Targeting the NLRP3 by Natural Compounds: Therapeutic Strategies to Mitigate Doxorubicin-Induced Cardiotoxicity

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

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Therapeutic potential and mechanistic insights of astragaloside IV in the treatment of arrhythmia: a comprehensive review

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

Published: April 10, 2025

Arrhythmia, a common cardiovascular disorder, results from disturbances in cardiac impulse generation and conduction, leading to decreased output myocardial oxygenation, with potentially life-threatening consequences. Despite advancements therapeutic approaches, the incidence mortality associated arrhythmia remain high, drug-related adverse effects continue pose significant challenges. Traditional Chinese Medicine (TCM) has attracted considerable attention for its potential as complementary alternative approach treating diseases, including arrhythmia. Astragalus, prominent herb TCM, is commonly used clinical practice multi-faceted properties, encompassing anti-arrhythmic, cardiotonic, anti-inflammatory, immunomodulatory effects. Astragaloside IV, primary active compound Astragalus membranaceus, demonstrated cardioprotective through mechanisms such antioxidant, anti-apoptotic activities. Although evidence suggests that astragaloside IV holds promise treatment, comprehensive reviews of specific applications are scarce. This review systematically explores pharmacological properties underlying treatment. Utilizing targeted search databases PubMed, Web Science, Cochrane Library, Embase, CNKI, Wanfang Data, we summarize recent findings examine IV's prevention Our analysis aims provide theoretical foundation development novel treatment strategies, while offering insights into future research directions application.

Language: Английский

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NLRP3 inflammasome as a therapeutic target in doxorubicin-induced cardiotoxicity: role of phytochemicals

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

Published: April 17, 2025

Doxorubicin (DOX) has received widespread attention as a broad-spectrum antitumor drug. However, it been recognized challenge that long-term DOX injections can lead to severe cardiotoxicity. There are numerous interventions DOX-induced cardiotoxicity, and the most cost-effective is phytochemicals. It reported phytochemicals have complex diverse biological properties, facilitating mitigation of cardiotoxicity pathological mechanisms, nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis one them. This review initially presents an overview mechanisms underlie induced by DOX. Subsequently, we present comprehensive elucidation structure activation NLRP3 inflammasome. Finally, provide detailed summary mitigate influencing expression inflammasome in cardiomyocytes.

Language: Английский

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Anti-fibrosis effect of astragaloside IV in animal models of cardiovascular diseases and its mechanisms: a systematic review

Pharmaceutical Biology, Journal Year: 2025, Volume and Issue: 63(1), P. 250 - 263

Published: April 22, 2025

Myocardial fibrosis is a common manifestation of end-stage cardiovascular disease, but there lack means to reverse fibrosis. Astragaloside IV (AS-IV), the major active component Astragalus membranaceus Fisch. ex Bunge Fabaceae, possesses diverse biological activities that have beneficial effects against disease. This systematic review aims summarize anti-fibrosis effect AS-IV in animal models (rats or mice only) and its underlying mechanisms, provide potential directions for clinical use AS-IV. PubMed, EMBASE, Web Science, CNKI, Wanfang database, SinoMed were searched from inception 31 December 2024. The following characteristics included studies extracted summarized: model, route administration, dose/concentration, measurement indicators, mechanisms. quality was assessed used 10-item scale SYRCLE. represents promising multi-target candidate myocardial treatment 24 eligible analysis. first comprehensively evaluate mechanisms across heterogeneous disease models, including infarction, hypertension, ischemia-reperfusion injury, myocarditis. may include collagen metabolism, anti-apoptosis, anti-inflammation and, pyroptosis, antioxidants, improving mitochondrial function, regulating senescence, etc. Current evidence remains preclinical, with critical gaps toxicological profiles, human safety thresholds, adverse reaction data. Future research must integrate robust evaluations, optimized combination therapies, adaptive trials validate translational potential.

Language: Английский

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Recent pharmacological advances in the treatment of cardiovascular events with Astragaloside IV

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115752 - 115752

Published: Oct. 22, 2023

Cardiovascular disease (CVD) remains the leading cause of death and disability globally. A wide range CVDs have been reported, each which diverges significantly, exhibiting sophisticated types pathogenesis (e.g., inflammatory, oxidative stress, disorders in cardiomyocyte metabolism). Compared with conventional treatments modern medicine, traditional Chinese medicine (TCM) can exhibit comparative advantages treatment CVDs. TCM be utilized to develop effective strategies for addressing challenges CVD, fewer side effects higher therapeutic efficiency. Astragaloside IV (AS-IV) has confirmed as one major active ingredients found Astragalus membranaceus (a herbal that extensively employed clinically CVDs). Since recent studies shown AS-IV CVD achieved promising results, substance aroused great attention further discussions field. The present review aims summarize pharmacological advances employing

Language: Английский

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Synergistic approach to combat triple-negative breast cancer: Ti3C2/TiO2-based photothermal therapy combined with sonodynamic effect for tumor ablation

Ceramics International, Journal Year: 2023, Volume and Issue: 50(4), P. 6042 - 6054

Published: Nov. 25, 2023

Language: Английский

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Xinfeng Capsule Inhibits Pyroptosis and Ameliorates Myocardial Injury in Rats with Adjuvant Arthritis via the GAS5/miR-21/TLR4 Axis

