RESUMEN
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
Asunto(s)
Quercetina , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Animales , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hepatopatías/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/lesiones , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/químicaRESUMEN
INTRODUCTION: Understanding the interactions between administered nanoparticles and the liver is crucial for developing safe and effective nanomedicines. As the liver can sequester up to 99% of these particles due to its major phagocytic role, understanding these interactions is vital for clinical translation. AREAS COVERED: This review highlights recent studies on nanoparticle-liver interactions, including the influence of nanoparticle physicochemical properties on delivery, strategies to enhance delivery efficiency by modulating liver Kupffer cells, and their potential for treating certain hepatic diseases. Additionally, we discuss how aging impacts the liver's phagocytic functions. EXPERT OPINION: While liver accumulation can hinder nanomedicine safety and effectiveness, it also presents opportunities for treating certain liver diseases. A thorough understanding of nanoparticle-liver interactions is essential for advancing the clinical application of nanomedicines.
Asunto(s)
Sistemas de Liberación de Medicamentos , Macrófagos del Hígado , Hepatopatías , Hígado , Nanomedicina , Nanopartículas , Humanos , Animales , Hígado/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Macrófagos del Hígado/metabolismo , Envejecimiento , FagocitosisRESUMEN
The prevention and treatment of liver disease, a class of disease that seriously threatens human health, has always been a hot topic of medical research. In recent years, with the in-depth exploration of marine resources, marine natural products have shown great potential and value in the field of liver disease treatment. Compounds extracted and isolated from marine natural products have a variety of biological activities such as significant antiviral properties, showing potential in the management of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), protection of the liver from fibrosis, protection from liver injury and inhibition of the growth of hepatocellular carcinoma (HCC). This paper summarizes the progress of research on marine natural products for the treatment of liver diseases in the past decade, including the structural types of active substances from different natural products and the mechanisms underlying the modulation of different liver diseases and reviews their future prospects.
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Organismos Acuáticos , Productos Biológicos , Hepatopatías , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Productos Biológicos/química , Humanos , Animales , Hepatopatías/tratamiento farmacológico , Antivirales/farmacología , Antivirales/químicaRESUMEN
INTRODUCTION: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease. AREAS COVERED: This review explores current therapeutic options for CF-associated liver disease, presenting ongoing studies and new insights into parthenogenesis for potential future therapies. EXPERT OPINION: Monitoring for signs of portal hypertension is essential. Limited evidence supports ursodeoxycholic acid (UDCA) efficacy in halting CF liver disease progression. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on liver outcomes lacks definitive data, since patients with CF-related liver disease were excluded from trials due to potential hepatotoxicity. A proposed approach involves using UDCA and modulators in early stages, along with anti-inflammatory agents, with further therapeutic strategies awaiting randomized trials. Prevention of portal hypertensive bleeding includes endoscopic sclerotherapy or ligation of esophageal varices. Nonselective beta-blockers may also prevent bleeding and could be cautiously implemented. Other non-etiological treatments require investigation.
Asunto(s)
Fibrosis Quística , Hipertensión Portal , Humanos , Hipertensión Portal/fisiopatología , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/etiología , Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Fibrosis Quística/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico , Hepatopatías/fisiopatología , Hepatopatías/terapia , Hepatopatías/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Várices Esofágicas y Gástricas/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Calidad de Vida , Progresión de la EnfermedadRESUMEN
Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO-decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.
