of quercetin DOI Creative Commons
Tian Lan, Guozhen Duan, Youchao Qi

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Wolfberry, esteemed as a traditional Chinese medicinal material and functional food, is replete with nutrients boasts diverse array of health benefits, including hypoglycemic, antitumor, antioxidant, anti-inflammatory, immune-enhancing properties. Notably, inflammation pivotal factor in the onset progression numerous diseases. Despite this, there paucity research on comprehensive evaluation components found different wolfberries, exploration their primary active limited. To address this issue, we conducted targeted metabolomics analysis, employing statistical methods such principal component analysis (PCA), orthogonal partial least squares discriminant (OPLS-DA), KEGG pathway volcano plots to delineate compositional differences among red, black, yellow wolfberries. Furthermore, investigated anti-inflammatory effects through vitro experiments. Our revealed total 1,104 chemical compositions three alkaloids, phenolic acids, flavonoids, lipids being predominant nutritional components. enrichment indicated that these were primarily involved biosynthesis secondary metabolites, ABC transport, galactose metabolism pathway. Moreover, our study demonstrated quercetin exhibited dose-dependent activity LPS-stimulated HUVECs. It effectively inhibited production inflammatory factors TNF-α, MCP-1, IL-1β, while also down-regulating gene protein expression levels ICAM-1 VCAM-1. In conclusion, findings indicate are variations flavonoids most abundant, studies confirmed potential quercetin. worth noting Lycium ruthenicum contains higher antioxidant possesses greater value, providing valuable insights for future development utilization

Language: Английский

Citations

0