2-Dodecyl-6-methoxycyclohexa-2,5-dien-1,4-dione alleviates liver fibrosis and improves intestinal flora and bile acid metabolism DOI Creative Commons
Yongfei He, Thi Thai Hoa Pham, Junming Xu

et al.

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

Published: May 16, 2025

Background The bioactive compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD), derived from the horn root of star fruit, exhibits therapeutic promise through its modulation TGF-β1 pathway and regulation bile acids. Methods In this study, a liver fibrosis model was established in Kunming mice (KM) induced by carbon tetrachloride (CCL4), DMDD (50 mg/kg) administered intragastrically. HE staining, Masson Sirius staining were used to evaluate effect on fibrosis. Illumina sequencing platform detect intestinal flora transcriptome information mouse feces, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology acid content changes feces. Results results show that can mitigate fibrosis-induced damage mice, potentially suppression TGF-β/Smad signaling pathway. Furthermore, increased abundance Lactobacillus , Bacteroides Ruminococcaceae Ruminococcus Oscillospira thereby addressing disturbances regulating metabolism. Conclusion Our study suggests alleviates inhibiting pathway, restoring gut microbiota homeostasis, balancing

Language: Английский

CAV1 promotes epithelial-to-mesenchymal transition (EMT) and chronic renal allograft interstitial fibrosis by activating the ferroptosis pathway DOI Creative Commons

Qianguang Han,

Bing Ni,

Wei Bao

et al.

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

Published: Feb. 12, 2025

Background Chronic allograft dysfunction (CAD) stands as a critical factor that limits the long-term viability of transplanted kidneys. Ferroptosis is an iron-dependent form programmed cell death increasingly linked to chronic fibrosis. However, mechanism by which ferroptosis contributes onset and progression CAD remains unclear. Methods This study analyzed transcriptome data from renal transplant biopsy samples in Gene Expression Omnibus (GEO), through clinical samples, animal models, experiments, this investigated Caveolin-1 (CAV1) promotes regulation pathway. Results The elevated levels CAV1 were found positively correlate with incidence. Clinical model validation confirmed heightened expression CAD. In vitro experiments demonstrated can directly promote interstitial fibrosis regulating tubular epithelial cells; additionally, it epithelial-to-mesenchymal transition (EMT) secreting Interleukin- 6 (IL-6), thereby further contributing Conclusion plays role development promoting EMT Adjusting altering abundance may become important method for prevention treatment future.

Language: Английский

Citations

0
Mesenchymal stem cell-derived extracellular vesicles attenuate ferroptosis in aged hepatic ischemia/reperfusion injury by transferring miR-1275 DOI Creative Commons
Yihang Gong,

Qiang You,

Xiaofeng Yuan

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103556 - 103556

Published: Feb. 18, 2025

Language: Английский

Citations

0
THBS1 in macrophage-derived exosomes exacerbates cerebral ischemia–reperfusion injury by inducing ferroptosis in endothelial cells DOI Creative Commons
Chang Liu, Haijing Sui, Zhixi Li

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 24, 2025

Macrophages play a critical role in the development of acute ischemic stroke (AIS). Cerebral ischemia–reperfusion injury (CIRI) is pivotal pathological process that exacerbates AIS, with exosomes act as crucial mediators. However, effects and mechanisms action macrophage-derived on CIRI remain unclear. This study demonstrated induce endothelial ferroptosis barrier disruption during CIRI. Through proteomic sequencing reanalysis transcriptomic single-cell data, thrombospondin-1 (THBS1) was identified key exosomal molecule. Elevated THBS1 observed monocytes from peripheral blood patients AIS oxygen–glucose deprivation/reoxygenation (OGD/R)-stimulated THP-1 RAW264.7, their secreted exosomes, macrophages within brains transient middle cerebral artery occlusion (tMCAO) mice. Additionally, expression positively correlated vascular biomarkers, including MMP-9 S100B. Modulation affected exosome-induced cells. The mechanism by which binds directly to OTUD5 promotes GPX4 ubiquitination elucidated using RNA interference, adeno-associated virus transfection, endothelial-specific Gpx4 knockout High-throughput screening small-molecule compounds targeting performed. Molecular docking, molecular dynamics simulations, cellular thermal shift assays further confirmed salvianolic acid B (SAB) has potent binding affinity for THBS1. SAB treatment inhibited interaction between OTUD5, leading reduced ubiquitination. Further research revealed enhanced protective inhibition. In conclusion, this explored exosome-mediated signaling cells CIRI, highlighting THBS1-OTUD5-GPX4 axis driver brain injury. Targeting represents potential therapeutic strategy treating

Language: Английский

Citations

0
Ferroptosis in organ fibrosis: Mechanisms and therapeutic approaches DOI

Zhi-Hong Ning,

Xiuheng Wang, Yue Zhao

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114341 - 114341

Published: March 1, 2025

Language: Английский

Citations

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Salvianolic acid B ameliorates hepatic fibrosis via inhibiting p300/CBP DOI
Lili Li, Hang Zhou, Miaomiao Li

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177495 - 177495

Published: March 1, 2025

Language: Английский

Citations

0
Chinese Medicine for the Treatment of Liver Cirrhosis: The Mechanism of Cellular Autophagy DOI
Shihao Zheng,

Tianyu Xue,

Qiuyue Wang

et al.