Asunto(s)
Antioxidantes , Diabetes Mellitus Experimental , Euphausiacea , Ferroptosis , Factor 2 Relacionado con NF-E2 , Aceites , Animales , Euphausiacea/química , Antioxidantes/farmacología , Ferroptosis/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Aceites/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Ratones , Ácidos Grasos Omega-3/farmacología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Expresión Génica/efectos de los fármacos , Hepatopatías/etiología , Hepatopatías/prevención & control , Hepatopatías/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/patologíaRESUMEN
Increasing evidence indicates that disturbance of the clock genes, which leads to systemic endocrine perturbation, plays a crucial role in the pathogenesis of metabolic and liver diseases. Fluorene-9-bisphenol (BHPF) is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown. The impacts and involved mechanisms of BHPF on the liver diseases, metabolism, and circadian clock were comprehensively studied by zebrafish and mouse models. The therapeutic effect of melatonin (MT) was also verified. Zebrafish and mouse models with either acute exposure (0.5 and 1 µmol/L, 1-4 days post-fertilization) or chronic oral exposure (0.5 and 50 mg/(kg·2 days), 30 days) were established with various BHPF concentrations. Herein, we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model. BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain. The liver sexual dimorphic alteration along with reduced growth hormone and estrogens played a critical role in damaged glucose metabolism, hepatic inflammation, and fibrosis induced by BHPF. Besides, sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice. We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for liver metabolism disorders associated with endocrine perturbation chemicals. These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.
Asunto(s)
Ritmo Circadiano , Fluorenos , Pez Cebra , Animales , Ratones , Fluorenos/toxicidad , Ritmo Circadiano/efectos de los fármacos , Hepatopatías/tratamiento farmacológico , Fenoles/toxicidadRESUMEN
Macrophages, as important immune cells of the organism, are involved in maintaining intrahepatic microenvironmental homeostasis and can undergo rapid phenotypic changes in the injured or recovering liver. In recent years, the crucial role of macrophage-programmed cell death in the development and regression of liver diseases has become a research hotspot. Moreover, macrophage-targeted therapeutic strategies are emerging in both preclinical and clinical studies. Given the macrophages' vital role in complex organismal environments, there is tremendous academic interest in developing novel therapeutic strategies that target these cells. This review provides an overview of the characteristics and interactions between macrophage polarization, programmed cell death, related biomarkers, and macrophage-targeted therapies. It aims to deepen the understanding of macrophage immunomodulation and molecular mechanisms and to provide a basis for the treatment of macrophage-associated liver diseases.
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Biomarcadores , Hepatopatías , Macrófagos , Humanos , Hepatopatías/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/inmunología , Hepatopatías/terapia , Macrófagos/metabolismo , Macrófagos/inmunología , Biomarcadores/metabolismo , Animales , Apoptosis/efectos de los fármacos , Terapia Molecular DirigidaRESUMEN
The Hedgehog (Hh) signaling plays a crucial role in adult liver repair by promoting the expansion and differentiation of hepatic progenitor cells into mature hepatocytes and cholangiocytes. Elevated Hh signaling is associated with severe chronic liver diseases, making Hh inhibitors a promising therapeutic option. Sonidegib and vismodegib, both FDA-approved Smoothened (Smo) inhibitors for basal cell carcinoma (BCC), have shown potential for application in chronic liver disorders based on clinical evidence. We highlight the vital role of the Hh pathway in metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC). Moreover, therapeutic strategies targeting the Hh pathway in chronic liver diseases have been discussed, providing a basis for improving disease management and outcomes.
Asunto(s)
Proteínas Hedgehog , Hepatopatías , Transducción de Señal , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Hepatopatías/metabolismo , Hepatopatías/tratamiento farmacológico , Enfermedad Crónica , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismoRESUMEN
BACKGROUND: Economic hardship associated with chronic liver disease (CLD) may delay timely access to healthcare. AIM: To estimate the national burden of financial hardship across the spectrum of CLD in the United States (US) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A cross-sectional analysis was performed using the 2020-2021 US National Health Interview Survey database. The questionnaire defined financial hardship from medical bills and cost-related nonadherence to medications in patients with CLD. We used weighted survey analysis to obtain the national estimates. RESULTS: While 6.9% (95% confidence interval [CI]: 6.7%-7.2%) out of 60,689 US adults (weighted sample: 251 million) reported financial hardship and inability to pay medical bills; 10.6% (95% CI: 8.3%-13.4%), 18.2% (95% CI: 14.5%-22.6%), 22.6% (95% CI: 11.0%-41.0%) with hepatitis, CLD/cirrhosis, and liver cancer experienced an inability to pay their medical bills due to financial hardship, respectively. 19.8% (95% CI: 15.9%-24.5%) and 23.3% (95% CI: 12.5%-39.3%) with CLD/cirrhosis and liver cancer, respectively experienced cost-related nonadherence to medications, compared to a tenth of US adults (10.7%, 95% CI: 10.3%-11.2%). CLD/cirrhosis demonstrated an independent association with financial hardship from medical bills and cost-related nonadherence to medications. Overall, these disparities were more pronounced in individuals aged <65 years old. In addition, over 40% of individuals with CLD/cirrhosis reported difficulties accessing medical care during the COVID-19 pandemic. CLD/cirrhosis showed an independent association with difficulties accessing medical care due to COVID-19. CONCLUSIONS: Financial hardship from medical bills and cost-related nonadherence to medication can negatively impact individuals with CLD and need further evaluation.
