Caulerpa okamurae extract alleviates pulmonary fibrosis in vitro and in vivo by modulating Tgfβ/SMAD/MAPK signaling and NLRP3 inflammasome activation

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2025-03-19 DOI:10.1016/j.jff.2025.106734

Seok Hee Seo , Thi My Tien Truong , Hyejin Hyeon , Young-Min Ham , Yong-Hwan Jung , Hyun-Jin Kim , Dong-Shin Kim , Inhae Kang

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Abstract

Pulmonary fibrosis (PF) characterized by fibroblast dysfunction and inflammation, in driven by transforming growth factor beta (Tgfβ) plays a crucial role. Caulerpa okamurae extract (COE), drived from a green seaweed widely consumed in East Asia, is known for its anti-obesity properties, but its effects on PF remain unexplored. This study investigated the potential of the COE in PF using Tgfβ-stimulated MRC-5 lung fibroblasts and bleomycin (BLM)-induced PF in C57BL/6 mice. In vitro, COE significantly reduced fibrotic markers (α-Sma, Mmp1, Col1a1, and Vimentin) and suppressed inflammatory mediators (Il-1β, Il-6, and Cox2) by downregulating Tgfβ/SMAD2/3 and MAPK signaling. In vivo, COE attenuated fibrotic features in BLM-treated mice by modulating the Tgfβ/SMAD/MAPK pathway. Interestingly, COE decreased plasma levels of IL-1β, an indicative of suppressed NLRP3 inflammasome activation. This effect was further validated in lipopolysaccharide and nigericin-treated bone marrow-derived macrophages, where COE inhibited NLRP3 inflammasome activation. These finding highlight COE's action in mitigating fibrosis and inflammation by modulation of Tgfβ/SMAD2/3 and MAPK signaling, along with the NLRP3 inflammasome pathway, underscoring its potential as a novel therapeutic for PF.

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肺纤维化（PF）以成纤维细胞功能障碍和炎症为特征，其中转化生长因子β（Tgfβ）起着至关重要的作用。褐藻提取物（Caulerpa okamurae extract，COE）是从一种在东亚广泛食用的绿藻中提取出来的，以其抗肥胖特性而闻名，但其对肺纤维化的影响仍有待探索。本研究利用Tgfβ刺激的MRC-5肺成纤维细胞和博来霉素（BLM）诱导的C57BL/6小鼠PF，研究了COE对PF的潜在作用。在体外，COE通过下调Tgfβ/SMAD2/3和MAPK信号转导，明显减少了纤维化标志物（α-Sma、Mmp1、Col1a1和Vimentin），并抑制了炎症介质（Il-1β、Il-6和Cox2）。在体内，COE 通过调节 Tgfβ/SMAD/MAPK 通路，减轻了 BLM 处理的小鼠的纤维化特征。有趣的是，COE降低了血浆中IL-1β的水平，这表明NLRP3炎性体的激活受到了抑制。这一效应在脂多糖和尼格瑞辛处理的骨髓巨噬细胞中得到了进一步验证，COE抑制了NLRP3炎性体的活化。这些发现凸显了COE通过调节Tgfβ/SMAD2/3和MAPK信号以及NLRP3炎性体通路来减轻纤维化和炎症的作用，强调了它作为一种新型PF疗法的潜力。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.