Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: May 16, 2023

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of worldwide. These conditions can lead to cirrhosis, cancer, failure, other related ailments. At present, transplantation remains sole treatment option for end-stage NASH, a rapidly growing socioeconomic burden. Kupffer cells (KCs) dominant population macrophages that reside in liver, playing crucial role innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, triggering immune responses. Moreover, they interact with during pathogenesis NAFLD, this crosstalk may either delay or exacerbate progression. Stimulation by endogenous signals triggers activation KCs, resulting expression various inflammatory factors chemokines, such NLRP3, TNF-α, IL-1B, IL-6, contributing cascade. In past 5 years, significant advances have been made understanding biological properties functions KCs including their interactions tissue molecules, underlying molecular mechanisms, signaling pathways, relevant therapeutic interventions. Having comprehensive these mechanisms characteristics enormous potential guiding future strategies prevention NAFLD.

Language: Английский

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Parishin A-loaded mesoporous silica nanoparticles modulate macrophage polarization to attenuate tendinopathy

npj Regenerative Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 10, 2023

Macrophages are involved mainly in the balance between inflammation and tenogenesis during healing process of tendinopathy. However, etiological therapeutic strategies to efficiently treat tendinopathy by modulating macrophage state still lacking. In this study, we find that a small molecule compound Parishin-A (PA) isolated from Gastrodia elata could promote anti-inflammatory M2 polarization inhibiting gene transcription protein phosphorylation signal transducers activators 1. Local injection or sustained delivery PA mesoporous silica nanoparticles (MSNs) almost recover native tendon's dense parallel-aligned collagen matrix collagenase-induced macrophage-mediated immune microenvironment preventing heterotopic ossification. Especially, MSNs decrease doses PA, frequency yield preferable effects. Mechanistically, intervention with indirectly inhibit activation mammalian target rapamycin repress chondrogenic osteogenic differentiation tendon stem/progenitor cells influencing inflammatory cytokine secretion. Together, pharmacological natural small-molecule modulate status appears be promising strategy for treatment.

Language: Английский

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Oregano Essential Oil in Livestock and Veterinary Medicine

Animals, Journal Year: 2024, Volume and Issue: 14(11), P. 1532 - 1532

Published: May 22, 2024

With a growing global concern over food safety and animal welfare issues, the livestock veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also opportunities for development. In this context, search natural safe products that can effectively replace traditional drugs has become an important research direction in fields of husbandry medicine. Oregano essential oil (OEO), as extract, is gradually emerging medicine with its unique antibacterial, antioxidant, multiple other biological activities. OEO wide antibacterial spectrum, fighting against variety pathogenic microorganisms, also, because properties, helps us to avoid may bring drug residues or cause resistance problems. This indicates great application potential disease treatment, growth promotion, improvement. At present, achieved preliminary results. Studies shown adding feed significantly improve performance health status animals reduce occurrence disease. same time, pharmacokinetic studies show absorption, distribution, metabolism, excretion processes shows good bioavailability. summary, oregano substitute broad prospects, becoming hotspot field future, we look forward further tapping through more practice making greater contributions sustainable development industries.

Language: Английский

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Aflatoxin-B1-Exposure-Induced Hepatic Injury Could Be Alleviated by Polydatin through Reducing Oxidative Stress, Inhibiting Inflammation and Improving Mitophagy

Toxics, Journal Year: 2023, Volume and Issue: 11(4), P. 309 - 309

Published: March 26, 2023

Aflatoxin B1 (AFB1) is a toxic food/feed pollutant, exerting extensive deleterious impacts on the liver. Oxidative stress and inflammation are considered to be vital contributors AFB1 hepatotoxicity. Polydatin (PD), naturally occurring polyphenol, has been demonstrated protect and/or treat liver disorders caused by various factors through its antioxidant anti-inflammatory properties. However, role of PD in AFB1-induced injury still elusive. Therefore, this study was designed investigate protective effect hepatic mice subjected AFB1. Male were randomly divided into three groups: control, AFB1-PD groups. The results showed that protected against reduced serum transaminase activity, restored histology ultrastructure, which could attributed enhanced glutathione level, interleukin 1 beta tumor necrosis factor alpha concentrations, increased 10 expression at transcriptional level up-regulated mRNA related mitophagy. In conclusion, alleviate reducing oxidative stress, inhibiting improving

Language: Английский

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Insights into the Role of Oxidative Stress in Hepatocellular Carcinoma Development

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(11), P. 286 - 286

Published: Nov. 8, 2023

Oxidative stress (OS) is linked to hepatocellular carcinoma (HCC) progression. HCC may develop as a result of genetic changes, including oxidative injury both nuclear and mitochondrial DNA. Signaling pathways regulated by OS, such Wnt/β-catenin Notch pathways, are vital regulators in developing HCC. OS-mediated activation transcription factors, factor-κB p53, among others, capable regulating the redox state cells. OS also affects tumor microenvironment, which, turn, regulates In HCC, reactive oxygen species (ROS) can potentially enhance cell proliferation, metastasis, resistance treatment. However, elevated ROS levels cause cytotoxicity trigger apoptosis This review highlights explores potential stress-related treatment targets offering novel insights for clinical therapies.

