Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

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Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 334 - 334

Published: March 10, 2024

Ferroptosis is a recently discovered type of programmed cell death that mechanistically different from other types such as apoptosis, necroptosis, and autophagy. It characterized by the accumulation intracellular iron, overproduction reactive oxygen species, depletion glutathione, extensive lipid peroxidation lipids in membrane. was ferroptosis interconnected with many diseases, neurodegenerative ischemia/reperfusion injury, cancer, chronic kidney disease. Polyphenols, plant secondary metabolites known for bioactivities, are being extensively researched context their influence on which resulted great number publications showing need systematic review. In this review, an literature search performed. Databases (Scopus, Web Science, PubMed, ScienceDirect, Springer) were searched time span 2017 to November 2023, using keyword “ferroptosis” alone combination “flavonoid”, “phenolic acid”, “stilbene”, “coumarin”, “anthraquinone”, “chalcone”; after selection studies, we had 311 papers 143 phenolic compounds. total, 53 compounds showed ability induce ferroptosis, 110 able inhibit out those compounds, 20 both abilities depending model system. The most shikonin, curcumin, quercetin, resveratrol, baicalin. common modes action modulation Nrf2/GPX4 Nrf2/HO-1 axis iron metabolism.

Language: Английский

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Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 153 - 170

Published: Jan. 1, 2024

Purpose: Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and blood vessels, leading impairment of function. Studies on effect capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed investigate specific mechanism which CAP improves LPS-induced ALI. Methods: The present investigated potential underlying mechanisms vitro vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM). TRPV1 inhibitor AMG9810 AKT agonist SC79 were used confirm protective TRPV1/AKT axis against autophagy rapamycin (Rapa) inhibitors 3-methyladenine (3-MA) bafilomycin A1 (Baf-A1) clarify characteristics autophagy. Results: Our findings demonstrated that effectively suppressed inflammation ALI, both vitro. involves regulation signaling pathway. By activating TRPV1, reduces expression P-AKT, thereby exerting its anti-inflammatory inhibitory effects pro-death Furthermore, prior administration provided substantial protection mice induced LPS, reduced wet/dry ratio, decreased proinflammatory cytokine expression, downregulated LC3 expression. Conclusion: Taken together, our results indicate protects inhibiting inflammatory responses autophagic death through pathway, presenting novel strategy for therapy. Keywords: capsaicin, acute injury, Inflammation, autophagy,

Language: Английский

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Review on the pharmacological effects and pharmacokinetics of scutellarein

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(9)

Published: June 7, 2024

Scutellarein is a flavonoid from Scutellaria baicalensis Georgi that has been shown to have variety of pharmacological activities. This review aims summarize the and pharmacokinetic studies on scutellarein provide useful information for relevant scholars. Pharmacological indicate possesses diverse range properties, including but not limited anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, cardiovascular protective effects. Further investigation reveals effects are driven by multiple mechanisms. These mechanisms encompass scavenging free radicals, inhibition activation inflammatory signaling pathways expression mediators, activity crucial viral proteins, suppression gluconeogenesis, amelioration insulin resistance, improvement cerebral ischemia-reperfusion injury, induction apoptosis in cancer cells, prevention myocardial hypertrophy, among others. In summary, these suggest holds promise treatment various diseases. It imperative conduct clinical further elucidate therapeutic scutellarein. However, it worth noting pharmacokinetics reveal an inhibitory effect uridine 5'-diphosphate glucuronide transferases cytochrome P450 enzymes, potentially posing safety risks.

Language: Английский

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Therapeutic effect of phycocyanin on chronic obstructive pulmonary disease in mice

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 66, P. 285 - 301

Published: Jan. 10, 2024

The prevention and treatment of chronic obstructive pulmonary disease (COPD) is closely tied to anti-oxidation anti-inflammation. Phycocyanin (PC) have numerous pharmacological effects such as anti-oxidation, anti-inflammation, so on. But it remains unclear whether PC can play a therapeutic role in COPD. As inflammation oxidative stress aggravate the COPD, this study explore effect on COPD mice its mechanisms. model was established by exposing lipopolysaccharide (LPS) cigarette smoke (CS), administrated concentration 50 mg/kg for 30 days. On last day, lung function measured, bronchoalveolar lavage fluid (BALF) obtained classified cell. Lung tissues pathological change analyzed organ indices statistics were measured. Based molecular docking mechanism explored with Western blotting, immunohistochemical immunofluorescence vivo vitro. significantly ameliorated reduced (p<0.05), Hematoxylin eosin (H&E) showed depressed inflammatory cell accumulation emphysema. Periodic acid Schiff (PAS) Masson staining revealed that retarded goblet cells metaplasia collagen deposition (p<0.05). In addition, regulated Heme oxygenase 1 (HO-1) (p<0.05) NAD(P)H dehydrogenase quinone (NQO1) level (p<0.01) lung, well NOX2 macrophages. Molecular results indicate phycocyanobilin (PCB) had good binding site Keap1 proteins, phycocyanobilin-bound phycocyanin peptide (PCB-PC-peptide) further studies. vitro PCB-PC-peptide could depress phospho-NF-E2-related factor 2 (p-Nrf2) NQO1 protein expression RAW264.7 induced extract (CSE) exerts beneficial via anti-inflammatory anti-oxidative stress, which may be achieved through PCB.

