Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis DOI

Huicai Lin,

Zhongyuan Wen,

Linying Feng

et al.

International Journal of Drug Discovery and Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 100025 - 100025

Published: Dec. 17, 2024

Article Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis Huicai Lin 1,2,3, Zhaoqin Wen Linying Feng Xiaoyan Chen 4, Yongxiang Song 5, Jiang Deng 1,2,3,* 1 Key Laboratory of Basic Pharmacology Ministry Education Joint International Research Ethnomedicine Education, Zunyi Medical University, Zunyi563006, China 2 Guizhou Province, 3 The Second Affiliated Hospital 4 Department Pathophysiology, 5 Thoracic Surgery, * Correspondence: [email protected]; Tel.: +86-851-2864-3411; Fax: +86-851-2864-3411 Received: 30 August 2024; Revised: 28 September Accepted: Published: 17 December 2024 Abstract: fibrosis (PF) is a chronic, progressive, irreversible, fibrotic interstitial lung disease with high mortality. (G-Re) one active components ginseng, which has been proven to possess multiple pharmacological effects, including anti-inflammatory antioxidant. Thus, G-Re considered potential therapeutic agent for treating PF. present study explored protective mechanisms against bleomycin (BLM)-induced PF mice its as strategy A mouse model BLM-induced was utilized assess effect treatment, N-acetylcysteine (NAC) set positive control agent. Various parameters such function, histopathological changes, oxidative stress markers, nuclear factor erythroid 2-related (Nrf2) translocation related protein expressions, Kelch-like ECH-associated (Keap1), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase (NQO-1), ferroptosis signature glutathione peroxidase (GPX4) were evaluated. Continuous administration 14 days significantly reduced injury, enhanced antioxidant capacity, activated Nrf2/Keap1 signaling pathway, inhibited evidenced GPX4. Additionally, treatment collagen deposition, improved pulmonary alleviated tissue mice. These findings demonstrate that exerts effects modulating targeting pathways, highlighting intervention providing insights into molecular underlying effects.

Language: Английский

Trilobatin suppresses aging-induced cognitive impairment by targeting SIRT2: Involvement of remodeling gut microbiota to mediate the brain-gut axis DOI
Dianyou Xie, Lin Mu,

Yun-mei Luo

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155744 - 155744

Published: May 15, 2024

Language: Английский

Citations

6
Astrocyte modulation in cerebral ischemia-reperfusion injury: A promising therapeutic strategy DOI
Ziyu Wang, Xiaolu Zhang, Guangming Zhang

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 378, P. 114814 - 114814

Published: May 16, 2024

Language: Английский

Citations

4
Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia‐Reperfusion DOI Creative Commons
Yu yong Jiang,

Hua He,

Xinwei Jia

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 26, 2025

Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as kidneys liver. This study explores protective effects of oxycodone on myocardial I/R its underlying mechanisms. Using model in Sprague-Dawley (SD) rats an oxygen-glucose deprivation/reoxygenation (OGD/R) H9c2 cells, we administered inhibited AMP-activated protein kinase (AMPK) with Compound C (C.C). Our results showed that significantly reduced lactate dehydrogenase (LDH) release reactive oxygen species (ROS) production while stabilizing mitochondrial membrane potential (MMP). Western blot RT-qPCR analyzes confirmed enhances AMPK phosphorylation upregulates expression Silent Information Regulator 1 (SIRT1) Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α), thereby protecting cells. These findings suggest exerts against by activating pathway, offering new therapeutic targets for protection.

Language: Английский

Citations

0
Targeting FDX1 by trilobatin to inhibit cuproptosis in doxorubicin‐induced cardiotoxicity DOI Open Access
Jiajia Wei,

Gongchun Lan,

Wenfang Zhang

et al.

