The Inefficiency of Low-concentration Curcumin Intervention in Ameliorating Chronic-stage Pulmonary Fibrosis

Q2 Pharmacology, Toxicology and Pharmaceutics Current Bioactive Compounds Pub Date : 2023-08-10 DOI:10.2174/1573407219666230810094839
F. Muneesa M, Y. Bhandary
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Abstract

Curcumin, a polyphenol compound, is reported to exhibit ameliorative effects in acute lung injury and different organ fibrosis models. We have previously demonstrated that curcumin, at a dose of 75 mg/kg, could modulate inflammatory mediators and fibrinolytic system proteins in the inflammatory stage as well as fibroproliferative stage in a mouse model of bleomycin (BLM) induced pulmonary fibrosis. In this study, we investigated the efficacy of the same dose of curcumin in resolving the established fibrotic stage in a mouse model of BLM-induced pulmonary fibrosis. We prepared the fibrosis model by intranasal administration of BLM (2 mg/kg). Curcumin intervention was performed by intraperitoneal injection on 16th to 20th days post BLM exposure. The control group was administered with normal saline. The mice were sacrificed on the 21st day post BLM exposure. Histological analysis of the lung tissue samples indicated that curcumin (75 mg/kg) could not reverse the fibrotic features induced by BLM. We also performed RT-PCR and western blot to examine the molecular changes induced by BLM and curcumin. It was observed that curcumin could neither reduce the expressions of fibrotic markers nor restore the normal expressions of proteins in the fibrinolytic system. Our data suggest that a low dose of curcumin is not effective in ameliorating the fibrotic stage of BLM-induced pulmonary fibrosis. An increased dose or a formulation that increases the bioavailability of curcumin could probably exhibit promising effects against pulmonary fibrosis in the future.
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低浓度姜黄素干预改善慢性肺纤维化的无效性
姜黄素是一种多酚化合物,据报道在急性肺损伤和不同器官纤维化模型中表现出改善作用。我们之前已经证明,在博来霉素(BLM)诱导的肺纤维化小鼠模型中,75 mg/kg剂量的姜黄素可以调节炎症介质和纤维蛋白溶解系统蛋白在炎症期和纤维增殖期。在这项研究中,我们研究了相同剂量的姜黄素对blm诱导的肺纤维化小鼠模型中已建立的纤维化阶段的影响。我们通过鼻给药BLM (2 mg/kg)制备纤维化模型。于BLM暴露后第16 ~ 20天腹腔注射姜黄素干预。对照组给予生理盐水治疗。小鼠于BLM暴露后第21天处死。肺组织样本的组织学分析表明,姜黄素(75 mg/kg)不能逆转BLM诱导的纤维化特征。采用RT-PCR和western blot检测BLM和姜黄素诱导的分子变化。观察到姜黄素既不能降低纤维化标志物的表达,也不能恢复纤溶系统蛋白的正常表达。我们的数据表明,低剂量的姜黄素对改善blm诱导的肺纤维化的纤维化阶段无效。增加姜黄素的剂量或增加姜黄素生物利用度的配方可能会在未来显示出对抗肺纤维化的良好效果。
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来源期刊
Current Bioactive Compounds
Current Bioactive Compounds Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.90
自引率
0.00%
发文量
112
期刊介绍: The journal aims to provide comprehensive review articles on new bioactive compounds with proven activities in various biological screenings and pharmacological models with a special emphasis on stereoeselective synthesis. The aim is to provide a valuable information source of bioactive compounds synthesized or isolated, which can be used for further development of pharmaceuticals by industry and academia. The journal should prove to be essential reading for pharmacologists, natural product chemists and medicinal chemists who wish to be kept informed and up-to-date with the most important developments on new bioactive compounds of natural or synthetic origin, including their stereoeselective synthesis.
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