Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway DOI Creative Commons
Ze Li,

Pu Cheng,

Huifeng Xi

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6313 - 6329

Published: Dec. 1, 2024

Intervertebral disc degeneration (IDD) is a leading cause of low back pain, and developing new molecular drugs targets for IDD direction future treatment strategies. The aim this study to investigate the effects mechanisms tomatidine in ameliorating lumbar IDD. Nucleus pulposus cells (NPCs) exposed lipopolysaccharides were used as an vitro model changes expression extracellular matrix components associated signaling pathway molecules. A instability was simulate Tomatidine (Td) then administered intraperitoneally, its evaluated through histopathological analysis. In vitro, Td significantly promoted ECM anabolism, inhibited catabolism, reduced oxidative stress ferroptosis LPS-stimulated NPCs. When Nrf2 inhibited, exacerbated, protective on NPCs lost, suggesting Nrf2/HO-1/GPX4 axis critical therapeutic Td. vivo, analysis demonstrated that ameliorated murine model. alleviates vivo by activating inhibit This mechanism suggests promising candidate treatment.

Language: Английский

KAE ameliorates LPS-mediated acute lung injury by inhibiting PANoptosis through the intracellular DNA-cGAS-STING axis DOI Creative Commons

Yonghu Chen,

Xilin Wu, Zhe Jiang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Acute lung injury (ALI) is a severe condition characterized by inflammation, tissue damage, and persistent activation of the cyclic GMP-AMP (cGAS)-stimulator interferon genes (STING) pathway, which exacerbates production pro-inflammatory mediators promotes progression ALI. Specific inhibition this pathway has been shown to alleviate ALI symptoms. Kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE), an active compound found in flowers Angelica acutiloba Kitagawa, exhibits anti-inflammatory antioxidant properties. This study aimed investigate molecular mechanisms through KAE regulates cGAS-STING context was induced using LPS. Lung damage anti-inflammatory/antioxidant effects were assessed H&E staining, edema index, SOD, MDA, ELISA assays. NO release mitochondrial membrane potential (MMP) measured JC-1 Griess methods. The impact on PANoptosis analyzed flow cytometry, Western blot, immunofluorescence. significantly alleviated lipopolysaccharide-induced pulmonary reducing inflammatory cell infiltration, alleviating edema, enhancing capacity, decreasing levels cytokines mouse tissues. In both vitro vivo analyses, downregulated expression key components including cGAS, STING, p-TBK1, nuclear factor-κB. also reduced assembly PANoptosome, thereby attenuating apoptosis, necroptosis, pyroptosis. Additionally, inhibited cGAS restoring MMP, cytosolic DNA. improve inhibiting DNA suppressing activation, protecting cells from PANoptosis. Our findings provide valuable insights for development application novel therapeutic strategies

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

0
Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols DOI Creative Commons

Annamaria Russo,

Stefano Putaggio,

Ester Tellone

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(6), P. 1211 - 1211

Published: March 8, 2025

Neurodegenerative diseases are a group of that share common features, such as the generation misfolded protein deposits and increased oxidative stress. Among them, amyotrophic lateral sclerosis (ALS), whose pathogenesis is still not entirely clear, complex neurodegenerative disease linked both to gene mutations affecting different proteins, superoxide dismutase 1, Tar DNA binding 43, Chromosome 9 open frame 72, Fused in Sarcoma, altered iron homeostasis, mitochondrial dysfunction, stress, impaired glutamate metabolism. The purpose this review highlight molecular targets ALS ferroptosis. Indeed, many pathways implicated hallmarks ferroptosis, recently discovered type iron-dependent programmed cell death characterized by reactive oxygen species (ROS) lipid peroxidation. Iron accumulation results dysfunction levels ROS, peroxidation, ferroptosis triggers; addition, inhibition Xc− system reduced cystine accumulation, leading excitotoxicity GPx4 synthesis. These potential involvement ALS, providing new biochemical could be exploited treatment using polyphenols.

