Oleracein E Rejuvenates Senescent Hippocampal NSCs by Inhibiting the ERK1/2‐mTOR Axis to Improve Cognitive Dysfunction in Vascular Dementia DOI
Haili Lang, Jie Zeng, Yuqi Wen

et al.

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(9)

Published: May 1, 2025

ABSTRACT Vascular dementia (VD) is one of the most prevalent forms dementia, yet effective treatments remain limited. Our previous research identified hippocampal neural stem cells (hNSCs) senescence as a key contributor to VD progression and suggested that reducing hNSC could help reverse cognitive impairment. In this study, we investigated whether Oleracein E (OE), phenolic antioxidant alkaloid, alleviate improve function in VD. Using two‐vessel occlusion mouse model VD, found OE treatment significantly reduced hNSCs senescence, restored proliferation neuronal differentiation capacities, improved performance. Mechanistically, exerted its effects by inhibiting ERK1/2 phosphorylation suppressing mTOR activation. Furthermore, pharmacological activation with MHY1485 partially abolished antisenescence hNSCs. These findings suggest may counteract senescence‐related neurogenesis dysfunction decline highlighting potential therapeutic intervention.

Language: Английский

cGAS-STING targeting offers novel therapeutic opportunities in neurological diseases DOI
Hongquan Wang, Joshua S. Fleishman, Shuang Wu

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 105, P. 102691 - 102691

Published: Feb. 13, 2025

Language: Английский

Citations

2
Bioinformatics-Based Exploration of the Ability of Ginkgetin to Alleviate the Senescence of Cardiomyocytes After Myocardial Infarction and Its Cardioprotective Effects DOI Creative Commons
Han Li,

Dongsheng Wei,

Huimin Cao

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 301 - 323

Published: Jan. 1, 2025

Myocardial infarction (MI) is a prevalent cardiovascular disorder affecting individuals worldwide. There need to identify more effective therapeutic agents minimize cardiomyocyte damage and enhance cardioprotection. Bioinformatics analysis was performed predict the underlying biological mechanisms of ginkgetin in treatment MI. Next, we further validation through experiments. For vivo studies, used coronary ligation construct an MI rat model. In vitro, oxygen glucose deprivation (OGD) simulate ischemia H9c2 cardiomyocytes. revealed that key targets for were MMP2, MMP9, VEGFA. Immune infiltration might be involved immune regulation by acting on TCR signaling pathway. The results GO enrichment protect heart cell membrane alleviate senescent apoptosis cardiomyocytes after studies ameliorated myocardial pathological cardiac decompensation It also alleviated inflammatory Additionally, can downregulate activation signals pathway dephosphorylating CD3 CD28. vitro attenuated elevated OGD-induced cytotoxicity, increased viability, apoptosis, thus protecting Ginkgetin inhibits postinfarction fibrosis hypertrophy, scavenges free radicals, decreases limbic infiltration, suppresses inflammatory-immune pathway, delays peripheral cells from undergoing heart.

Language: Английский

Citations

1
Liver‐Secreted Extracellular Vesicles Promote Cirrhosis‐Associated Skeletal Muscle Injury Through mtDNA‐cGAS/STING Axis DOI Creative Commons
Xiaoli Fan, Yunke Peng, Bo Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic inflammation plays pivotal role in its pathologenesis. However, the detailed mechanism through which injured tissues mediate skeletal inflammatory injury remains elusive. Here, it reported that hepatocytes might secrete mtDNA‐enriched extracellular vesicles (EVs) to trigger by activating cGAS‐STING pathway. Briefly, secreted increased amounts EVs into circulation, are then engulfed primarily macrophages subsequently induce signaling its‐mediated response muscles. In contrast, suppression hepatic EV secretion or STING significantly alleviated cirrhosis‐induced vivo. Circulating from cirrhotic patients showed higher levels mtDNA, EV‐mtDNA positively correlated with severity injury. hepatocytes, mitochondrial damage promoted release cytosolic mtDNA subsequent EVs. This study reveals hepatocyte‐derived via mtDNA‒STING axis, while targeted blockade represents potential therapeutic approach for preventing cirrhosis‐associated atrophy.