Language: Английский

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Natural flavonoids act as potent ferroptosis inhibitors and their potentials in the treatment of ferroptosis-associated diseases

Pharmacological Research - Modern Chinese Medicine, Journal Year: 2024, Volume and Issue: 10, P. 100377 - 100377

Published: Jan. 26, 2024

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, has been involved in the pathogenesis of various diseases, such as ischemia/reperfusion injury, neurodegenerative and inflammatory disorders. Pharmacological inhibition ferroptosis represents a promising strategy for treatment above diseases. Flavonoids, class natural products found medicinal plants functional foods, are known numerous activities, especially newly discovered anti-ferroptotic activity. Our review aims to expand our understanding flavonoids' activity on multiple biological systems highlight importance utilizing flavonoids ferroptosis-associated A systematic literature search was conducted using Google Scholar, PubMed, Web Science, ScienceDirect, Springer Link. The following keywords: flavonoids, products, ferroptosis, mechanism, available information comprehensively studied compiled. We recent advances molecular mechanisms its roles diverse further systematically summarize inhibitory underlying suggest that ROS accumulation labile Fe2+ availability well activation Nrf2 signaling responsible inhibition. also discuss their clinical applications ferroptosis-related Taken together, exhibit prospect This is expected not only facilitate design development flavonoid-based inhibitors, but diseases therapies.

Language: Английский

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Analysis of network expression and immune infiltration of disulfidptosis‐related genes in chronic obstructive pulmonary disease

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(4)

Published: April 1, 2024

Abstract Background Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays pivotal role in the development of COPD. Disulfidptosis newly discovered type that may be associated with progression However, expression disulfidptosis‐related genes (DRGs) COPD remain unclear. Methods The DRGs was identified by analyzing RNA sequencing (RNA‐seq) data Further, patients were classified into two subtypes unsupervised cluster analysis to reveal their differences gene immune infiltration. Meanwhile, hub disulfidptosis screened weighted co‐expression network analysis. Subsequently, validated experimentally cells animals. In addition, we potential therapeutic drugs through genes. Results We distinct molecular clusters observed significant populations between them. nine genes, experimental validation showed CDC71, DOHH, PDAP1, SLC25A39 significantly upregulated cigarette smoke‐induced mouse lung tissues bronchial epithelial (BEAS‐2B) treated smoke extract. Finally, predicted 10 small molecule such as Atovaquone, Taurocholic acid, Latamoxef, Methotrexate. Conclusion highlighted strong association disulfidptosis, demonstrating discriminative capacity for Additionally, certain novel including SLC25A39, linked aid diagnosis assessment this condition.

Language: Английский

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Scutellarein Inhibits Osteosarcoma Growth by Targeting the TLR4/TRAF6/NF-κB Pathway

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 51 - 64

Published: Jan. 1, 2025

Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) monomeric flavone bioactive compound potent anti-cancer activity. However, effects mechanisms SCU on growth OS remain unknown. The Cell Counting Kit-8, colony formation assay 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to analyze cell proliferation ability in vitro. TLR4/TRAF6/NF-κB signaling transduction was investigated by RNA sequencing analysis, quantitative real-time polymerase chain reaction, Western blotting, NF-κB luciferase reporter assay, immunofluorescent staining, immunoprecipitation. Molecular docking cellular thermal shift employed confirm binding interaction between TLR4. TLR4 overexpression analyzed using xenograft model immunohistochemical staining. found significantly inhibit proliferation, analysis suggested that pathway closely this process. Further studies revealed inhibited canonical through its TLR4, which disrupted TRAF6. Moreover, also repressed signal inhibiting expression. Furthermore, suppress targeting vitro vivo. exhibited dual impact expression disrupting TLR4-TRAF6 interaction, resulting inactivation, thereby blocking growth.

Language: Английский

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Study on the mechanism of Trichosanthes kirilowii Maxim. against COPD based on serum chemical composition analysis, network pharmacology, and experimental study

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156533 - 156533

Published: Feb. 22, 2025

Language: Английский

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LXA4 alleviates inflammation and ferroptosis in cigarette smoke induced chronic obstructive pulmonary disease via the ALX/FPR2 receptor

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114322 - 114322

Published: Feb. 24, 2025

Language: Английский

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