Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways

Abstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary d...

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Main Authors: Jia-Qian Zhu, Yuan-Yang Tian, Kam Leung Chan, Zhen Hu, Qing-Qing Xu, Zhi-Xiu Lin, Yan-Fang Xian
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-024-00882-5
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author Jia-Qian Zhu
Yuan-Yang Tian
Kam Leung Chan
Zhen Hu
Qing-Qing Xu
Zhi-Xiu Lin
Yan-Fang Xian
author_facet Jia-Qian Zhu
Yuan-Yang Tian
Kam Leung Chan
Zhen Hu
Qing-Qing Xu
Zhi-Xiu Lin
Yan-Fang Xian
author_sort Jia-Qian Zhu
collection DOAJ
description Abstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. Methods BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. Results MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. Conclusions MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.
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spelling doaj.art-f461ee3ddee14c349880699c64d843622024-01-21T12:35:24ZengBMCChinese Medicine1749-85462024-01-0119111710.1186/s13020-024-00882-5Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathwaysJia-Qian Zhu0Yuan-Yang Tian1Kam Leung Chan2Zhen Hu3Qing-Qing Xu4Zhi-Xiu Lin5Yan-Fang Xian6School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong KongAbstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. Methods BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. Results MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. Conclusions MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.https://doi.org/10.1186/s13020-024-00882-5Modified Qing-Zao-Jiu-Fei Decoction (M-QZJFD)BleomycinPulmonary fibrosisOxidative stressNF-κB/Nrf2 pathwayMAPKs pathway
spellingShingle Jia-Qian Zhu
Yuan-Yang Tian
Kam Leung Chan
Zhen Hu
Qing-Qing Xu
Zhi-Xiu Lin
Yan-Fang Xian
Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
Chinese Medicine
Modified Qing-Zao-Jiu-Fei Decoction (M-QZJFD)
Bleomycin
Pulmonary fibrosis
Oxidative stress
NF-κB/Nrf2 pathway
MAPKs pathway
title Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
title_full Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
title_fullStr Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
title_full_unstemmed Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
title_short Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways
title_sort modified qing zao jiu fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating nrf2 nf κb and mapks pathways
topic Modified Qing-Zao-Jiu-Fei Decoction (M-QZJFD)
Bleomycin
Pulmonary fibrosis
Oxidative stress
NF-κB/Nrf2 pathway
MAPKs pathway
url https://doi.org/10.1186/s13020-024-00882-5
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