Language: Английский

Citations

1
STING Inhibitors and Degraders: Potential Therapeutic Agents in Inflammatory Diseases DOI

Kerong Wu,

Yiwen Xu,

Peizhao Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117632 - 117632

Published: April 15, 2025

Language: Английский

Citations

0
Petroselinic Acid from Apiaceae Family Plants Ameliorates Autoimmune Disorders Through Suppressing Cytosolic-Nucleic-Acid-Mediated Type I Interferon Signaling DOI Creative Commons

Yue Guo,

Yunying Wang, Yao Wang

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 329 - 329

Published: Feb. 24, 2025

The recognition of cytosolic nucleic acids is a critical step in the host immune response against danger signals, such as molecular patterns from pathogens or tissue damage. Nonetheless, over-reactivity to self-nucleic leads sustained production type I interferon (IFN), mediated either by cGAS RLR, contributing pathogenesis certain autoimmune diseases, Aicardi–Goutières syndrome (AGS). Therefore, inhibiting excessive IFN represents potential therapeutic strategy for conditions. In this study, we discovered that petroselinic acid (PA), natural compound isolated Apiaceae family plants, effectively suppresses induced acids. Mechanistic investigations revealed PA inhibits phosphorylation TBK1 and IRF3, which are key nodal proteins within pathway. Notably, docking suggests binding between sensors, RIG-I. Moreover, found attenuates expression their downstream interferon-stimulated genes (ISGs) models AGS disease characterized accumulation. Thus, our research identifies offers promising treating diseases resulting aberrant hyperactivation interferon.

Language: Английский

Citations

0
Natural products in traditional Chinese medicine for renal fibrosis: a comprehensive review DOI Creative Commons
Qianqian Zhao, Meihua Jin, Qiang Zhao

et al.

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

Published: April 16, 2025

Renal fibrosis represents the terminal pathological manifestation of most chronic kidney diseases, driving progressive loss renal function. Natural products have emerged as promising therapeutic agents for preventing and ameliorating due to their multi-target efficacy favorable safety profiles. In this review, we conducted a comprehensive literature search on PubMed using keywords "natural product" "renal fibrosis" from 2004 2025, identifying 704 relevant articles. We systematically categorize discuss biological effects key natural formulations with antifibrotic potential, focusing five major classes: glycosides, flavonoids, phenolic compounds, anthraquinones, terpenoids. Representative compounds each category are highlighted mechanisms action, including modulation oxidative stress, inflammation, autophagy, signaling pathways. This review aims provide theoretical foundation development product-based therapies combat fibrosis, offering insights into potential future research directions.

Language: Английский

Citations

0
Therapeutic targeting the cGAS−STING pathway associated with protein and gene: An emerging and promising novel strategy for aging-related neurodegenerative disease DOI

Qiongli Zhou,

Jiekun Luo, X. Chai

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114679 - 114679

Published: April 18, 2025

Language: Английский

Citations

0
Discovery of 3-(Fluoro-imidazolyl)pyridazine Derivatives as Potent STING Agonists with Antitumor Activity DOI
Hui Hou, Jingyi Zhou, Qibang Sui

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Stimulator of interferon genes (STING) represents a promising therapeutic target for cancer and infectious diseases due to its ability activate innate immune responses. Herein, we describe the discovery 3-(fluoro-imidazolyl) pyridazine derivatives as potent STING agonists. Our comprehensive investigation, including structural functional analysis well molecular dynamics simulation, suggests that appropriate spatial dimensions may play crucial role in determining agonist efficacy. Notably, our representative A4 demonstrates remarkable binding affinities various hSTING variants mSTING, effectively activating both human THP1 mouse RAW 264.7 cells with EC50 values 0.06 14.15 μM, respectively. Furthermore, Compound exhibits an excellent pharmacokinetic profile C57BL/6 mice, systemic administration led significant tumor regression B16.F10 tumor-bearing surpassing efficacy SR-717. These findings position highly warranting further advanced preclinical development immunotherapy.

Language: Английский

Citations

0
Oleracein E Rejuvenates Senescent Hippocampal NSCs by Inhibiting the ERK1/2‐mTOR Axis to Improve Cognitive Dysfunction in Vascular Dementia DOI
Haili Lang, Jie Zeng, Yuqi Wen

et al.

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(9)

Published: May 1, 2025

ABSTRACT Vascular dementia (VD) is one of the most prevalent forms dementia, yet effective treatments remain limited. Our previous research identified hippocampal neural stem cells (hNSCs) senescence as a key contributor to VD progression and suggested that reducing hNSC could help reverse cognitive impairment. In this study, we investigated whether Oleracein E (OE), phenolic antioxidant alkaloid, alleviate improve function in VD. Using two‐vessel occlusion mouse model VD, found OE treatment significantly reduced hNSCs senescence, restored proliferation neuronal differentiation capacities, improved performance. Mechanistically, exerted its effects by inhibiting ERK1/2 phosphorylation suppressing mTOR activation. Furthermore, pharmacological activation with MHY1485 partially abolished antisenescence hNSCs. These findings suggest may counteract senescence‐related neurogenesis dysfunction decline highlighting potential therapeutic intervention.

Language: Английский

Citations

0