Asunto(s)
COVID-19 , Estrés Financiero , Hepatopatías , Cumplimiento de la Medicación , Humanos , Estados Unidos , Cumplimiento de la Medicación/estadística & datos numéricos , Estudios Transversales , Masculino , Femenino , COVID-19/economía , COVID-19/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Hepatopatías/economía , Hepatopatías/tratamiento farmacológico , Costo de Enfermedad , SARS-CoV-2 , Adulto Joven , Adolescente , Enfermedad Crónica/tratamiento farmacológico , Gastos en Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/economíaRESUMEN
Aim Hepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats. MAIN METHODS: HIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation. The biochemical and histopathological investigations, in addition to the mechanistic characterizations of the effect of the tested drugs were performed. KEY FINDINGS: HIRI was assured with elevated liver enzymes and marked changes in histopathological features, inflammatory response and oxidative stress. Pretreatment with Coxi and Voxi improved the hepatic histopathological alterations, reduced the elevated serum liver enzymes level and hepatic Malondialdehyde (MDA) content, increased the hepatic Superoxide Dismutase (SOD) activity and reduced Glutathione (GSH) content, downregulated the expression of TNF-α, IL-6, Nod-Like Receptor p3 (NLRP3), Cleaved caspase1, Cleaved caspase 3 proteins, alongside the expression level of IL-1ß, ICAM-1, VCAM-1 and BAX genes, attenuated NF-кB p-P65 Ser536 and Myeloperoxidase (MPO)-positive neutrophils, and activated the PI3K/AKT pathway. SIGNIFICANCE: Coxi and Voxi have promising hepatoprotective activity against HIRI in rats through ameliorating the biochemical and histopathological alterations, attenuating inflammatory and oxidative stress status by modulating the inflammatory TNF-α/ICAM-1, the pyroptosis NLRP3/Caspase-1, and the antioxidant PI3K/AKT pathways.
Asunto(s)
Caspasa 1 , Modelos Animales de Enfermedad , Hígado , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Oxindoles , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Wistar , Daño por Reperfusión , Transducción de Señal , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Oxindoles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Transducción de Señal/efectos de los fármacos , Caspasa 1/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hepatopatías/metabolismo , Hepatopatías/prevención & control , Hepatopatías/patología , Hepatopatías/tratamiento farmacológicoRESUMEN
Nuclear receptors (NRs) are ligand-dependent transcription factors required for liver development and function. As a consequence, NRs have emerged as attractive drug targets in a wide range of liver diseases. However, liver dysfunction and failure are linked to loss of hepatocyte identity characterised by deficient NR expression and activities. This might at least partly explain why several pharmacological NR modulators have proven insufficiently efficient to improve liver functionality in advanced stages of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this perspective, we review the most recent advances in the hepatic NR field and discuss the contribution of multiomic approaches to our understanding of their role in the molecular organisation of an intricated transcriptional regulatory network, as well as in liver intercellular dialogues and interorgan cross-talks. We discuss the potential benefit of novel therapeutic approaches simultaneously targeting multiple NRs, which would not only reactivate the hepatic NR network and restore hepatocyte identity but also impact intercellular and interorgan interplays whose importance to control liver functions is further defined. Finally, we highlight the need of considering individual parameters such as sex and disease stage in the development of NR-based clinical strategies.
