Xuanyu Wu, Xiang Xiao, Yuchen Su, Yuwei Zhang, Ganggang Li, Fei Wang, Quanyu Du, Han Yang
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引用次数: 0
摘要
背景:肺纤维化(Pulmonary fibrosis, PF)是一种与年龄相关的间质性肺疾病,目前缺乏有效的药物治疗。槲皮素已被证明具有良好的抗炎和抗纤维化特性,初步证据表明其在PF患者中的潜在疗效和耐受性。然而,槲皮素对PF模型的保护作用和潜在机制的全面系统综述和评价仍有待完成。因此,我们进行了这项研究。方法:检索截至2024年4月1日的PubMed、Cochrane Library、Embase和Web of Science数据库。CAMARADES是方法学质量评估工具。采用R和Stata 16.0进行统计学分析。采用Origin建立槲皮素治疗前列腺癌的三维剂量-干预持续时间-疗效模型。结果:共纳入20项研究,44项独立实验,1019只动物。荟萃分析显示,槲皮素可显著减轻PF动物模型的肺病理组织评分和肺纤维化标志物的表达。此外,槲皮素还能显著改善炎症反应、氧化应激、上皮-间质转化和肌成纤维细胞活化、细胞衰老和凋亡以及细胞外基质(ECM)沉积标志物的表达。槲皮素无明显的肝、肾毒性。3D给药-干预持续时间-疗效模型显示,给药周期为20天以上,给药范围为5-100 mg/kg。结论:我们的研究强调了槲皮素治疗PF的潜力和可能的机制。
Use quercetin for pulmonary fibrosis: a preclinical systematic review and meta-analysis.
Background: Pulmonary fibrosis (PF) is an age-related interstitial lung disease, which lacks effective drug treatment at present. Quercetin has been shown to have favorable anti-inflammatory and anti-fibrotic properties, and preliminary evidence suggests its potential efficacy and tolerability in PF patients. However, a comprehensive systematic review and evaluation of the protective effects and potential mechanisms of quercetin in PF models remains to be completed. Therefore, we conducted this study.
Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched up to the April 1, 2024. CAMARADES was the methodological quality assessment tool. And statistical analyses were conducted with R and Stata 16.0. Origin was used for a three-dimensional (3D) dosage-intervention duration-efficacy model for quercetin treatment of PF.
Results: A total of 20 studies, encompassing 44 independent experiments and involving 1019 animals, were included in the analysis. Meta-analysis revealed that quercetin significantly mitigated lung pathological tissue scores and the expression of lung fibrosis markers in PF animal models. Furthermore, quercetin significantly ameliorated inflammatory responses, oxidative stress, epithelial-mesenchymal transition and myofibroblast activation, cell senescence and apoptosis, and the markers expression of extracellular matrix (ECM) deposition. Quercetin did not show significant hepatic and nephrotoxicity. The 3D dosage-intervention duration-efficacy model indicated that a dosing period over 20 days and dosages range of 5-100 mg/kg were appropriate modalities.
Conclusion: Herein, our study highlights the potential of quercetin in the treatment of PF and the available mechanisms.
期刊介绍:
Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas:
-Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states
-Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs
-Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents
-Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain
-Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs
-Muscle-immune interactions during inflammation [...]