The American Journal of Chinese Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: March 12, 2025

Liver cirrhosis is a critical stage in the progression of various chronic liver diseases, often leading to severe complications such as ascites, hepatic encephalopathy, and high mortality rate, it thus poses serious threat patient life. The activation stellate cells central driver disease progression. Cellular autophagy, lysosome-mediated degradation process, plays key role maintaining cellular function dynamic homeostasis. Research has shown that autophagy closely associated with proteins like LC3, Beclin-1, P62, mTOR, regulated through signaling pathways PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, AMPK/mTOR. Additionally, relationship between apoptosis, well exosomes, been further demonstrated. While modern medicine made progress treating cirrhosis, still faces significant limitations. By contrast, numerous studies have demonstrated efficacy traditional Chinese preventing by regulating fewer adverse effects. herbal monomers formulations can modulate autophagy-related pathways, including AMPK/mTOR, influence LC3 Beclin-1. This modulation inhibits cell activation, reduces extracellular matrix deposition, exerts anticirrhotic Moreover, appears reduce reactions treatment lower risk recurrence. review explores mechanisms prevention medicine, offering new insights for development medicinal therapies their rational clinical application.

Language: Английский

Citations

0
Tiaojing Cuyun Recipe inhibits ferroptosis through SLC7A11/GSH/GPX4 axis to improve endometrial receptivity of mice with embryo implantation dysfunction DOI Creative Commons

Hui Xue,

Siqing Huang,

Yanqiu Xia

et al.

Journal of Traditional and Complementary Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
SMND-309 activates Nrf2 signaling to alleviate acetaminophen-induced hepatotoxicity and oxidative stress DOI Creative Commons
Yao Dong, Ru Jia, Yujie Jiang

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0310879 - e0310879

Published: March 31, 2025

Background Acetaminophen (APAP) can be used for pain relief and fever alleviation, the overdose of which, however, may lead to accumulation N-acetyl-p-benzoquinone imine (NAPQI), inducing oxidative stress liver damage. The natural compound SMND-309 has been shown have hepatoprotective effects potential antioxidant activity. However, its ability alleviate acetaminophen-induced acute injury (AILI) not elucidated. Objective To explore protective effect against AILI mechanism. Methods model was established using a mouse HepG2 cells pathological evaluation biochemical assays tissues assess level injury. on cellular ROS levels mitochondrial membrane were detected DCFH-DA JC-1 probes. Western blotting performed detect expressions Nrf2 signaling pathway key proteins related APAP metabolism in combination immunohistochemistry tissues, with immunofluorescence assay whether undergoes nuclear translocation. Molecular docking, molecular dynamics simulation (MD) biofilm layer interference (BLI) experiments interaction Keap1. Results improved histopathological changes liver, decreased alanine aminotransferase (ALT), aspartate (AST), lactate dehydrogenase (LDH) levels, as well attenuated dysfunction cell line. Further studies revealed that promoted translocation upregulated glutamate-cysteine ligase catalytic subunit (GCLC), heme oxygenase 1 (HO-1) NAD(P)H quinone (NQO1). In addition, docking MD suggested could bind Keap1 identified possible binding modes, BLI confirming directly interacted Conclusion exerts an Nrf2-ARE pathway-dependent manner.

Language: Английский

Citations

0
Quantitative analysis of drug–drug interactions among active components of Xuebijing in inhibiting LPS-induced TLR4 signaling and NO production DOI Creative Commons
Tianshu Zhang, Hongyuan Li, Cong Lin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 1, 2025

Despite the long history of Traditional Chinese Medicine (TCM) in disease treatment, underlying "Jun–Chen–Zuo–Shi" principle remains largely unexplored. To address this gap, it is essential to elucidate interactions between active substances TCM through quantitative molecular and cellular pharmacology. The Chou–Talalay method particularly effective for investigating drug combinations, making highly relevant formulas. This study employed explore drug–drug Xuebijing (XBJ), a formula used treating sepsis. aim was by main XBJ: danshensu salvianolic acid B (from Radix Salviae Miltiorrhizae), senkyunolide A Rhizoma Chuanxiong), ligustilide Angelicae Sinensis), safflower yellow hydroxysafflor Flos Carthami), paeoniflorin Paeoniae Rubra). We quantitatively analyzed their TLR4 antagonistic activities combination index (CI) quantify interactions, revealing synergism (CI < 1), additive effects = antagonism > 1). results show these agents inhibit nitric oxide (NO) production, with some combinations demonstrating synergistic at certain concentrations, while others present effects. Understanding provides scientific foundation optimizing formulations, enhancing quality control, efficacy, safety.

Language: Английский

Citations

0
MST1/2 DKO abates salvianolic acid B’s therapeutic effect on CCl4-induced liver injury mice DOI
Yanyan Xu, Yu Zhang, Mengru Yang

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Language: Английский

Citations

0