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Protective effects and mechanism of curcumin in animal models of pulmonary fibrosis: a preclinical systematic review and meta-analysis.

ABSTRACT: Introduction: At present, there is a lack of effective treatment for pulmonary fibrosis (PF), and a number of studies have confirmed that curcumin (CUR) has a good effect on PF. Research Qusetion: Is CUR effective in preclinical trials for PF and what is its mechanism of action? Methods: Animal reports of PF treated with CUR were searched from Pubmed, Embase, Web of Science and Cochrane Library from 1 January 2000 to 19 April 2023 to compare CUR treatment of PF with a no-intervention model group. A previous registration (nsply registration number: INPLASY202360084) of this review protocol was undertaken. Results: The meta-analysis included 27 publications and 29 studies involving 396 animals. CUR significantly improved the degree of fibrosis, levels of inflammation, and oxidative imbalances in lung tissue in animal models of PF. In terms fibrosis, such as HYP content (SMD = -4.96; 95% CI = -6.05 to -3.87; p = 0.000).In terms of inflammatory indicators, such as MPO activity (SMD = -2.12; 95% CI = -4.93 to 0.69; p = 0.000). In terms of oxidation index, such as MDA (SMD = -5.63; 95% CI = -9.66 to -1.6; p = 0.000). Conclusion: CUR significantly improved the degree of fibrosis, levels of inflammation, and oxidative imbalances in lung tissue in animal models of PF. Due to the quantitative and qualitative limitations of current research, more high-quality studies are needed to verify the above conclusion.

SUBMITTER: Hanyu F

PROVIDER: S-EPMC10613035 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Protective effects and mechanism of curcumin in animal models of pulmonary fibrosis: a preclinical systematic review and meta-analysis.

Hanyu Fang F Zheng Hong H Jiaqi Wang W Tairan Dong D Yiyuanzi Zhao Z Qiwen Yang Y Ying Liu L Hongchun Zhang Z Lu Liu L

Frontiers in pharmacology 20231013

Introduction: At present, there is a lack of effective treatment for pulmonary fibrosis (PF), and a number of studies have confirmed that curcumin (CUR) has a good effect on PF. Research Qusetion: Is CUR effective in preclinical trials for PF and what is its mechanism of action? Methods: Animal reports of PF treated with CUR were searched from Pubmed, Embase, Web of Science and Cochrane Library from 1 January 2000 to 19 April 2023 to compare CUR treatment of PF with a no-int ...[more]

PMID: 37900163

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Project description:Background: Pulmonary fibrosis (PF) is a lung disease with no curative drug, characterized by a progressive decrease in lung function. Metformin (MET) is a hypoglycemic agent with the advantages of high safety and low cost and has been used in several in vivo trials to treat fibrotic diseases. Objective: This study aimed to explore the efficacy and safety of MET in treating PF and elaborate on its mechanism. Methods: Eight databases were searched for in vivo animal trials of MET for PF from the time of database creation until 1 March 2022. The risk of bias quality assessment of the included studies was conducted using SYRCLE's risk of bias assessment. Pulmonary inflammation and fibrosis scores were the primary outcomes of this study. Hydroxyproline (HYP), type I collagen (collagen I), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), Smad, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) protein expression in lung tissues and animal mortality were secondary outcomes. Effect magnitudes were combined and calculated using Revman 5.3 and Stata 16.0 to assess the efficacy and safety of MET in animal models of PF. Inter-study heterogeneity was examined using the I 2 or Q test, and publication bias was assessed using funnel plots and Egger's test. Results: A total of 19 studies involving 368 animals were included, with a mean risk of bias of 5.9. The meta-analysis showed that MET significantly suppressed the level of inflammation and degree of PF in the lung tissue of the PF animal model. MET also reduced the content of HYP, collagen I, α-SMA, and TGF-β and phosphorylation levels of Smad2, Smad3, p-smad2/3/smad2/3, ERK1/2, and p-ERK1/2/ERK1/2 in lung tissues. MET also elevated AMPK/p-AMPK levels in lung tissues and significantly reduced animal mortality. Conclusion: The results of this study suggest that MET has a protective effect on lung tissues in PF animal models and may be a potential therapeutic candidate for PF treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327285, identifier CRD42022327285.

Project description:UnlabelledIdiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much enthusiasm for the treatment of several conditions, including lung diseases. Human trials of mesenchymal stromal cell (MSC) therapy for pulmonary fibrosis are under way. To shed light on the potential usefulness of MSCs for human disease, we aimed to systematically review the preclinical literature to determine if MSCs are beneficial in animal bleomycin pulmonary fibrosis models. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal bleomycin models of pulmonary fibrosis. Studies using embryonic stem cells or induced pluripotent stem cells were excluded. Seventeen studies were selected, all of which used MSCs in rodents. MSC therapy led to an improvement in bleomycin-induced lung collagen deposition in animal lungs and in the pulmonary fibrosis Ashcroft score in most studies. MSC therapy improved histopathology in almost all studies in which it was evaluated qualitatively. Furthermore, MSC therapy was found to improve 14-day survival in animals with bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage total and neutrophil counts, as well as transforming growth factor-β levels, were also reduced by MSCs. MSCs are beneficial in rodent bleomycin pulmonary fibrosis models. Since most studies examined the initial inflammatory phase rather than the chronic fibrotic phase, preclinical data offer better support for human trials of MSCs in acute exacerbations of pulmonary fibrosis rather than the chronic phase of the disease.SignificanceThere has been increased interest in mesenchymal stromal cell therapy for lung diseases. A few small clinical trials are under way in idiopathic pulmonary fibrosis. Preclinical evidence was assessed in a systematic review, as is often done for clinical studies. The existing studies offer better support for efficacy in the initial inflammatory phase rather than the fibrotic phase that human trials are targeting.

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Project description:BackgroundPulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies.MethodsWe will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and individual study reporting will be assessed according to an itemized checklist based on the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines.DiscussionThis systematic review will examine the efficacy and safety of regenerative cell therapy in preclinical models of PAH. As well, the literature will be assessed for study quality and risk of bias. The results will guide the design of future clinical trials and preclinical animal studies.Systematic review registrationCAMARADES ( http://www.dcn.ed.ac.uk/camarades/SyRF/Protocols.htm ).

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Protective effects and mechanism of curcumin in animal models of pulmonary fibrosis: a preclinical systematic review and meta-analysis.

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Protective effects and mechanism of curcumin in animal models of pulmonary fibrosis: a preclinical systematic review and meta-analysis.

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