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract Background and Purpose Doxorubicin (DOX), an anthracycline chemotherapeutic agent, whose use is limited owing to its dose‐dependent cardiotoxicity. Mitochondrial oxidative stress plays a crucial role in the pathogenesis of DOX‐induced cardiotoxicity (DIC). Trilobatin (TLB), naturally occurring food additive, exhibits strong antioxidant properties, but cardioprotective effects DIC unclear. This study investigates effect TLB on DIC. Experimental Approach DOX was used generate vivo vitro model Echocardiography, enzyme‐linked immunosorbent assay (ELISA) haematoxylin eosin (H&E) staining were evaluate cardiac function these models. To identify targets TLB, RNA‐sequence analysis, molecular dynamics simulations, surface plasmon resonance binding assays protein immunoblotting techniques used. Transmission electron microscopy, along with dihydroethidium Mito‐SOX staining, conducted examine impact trilobatin mitochondrial stress. SiRNA transfection performed confirm ferredoxin 1 (FDX1) development. Key Results In mice, improved manner inhibited myocardial fibrosis mice. also attenuated dysfunction reduced found directly bind FDX1 suppresses cuproptosis after treatment, causing significant inhibition cuproptosis‐related proteins. Conclusions Implications first show that strongly inhibits by reducing controlling DOX‐mediated targeting FDX1. Therefore, as potential phytochemical candidate for ameliorating

Language: Английский

Citations

0
Trilobatin, a Naturally Occurring GPR158 Ligand, Alleviates Depressive-like Behavior by Promoting Mitophagy DOI Creative Commons
Lin Mu, Dianyou Xie,

Yunmei Luo

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: 73(9), P. 5163 - 5179

Published: Feb. 18, 2025

The G-protein-coupled receptor (GPR158), an orphan receptor, is highly expressed in the medial prefrontal cortex (mPFC) and identified as a novel therapeutic target for depression. Trilobatin naturally occurring food additive with potent neuroprotective properties. However, its pharmacological effects molecular mechanisms against depression remain unknown. Therefore, we explored whether trilobatin alleviates by targeting GPR158. Our results indicated that alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behavior mice. Mitophagy contributed to antidepressant-like effect of trilobatin, evidenced qRT-PCR array. Furthermore, up-regulated autophagy-associated protein expression, restored mitochondrial dynamic balance, inhibited oxidative mPFC mice after CUMS insult corticosterone-induced primary neuron injury. Intriguingly, directly bound GPR158 decreased level expression. deficiency attenuated through promoting mitophagy, while antidepressant was strengthened GPR158-deficient findings highlight GPR158-mediated mitophagy acts crucial reveal new-found property trilobatin: serving ligand safeguard from mitophagy.

Language: Английский

Citations

0
Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4 DOI Creative Commons
Jun Tang,

Jianhe Yue,

Yihao Tao

et al.

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Perihematomal edema (PHE) significantly aggravates secondary brain injury in patients with intracerebral hemorrhage (ICH), yet its detailed mechanisms remain elusive. Neutrophil extracellular traps (NETs) are known to exacerbate neurological deficits and worsen outcomes after stroke. This study explores the potential role of NETs pathogenesis following ICH. The rat ICH model was created, immunofluorescence Western blot were used examine neutrophil accumulation, NET markers citrullinated histone H3 (CitH3) myeloperoxidase (MPO), tight junction proteins (ZO-1 Occludin), Aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), ERK phosphorylation (p-ERK) tissues surrounding hematoma. TUNEL staining behavioral tests employed evaluate neuronal apoptosis dysfunction, while blood-brain barrier (BBB) permeability also measured by Evans blue water content. Furthermore, molecular related NETs-induced PHE investigated using NETs, ERK, MMP-9 AQP4 regulators, respectively. Ly6G+ neutrophils hematoma developed within 3 days post-ICH. decreased proteins, destroyed BBB integrity, promoted edema, increased apoptosis, exacerbated deficits. Conversely, inhibition mitigated PHE, reduced improved functions. Mechanistically, NET-induced originated from impairment via ERK/MMP9 pathway, coupled ERK-mediated downregulation perihematomal regions. These findings elucidated effects on which offered promising insights for targeting relieve

Language: Английский

Citations

2
Discovery of specific inhibitors of Porphyromonas gingivalis gingipains from food-derived flavonoids by high-throughput virtual screening and molecular simulations DOI
Desheng Wu, Xiaohan Liu, Xiaofeng Li

et al.