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Hepatopatías , Receptores Citoplasmáticos y Nucleares , Humanos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/fisiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/fisiopatología , Hepatopatías/metabolismo , Hepatocitos/metabolismo , Hígado/metabolismo , Hígado/fisiopatologíaRESUMEN
INTRODUCTION: Chronic liver disease (CLD) is a complex disease associated with profound dysfunction. Despite an incredible burden, the first and only pharmacotherapy for metabolic-associated steatohepatitis was only approved in March of this year, indicating a gap in the translation of preclinical studies. There is a body of preclinical work on the application of phosphodiesterase 4 inhibitors in CLD, none of these molecules have been successfully translated into clinical use. AREAS COVERED: To design therapies to combat CLD, it is essential to consider the dysregulation of other tissues that contribute to its development and progression. As such, proper therapies must combat this throughout the body rather than focusing only on the liver. To detail this, literature characterizing the pathogenesis of CLD was pulled from PubMed, with a particular focus placed on the role of PDE4 in inflammation and metabolism. Then, the focus is shifted to detailing the available information on existing PDE4 inhibitors. EXPERT OPINION: This review gives a brief overview of some of the pathologies of organ systems that are distinct from the liver but contribute to disease progression. The demonstrated efficacy of PDE4 inhibitors in other human inflammatory diseases should earn them further examination for the treatment of CLD.
Asunto(s)
Tejido Adiposo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Inhibidores de Fosfodiesterasa 4 , Humanos , Inhibidores de Fosfodiesterasa 4/farmacología , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacos , Hepatopatías/tratamiento farmacológico , Hepatopatías/fisiopatología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Progresión de la Enfermedad , Enfermedad Crónica , Desarrollo de MedicamentosRESUMEN
Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous impact in guiding future strategies for the prevention and treatment of CLDs.
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Biomarcadores , Sistemas de Liberación de Medicamentos , Hepatopatías , Humanos , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Animales , Sistemas de Liberación de Medicamentos/métodos , Enfermedad Crónica , Nanopartículas , Sistema de Administración de Fármacos con NanopartículasRESUMEN
BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.
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Hígado , Fitoquímicos , Daño por Reperfusión , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Humanos , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Hepatopatías/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Excessive fat accumulation, biological clock dysregulation, viral infections, and sustained inflammatory responses can lead to liver inflammation, fibrosis, and cancer, thus promoting the development of chronic liver disease. A comprehensive understanding of the etiological factors leading to chronic liver disease and the intrinsic mechanisms influencing its onset and progression can aid in identifying potential targets for targeted therapy. Mitochondria, as key organelles that maintain the metabolic homeostasis of the liver, provide an important foundation for exploring therapeutic targets for chronic liver disease. Recent studies have shown that active ingredients in herbal medicines and their natural products can modulate chronic liver disease by influencing the structure and function of mitochondria. Therefore, studying how Chinese herbs target mitochondrial structure and function to treat chronic liver diseases is of great significance. AIM OF THE STUDY: Investigating the prospects of herbal medicine the Lens of chronic liver disease based on mitochondrial structure and function. MATERIALS AND METHODS: A computerized search of PubMed was conducted using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "botanicals, mitochondria and chronic liver disease".Data from the Web of Science and Science Direct databases were also included. The research findings regarding herbal medicines targeting mitochondrial structure and function for the treatment of chronic liver disease are summarized. RESULTS: A computerized search of PubMed using the keywords "mitochondrial structure", "mitochondrial function", "mitochondria and chronic liver disease", "phytopharmaceuticals, mitochondria, and chronic liver disease", as well as the Web of Science and Science Direct databases was conducted to summarize information on studies of mitochondrial structure- and function-based Chinese herbal medicines for the treatment of chronic liver disease and to suggest that the effects of herbal medicines on mitochondrial division and fusion.The study suggested that there is much room for research on the influence of Chinese herbs on mitochondrial division and fusion. CONCLUSIONS: Targeting mitochondrial structure and function is crucial for herbal medicine to combat chronic liver disease.
