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紫锥菊通过调节NADPH氧化酶-4和内皮素-1/结缔组织生长因子/基质金属蛋白酶信号轴改善博来霉素诱导的大鼠肺纤维化。

Echinacea purpurea ameliorates Bleomycin-induced pulmonary fibrosis in rats through modulating NADPH oxidase-4 and endothelin-1/connective tissue growth factor/matrix metalloproteinases signalling axis.

作者信息

Salama Abeer A A, Elgohary Rania, Elwahab Sahar Abd, Mostafa Rasha E

机构信息

Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre (ID: 60014618), 33 ELBohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Cairo, Egypt.

Narcotics, Ergogenics and Poisons Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, Egypt.

出版信息

Sci Rep. 2025 Sep 2;15(1):32332. doi: 10.1038/s41598-025-06559-9.


DOI:10.1038/s41598-025-06559-9
PMID:40897757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12405438/
Abstract

Idiopathic pulmonary fibrosis (IPF) is one of the rapidly progressing interstitial lung illnesses. Bleomycin (Bleo) is used as a chemotherapeutic agent for the treatment of lymphoma patients. The major side effects of Bleo include lung fibrosis, characterized by the accumulation of inflammatory cells. Echinacea purpurea (ECH) possesses immune-modulating, antiviral, antimicrobial and anti-inflammatory activities. The current study aims to evaluate the possible protective effects of ECH against Bleomycin-induced pulmonary fibrosis. Forty rats were divided into four groups (n = 10). Group I represented the normal-control group. Group II represented the Bleo-control group. Groups III and IV received intra-tracheal Bleo followed by oral ECH (25 and 50 mg/kg); respectively, for 1 month. Lung tissue contents of reduced glutathione (GSH), malondialdehyde (MDA), transforming growth factor-beta (TGF-β), matrix metalloproteinases (MMP-2 & MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), MMP-9/TIMP-1 ratio, collagen-1 and alpha-Smooth muscle actin (α-SMA) were measured. NADPH oxidase 4 (NOX4), connective tissue growth factor (CTGF) and endothelin-1 (ET-1) genes were quantified using PCR. Moreover, lung tissue histopathological changes were screened. Intra-tracheal Bleo instillation resulted in significant increments in the lung tissue contents of MDA, TGF-β, MMP-2 & MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, collagen-1 and α-SMA. Moreover, Bleo significantly elevated the PCR expression of NOX4, CTGF and ET-1 genes in lung tissues and caused apparent lung tissue histopathological fibrotic changes. ECH treatment ameliorated all the aforementioned parameters and mitigated the lung tissue histopathological fibrotic changes induced by Bleo. The study highlighted for the first time the anti-oxidant, anti-inflammatory and anti-fibrotic effects of ECH against Bleo-induced pulmonary fibrosis in rats. The study suggests that these effects are mainly mediated via the modulation of Gelatinases, NOX4, ET-1 and CTGF. Accordingly, ECH is anticipated as a potential therapy to be added to the treatment regimen of pulmonary fibrosis.

摘要

特发性肺纤维化(IPF)是进展迅速的间质性肺疾病之一。博来霉素(Bleo)用作治疗淋巴瘤患者的化疗药物。博来霉素的主要副作用包括肺纤维化,其特征为炎症细胞积聚。紫锥菊(ECH)具有免疫调节、抗病毒、抗菌和抗炎活性。本研究旨在评估紫锥菊对博来霉素诱导的肺纤维化的可能保护作用。将40只大鼠分为四组(n = 10)。第一组为正常对照组。第二组为博来霉素对照组。第三组和第四组经气管内给予博来霉素,随后分别口服紫锥菊(25和50mg/kg),持续1个月。测定肺组织中还原型谷胱甘肽(GSH)、丙二醛(MDA)、转化生长因子-β(TGF-β)、基质金属蛋白酶(MMP-2和MMP-9)、金属蛋白酶组织抑制剂1(TIMP-1)、MMP-9/TIMP-1比值、胶原蛋白-1和α-平滑肌肌动蛋白(α-SMA)的含量。使用聚合酶链反应(PCR)对烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)、结缔组织生长因子(CTGF)和内皮素-1(ET-1)基因进行定量分析。此外,对肺组织的组织病理学变化进行筛查。经气管内滴注博来霉素导致肺组织中MDA、TGF-β、MMP-2、MMP-9、TIMP-1、MMP-9/TIMP-1比值、胶原蛋白-1和α-SMA的含量显著增加。此外,博来霉素显著提高了肺组织中NOX4、CTGF和ET-1基因的PCR表达,并引起明显的肺组织组织病理学纤维化改变。紫锥菊治疗改善了上述所有参数,并减轻了博来霉素诱导的肺组织组织病理学纤维化改变。该研究首次强调了紫锥菊对博来霉素诱导的大鼠肺纤维化的抗氧化、抗炎和抗纤维化作用。该研究表明,这些作用主要通过调节明胶酶、NOX4、ET-1和CTGF来介导。因此,紫锥菊有望作为一种潜在的治疗方法添加到肺纤维化的治疗方案中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/608a6d889fba/41598_2025_6559_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/11a1cf079f53/41598_2025_6559_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/d60beac656bc/41598_2025_6559_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/608a6d889fba/41598_2025_6559_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/312dc09b697a/41598_2025_6559_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/663cf4b7d67d/41598_2025_6559_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/66782b68ab1d/41598_2025_6559_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/51c77c12e166/41598_2025_6559_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/11a1cf079f53/41598_2025_6559_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/d60beac656bc/41598_2025_6559_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e2/12405438/608a6d889fba/41598_2025_6559_Fig7_HTML.jpg

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本文引用的文献

[1]
Matrix metalloproteinases and their tissue inhibitors as upcoming biomarker signatures of connective tissue diseases-related interstitial lung disease: towards an earlier and accurate diagnosis.

Mol Med. 2025-2-20

[2]
MPT0E028, a novel pan-HDAC inhibitor, prevents pulmonary fibrosis through inhibition of TGF-β-induced CTGF expression in human lung fibroblasts: Involvement of MKP-1 activation.

Eur J Pharmacol. 2024-8-15

[3]
Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Biomed Pharmacother. 2024-4

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Echinacea Polyphenols Inhibit NLRP3-Dependent Pyroptosis, Apoptosis, and Necroptosis via Suppressing NO Production during Lipopolysaccharide-Induced Acute Lung Injury.

J Agric Food Chem. 2023-5-17

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Ezetimibe alleviates acetic acid-induced ulcerative colitis in rats: targeting the Akt/NF-κB/STAT3/CXCL10 signaling axis.

J Pharm Pharmacol. 2023-4-7

[6]
Endothelin-1 as a Biomarker of Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease Associated with Autoimmune Diseases.

Int J Mol Sci. 2023-1-9

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Lactoferrin mitigates ethanol-induced gastric ulcer via modulation of ROS/ICAM-1/Nrf2 signaling pathway in Wistar rats.

Iran J Basic Med Sci. 2022-12

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Protective effects of royal jelly and against moxifloxacin-induced renal and hepatic injury in rats.

Drug Chem Toxicol. 2023-11

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Plumbagin attenuates Bleomycin-induced lung fibrosis in mice.

Allergy Asthma Clin Immunol. 2022-10-21

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Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice.

Respir Res. 2022-7-8

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