Language: Английский

Citations

0
METTL3 promotes infantile pneumonia-induced lung injury by the m6A-TBL1XR1-ACSL1 axis DOI

Fuxing Song,

Fang Guo, Bo Su

et al.

Cellular Immunology, Journal Year: 2025, Volume and Issue: 411-412, P. 104944 - 104944

Published: March 16, 2025

Language: Английский

Citations

0
Mechanisms and potential roles of active ingredients of traditional Chinese medicine in the treatment of chronic obstructive pulmonary disease DOI

Xilin Wu,

Yonghu Chen,

Hanyu Zhang

et al.

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

Published: May 12, 2025

Abstract Objectives Chronic obstructive pulmonary disease (COPD) is a respiratory condition with high rates of morbidity and mortality. Recent studies have shown that the increasing research on Traditional Chinese Medicine (TCM) also plays an important role in COPD. The purpose this review to categorize TCM its active ingredients summarize their pharmacological effects. Methods Articles published up December 2024 were searched through PubMed, X-MOL, China National Knowledge Infrastructure. keywords included combination COPD, pharmacologic activity, anti-inflammatory effects, pharmacology, as well vivo vitro studies. Key findings Thus far, we summarized progress mechanisms action ingredients, such flavonoids, terpenoids, phenols, treatment These encompass reduction inflammatory responses lung injury, regulation oxidation-antioxidation balance, modulation cellular apoptosis aging, among other Conclusion demonstrate strong anti-COPD properties. This provides reference for accelerating development herbal components COPD exploring new potential multi-target therapeutic mechanisms. will mitigate geographical limitations using enhance application future management strategies.

Language: Английский

Citations

0
Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species DOI Creative Commons
Waleed Yousuf, Nimra Zafar Siddiqui,

P. Ali

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 698 - 698

Published: May 12, 2025

Dauricine has been shown to possess intriguing anti-cancerous activities against various malignancies. The current study examined the inhibitory effects of dauricine lung adenocarcinoma with cell lines and animal models. MTT assay was performed in three different using a concentration range dauricine. Colony formation, wound healing, Edu incorporation, cycle analysis were conducted investigate impact on cells vitro. Moreover, flow cytometry observe effect cellular ROS levels. expression redox regulator Nrf2 apoptosis-related markers assessed by Western blot. Importantly, anti-tumor efficacy studied vivo two models, including subcutaneous line-derived syngeneic model an inducible orthotopic KRASG12D-driven model. proliferation migration significantly reduced treatment. Flow revealed that treatment resulted arrest at G0/G1 phases A549, H1299, A427 cells. Intracellular levels markedly augmented Notably, led downregulation master Nrf2. Meanwhile, decreased Bcl-2 but elevated BAX cleaved Caspase 3. Finally, demonstrated significant restricting tumor progression both Our results corroborate anti-cancer vitro analyses. findings also provide mechanistic evidence links blockage ROS-mediated apoptosis.

Language: Английский

Citations

0
Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway DOI Creative Commons
Ze Li,

Pu Cheng,

Huifeng Xi

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6313 - 6329

Published: Dec. 1, 2024

Intervertebral disc degeneration (IDD) is a leading cause of low back pain, and developing new molecular drugs targets for IDD direction future treatment strategies. The aim this study to investigate the effects mechanisms tomatidine in ameliorating lumbar IDD. Nucleus pulposus cells (NPCs) exposed lipopolysaccharides were used as an vitro model changes expression extracellular matrix components associated signaling pathway molecules. A instability was simulate Tomatidine (Td) then administered intraperitoneally, its evaluated through histopathological analysis. In vitro, Td significantly promoted ECM anabolism, inhibited catabolism, reduced oxidative stress ferroptosis LPS-stimulated NPCs. When Nrf2 inhibited, exacerbated, protective on NPCs lost, suggesting Nrf2/HO-1/GPX4 axis critical therapeutic Td. vivo, analysis demonstrated that ameliorated murine model. alleviates vivo by activating inhibit This mechanism suggests promising candidate treatment.

Language: Английский

Citations

0