Food Bioscience, Journal Year: 2024, Volume and Issue: 61, P. 104596 - 104596

Published: June 19, 2024

Language: Английский

Citations

2
Lithocarpus polystachyus Rehd. leaves aqueous extract inhibits learning and memory impairment in Alzheimer's disease rats: Involvement of the SIRT6/NLRP3 signaling pathway DOI Creative Commons
Wendan Wu,

You Yan,

Tingting Yi

et al.

Ibrain, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Alzheimer's disease (AD) is a chronic and progressive neurodegenerative condition that influenced by multiple factors along with neuroinflammation oxidative stress. Our previous study proved Lithocarpus polystachyus Rehd. aqueous extract (sweet tea extract, STAE) effectively inhibits hydrogen peroxide‐induced neuronal cell injury. However, it not clear whether STAE can protect against AD, its underlying mechanisms are still uncertain. Therefore, the present was designed to evaluate possible behavioral neurochemical effects of on A β 25‐35 ‐induced AD rats administered (20, 40, 80 mg/mL) for 14 days. We showed administration significantly dose‐dependently ameliorated cognitive deficits in rat models, assessed Morris water maze (MWM) test, Y‐maze novel object recognition (NOR) test. The results hematoxylin eosin (H&E) staining Nissl after treatment STAE, pathological damage hippocampal CA1, CA3, dentate gyrus (DG) neurons improved. Furthermore, inhibited microglia astrocyte activation hippocampus accompanied increased protein expression silent mating‐type information regulation 2 homolog 6 (SIRT6) decreased nod‐like receptor thermal domain‐associated 3 (NLRP3) downstream pyroptosis‐related genes following . In summary, our findings indicate learning memory impairment rats, mechanism is, at least partially, related SIRT6/NLRP3 signaling pathway.

Language: Английский

Citations

1
Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis DOI

Huicai Lin,

Zhongyuan Wen,

Linying Feng

et al.

International Journal of Drug Discovery and Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 100025 - 100025

Published: Dec. 17, 2024

Article Ginsenoside Re Alleviates Oxidative Stress Damage and Ferroptosis in Pulmonary Fibrosis Mice by Regulating the Nrf2/Keap1/GPX4 axis Huicai Lin 1,2,3, Zhaoqin Wen Linying Feng Xiaoyan Chen 4, Yongxiang Song 5, Jiang Deng 1,2,3,* 1 Key Laboratory of Basic Pharmacology Ministry Education Joint International Research Ethnomedicine Education, Zunyi Medical University, Zunyi563006, China 2 Guizhou Province, 3 The Second Affiliated Hospital 4 Department Pathophysiology, 5 Thoracic Surgery, * Correspondence: [email protected]; Tel.: +86-851-2864-3411; Fax: +86-851-2864-3411 Received: 30 August 2024; Revised: 28 September Accepted: Published: 17 December 2024 Abstract: fibrosis (PF) is a chronic, progressive, irreversible, fibrotic interstitial lung disease with high mortality. (G-Re) one active components ginseng, which has been proven to possess multiple pharmacological effects, including anti-inflammatory antioxidant. Thus, G-Re considered potential therapeutic agent for treating PF. present study explored protective mechanisms against bleomycin (BLM)-induced PF mice its as strategy A mouse model BLM-induced was utilized assess effect treatment, N-acetylcysteine (NAC) set positive control agent. Various parameters such function, histopathological changes, oxidative stress markers, nuclear factor erythroid 2-related (Nrf2) translocation related protein expressions, Kelch-like ECH-associated (Keap1), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase (NQO-1), ferroptosis signature glutathione peroxidase (GPX4) were evaluated. Continuous administration 14 days significantly reduced injury, enhanced antioxidant capacity, activated Nrf2/Keap1 signaling pathway, inhibited evidenced GPX4. Additionally, treatment collagen deposition, improved pulmonary alleviated tissue mice. These findings demonstrate that exerts effects modulating targeting pathways, highlighting intervention providing insights into molecular underlying effects.

Language: Английский

Citations

1