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2421 - 2433

Published: June 1, 2024

Purpose: This study probed the mechanism of action Xinfeng Capsule (XFC) in myocardial injury rats with adjuvant arthritis (AA) via growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis. Methods: Rats were injected Freund's complete to establish a rat model AA. Then, some modeled given normal saline or drugs only, and adeno-associated viruses necrosulfonamide (NSA; pyroptosis inhibitor) before drug administration. Toe swelling index (AI) calculated. Pathological morphological changes synovial tissues analyzed hematoxylin-eosin staining, pyroptotic vesicles ultrastructural observed transmission electron microscopy. The serum levels interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor (TNF)-α detected, lactate dehydrogenase (LDH) release was measured tissues, accompanied by examination GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like protein 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD) expression tissues. Results: After AA modeling, presented significantly increased toe AI scores, tissue damage, elevated vesicles, markedly enhanced IL-1β, TNF-α, diminished GAS5 expression, substantially augmented NF-κB NLRP3, GSDMD greatly LDH XFC treatment declined swelling, TNF-α rats. Additionally, lowered Moreover, above effects further promoted overexpression NSA treatment. Conclusion: alleviated regulating GAS5/miR-21/TLR4 axis inhibiting pro-inflammatory cytokine secretion. Keywords: arthritis, injury, axis, pyroptosis,

Language: Английский

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A Combination of Astragaloside IV and Hydroxysafflor Yellow A Attenuates Cerebral Ischemia-Reperfusion Injury via NF-κB/NLRP3/Caspase-1/GSDMD Pathway

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(8), P. 781 - 781

Published: July 31, 2024

Cerebral ischemia-reperfusion injury (IRI), occurring after blood supply restoration, contributes significantly to stroke-related deaths. This study explored the combined impact and mechanisms of astragaloside IV (AS-IV), hydroxysafflor yellow A (HSYA), their combination in mitigating IRI. Male Sprague-Dawley (SD) rats were randomized Sham, MCAO, MCAO+AS-IV, MCAO+HSYA, MCAO+AS-IV+HSYA groups. Neurological deficits cerebral infarction examined restoring brain. Pathomorphological changes cortex observed via HE staining. IL-1β IL-18 quantified using ELISA. The expression NF-κB GSDMD ischemic cerebrum was analyzed immunohistochemistry. levels NLRP3, ASC, IL-1β, Caspase-1, evaluated Western blot. groups exhibited notably better neurological function compared with MCAO group. treatment demonstrated superior brain tissue alleviation. Reductions NF-κB, positive cells, NLRP3/ASC/IL-1β/Caspase-1/GSDMD protein more pronounced therapy, indicating a synergistic effect countering IRI NF-κB/NLRP3/Caspase-1/GSDMD pathway inhibition cell pyroptosis-induced injury.

Language: Английский

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Astragaloside IV Inhibits the Pyroptosis in the Acute Kidney Injury through Targeting the SIRT1/FOXO3a Axis

Chemical and Pharmaceutical Bulletin, Journal Year: 2024, Volume and Issue: 72(10), P. 923 - 931

Published: Oct. 29, 2024

Acute kidney injury (AKI) is a commonly encountered critical condition in clinical settings, often resulting from sepsis, infections or ischemia. Astragaloside IV (AS-IV) the primary active component of Astragalus. The functions Astragalus are mainly related to AS-IV, showing remarkable therapeutic effects anti-inflammatory, antioxidant, immune-enhancing, and anti-tumor aspects. This study aimed explore role AS-IV AKI development. Lipopolysaccharide (LPS) was used stimulate HK-2 cells rats establish model vivo vitro. After treatment, cell viability, pyroptosis rate, lactate dehydrogenase (LDH) activity, interleukin (IL)-18 IL-1β contents, cleaved-caspase-1, GSDMD-N, SIRT, FOXO3a protein levels were detected. Caspase-1 analyzed by immunofluorescence staining. Additionallly, acetylation detected immunoprecipitation Western blot assays. treatment promoted inhibited pyroptosis, LDH caspase-1 LPS stimulated cells. decreased IL-18 cleaved-caspase-1 GSDMD-N both rats. Furthermore, after EX527 Sirtuin 1 (SIRT1) inhibitor, reversed. increased FOXO3a, which reversed treatment. Co-immunoprecipitation (CO-IP) assay staining confirmed that SIRT1 interacted with FOXO3a. In conclusion, this research demonstrated occurrence may be mediated deacetylation

Language: Английский

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Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1729 - 1729

Published: Sept. 7, 2023

The role of inflammation and immunity in the pathomechanism neurodegenerative diseases has become increasingly relevant within past few years. In this context, NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial activation inflammatory responses by promoting maturation secretion pro-inflammatory cytokines such as interleukin-1β interleukin-18. We hypothesized that interplay between nuclear factor erythroid 2-related 2 (Nrf2) NADPH oxidase 4 (NOX4) may play critical NLRP3 subsequent responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated ATP, showing significant reduction IL1-β release NOX4 Nrf2 KO mice. Importantly, inhibition using GKT136901 also reduced IL-1β release, cultures. Moreover, we measured expression wild-type following LPS treatment, observing both increased after TLR4 activation, while 24 h treatment tert-butylhydroquinone, potent inducer, significantly expression. administration resulted cognitive impairment compared to control group. Indeed, modified mouse hippocampus. However, mice treated showed improved discrimination index recovered genes normal levels animals. Hence, here validate key player suggesting pharmacological therapeutic approach diseases.

Language: Английский

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