Language: Английский

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Preclinical toxicological assessment of polydatin in zebrafish model

Drug and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 47(6), P. 923 - 932

Published: Feb. 4, 2024

Polydatin (3,4',5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to widespread adoption human therapeutics and consumer products, comprehensive investigation of toxicological effects is crucial. In this study, the toxicity polydatin was investigated developmental test using zebrafish (Danio rerio) as valuable model preclinical assessments. We employed Fish Embryo Test (FET – OECD n°236) investigate on survival, hatchability, development, behavior embryo-larval stage. Remarkably, results demonstrated that up 435 μM showed no toxicity. Throughout exposure period, embryos exposed exhibited normal with significant mortality observed. Furthermore, hatching success heartbeat rate were unaffected, morphological abnormalities identified, signifying lack teratogenic cardiotoxicity. Locomotion activity assessment revealed swimming patterns response stimuli, indicating neurotoxic effects. Our study provides insights into profile polydatin, suggesting it may offer therapeutic benefits under considerable concentration range. addition, proves be an efficient system early-stage screening, guiding further investigations secure utilization wellness.

Language: Английский

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Polydatin retards the progression of osteoarthritis by maintaining bone metabolicbalance and inhibiting macrophage polarization

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 7, 2025

Polydatin (PD), also known as tiger cane glycoside, is a natural compound extracted from the Japanese knotweed plant, which often referred to white resveratrol. It exhibits anti-inflammatory, antioxidant, and anti-apoptotic effects in treatment of various diseases. However, potential molecular mechanisms PD osteoarthritis have not been clearly elucidated. Anterior cruciate ligament transection (ACLT) surgery was performed establish an animal model. Female mice at age 12 weeks were intraperitoneally injected with different concentrations (20 40 mg/kg). In vitro models established by isolating mouse articular chondrocytes, subsequently treated lipopolysaccharide or IL-1β for 24 h subsequent experiments. addition, administered h. Morphological changes observed toluidine blue staining, joint bone metabolism tartrate-resistant acid phosphatase immunohistochemistry used observe expression levels inflammatory factors extracellular matrix. MicroCT analysis conducted assess microstructure subchondral trabeculae, Western blot measure nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) signaling pathway markers M1 polarization macrophages. significantly delays progression induced ACLT, effectively inhibits IL-1β-induced inflammation, metabolic remodeling matrix degradation. paeoniflorin markedly suppresses transmission NF-κB reverses macrophages IL-1β. Taken together, might be therapeutic agent prevention osteoarthritis.

Language: Английский

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Polydatin, a derivative of resveratrol, ameliorates busulfan-induced oligozoospermia in mice by inhibiting NF-κB pathway activation and suppressing ferroptosis

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108170 - 108170

Published: Jan. 16, 2025

Language: Английский

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Polydatin and Nicotinamide Prevent Iron Accumulation and Lipid Peroxidation in Cellular Models of Mitochondrial Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 215 - 215

Published: Feb. 13, 2025

Ferroptosis, an iron-dependent form of non-apoptotic cell death, is regulated by a complex network involving lipid metabolism, iron homeostasis, and the oxidative-reductive system, with accumulation peroxidation as key drivers. Mitochondrial dysfunction ROS overproduction often underlie pathogenesis mitochondrial diseases, for which treatment options are limited, emphasizing need novel therapies. In this study, we investigated whether polydatin nicotinamide could reverse ferroptosis-related pathological features in cellular models derived from patients pathogenic GFM1 variants. Mutant fibroblasts showed increased lipofuscin accumulation, altered expression metabolism-related proteins, elevated peroxidation, heightened susceptibility to erastin-induced ferroptosis. Treatment effectively corrected these alterations reduced induced neurons. Furthermore, chloramphenicol control cells mimicked mutant phenotype, suggesting that changes linked protein synthesis defect characteristic Notably, adding vitamin E co-treatment resulted reduction minimum effective concentration, potential benefits its inclusion. conclusion, combination polydatin, nicotinamide, represent promising therapeutic option disorders caused

Language: Английский

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Polydatin Mitigates Lead-Induced Nephropathy by Modulating Oxidative Stress, Inflammation, and the AMPK/AKT/Nrf2 Pathway in Rats

Biological Trace Element Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

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