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Medicamentos Herbarios Chinos , Hepatopatías , Mitocondrias , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Enfermedad Crónica , Medicina Tradicional China/métodos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/patologíaAsunto(s)
Inmunodeficiencia Variable Común , Fiebre , Hepatopatías , Hígado , Esplenomegalia , Anciano , Humanos , Masculino , Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/etiología , Médula Ósea/patología , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/terapia , Diagnóstico Diferencial , Enfermedades del Sistema Digestivo/diagnóstico , Enfermedades del Sistema Digestivo/diagnóstico por imagen , Enfermedades del Sistema Digestivo/tratamiento farmacológico , Enfermedades del Sistema Digestivo/etiología , Progresión de la Enfermedad , Fiebre/etiología , Granuloma/diagnóstico por imagen , Granuloma/tratamiento farmacológico , Granuloma/etiología , Hígado/patología , Hígado/diagnóstico por imagen , Hepatopatías/diagnóstico por imagen , Hepatopatías/tratamiento farmacológico , Hepatopatías/etiología , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/tratamiento farmacológico , Nódulos Pulmonares Múltiples/etiología , Recurrencia , Fiebre Recurrente/diagnóstico , Fiebre Recurrente/tratamiento farmacológico , Fiebre Recurrente/etiología , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/etiología , Tomografía Computarizada por Rayos XRESUMEN
Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedad Crónica , Neoplasias Hepáticas/prevención & control , Carcinoma Hepatocelular/prevención & control , Hepatopatías/tratamiento farmacológico , Animales , Resultado del TratamientoRESUMEN
SCOPE: Liver injury is a major complication associated with sepsis. Together with others, the study has shown that gallic acid (GA) exerts anti-inflammatory and antioxidant effects in vivo. However, the role of GA in sepsis-mediated hepatic impairment and the underlying mechanisms remains to be elucidated. METHODS AND RESULTS: C57BL/6J mice are pretreated with saline or GA and subjected to sham or cecal ligation and puncture (CLP). The pathological alterations are assessed by hematoxylin and eosin staining as well as immunohistochemical staining. RNA sequencing is employed to analyze hepatic transcriptome modifications. The study finds that GA supplementation significantly ameliorates CLP-induced mortality, liver dysfunction, and inflammation. RNA sequencing reveals that 1324 genes are markedly differentially regulated in livers of saline- or GA-treated sham or CLP mice. Gene ontology analysis demonstrates that the differentially expressed genes regulated by GA are predominantly correlated with the immune system process, oxidation-reduction process, and inflammatory response. Furthermore, mitogen-activated protein kinase (MAPK) signaling is localized in the center of the GA-mediated pathway network. Notably, activation of MAPK by C16-PAF significantly blocks GA-mediated protective effects on hepatic injury, inflammation, as well as CCAAT/enhancer-binding protein-ß (C/EBPß) dependent extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling. CONCLUSION: Therefore, this study indicates that GA may offer a promising therapeutic opportunity for sepsis-associated liver injury.
Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT , Ácido Gálico , Hígado , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , Sepsis , Animales , Ácido Gálico/farmacología , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/genética , Masculino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Hepatopatías/etiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismoRESUMEN
Liver disease is a serious public health problem worldwide, affecting human health. However, there are still many unmet needs for the treatment of liver disease, especially with new therapeutic drugs. At present, there is no treatment method to eradicate the hepatitis B virus, nor are there therapeutic drugs for liver fibrosis, liver failure, and others. Chemotherapy and targeted immunotherapy are still unsatisfactory for liver cancer. This article provides an overview of the current status and challenges that arise in new drug research and development for liver diseases.