Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions
Momordicoside G is a bioactive component from Momordica charantia, this study explores the contributions of macrophages to the effects of momordicoside G on lung injury and carcinoma lesion. In vitro, when administered at the dose that has no effect on cell viability in M2-like macrophages, momordic...
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2019-03-01
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doaj-de4f2be2d2e34c9cb03e4fd1efe5a3392020-11-24T21:42:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-03-011010.3389/fphar.2019.00321441448Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma LesionsZhenhua Du0Shuhui Zhang1Yukun Lin2Lin Zhou3Yuehua Wang4Guixi Yan5Mengdi Zhang6Mengqi Wang7Jiahuan Li8Qiaozhen Tong9Yongjian Duan10Gangjun Du11Gangjun Du12Institute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Oncology, The First Affiliated Hospital of Henan University, Kaifeng, ChinaInstitute of Pharmacy, College of Pharmacy, Henan University, Kaifeng, ChinaSchool of Pharmacy and Chemical Engineering, Zhengzhou University of Industrial Technology, Xinzheng, ChinaMomordicoside G is a bioactive component from Momordica charantia, this study explores the contributions of macrophages to the effects of momordicoside G on lung injury and carcinoma lesion. In vitro, when administered at the dose that has no effect on cell viability in M2-like macrophages, momordicoside G decreased ROS and promoted autophagy and thus induced apoptosis in M1-like macrophages with the morphological changes. In the urethane-induced lung carcinogenic model, prior to lung carcinoma lesions, urethane induced obvious lung injury accompanied by the increased macrophage infiltration. The lung carcinoma lesions were positively correlated with lung tissue injury and macrophage infiltration in alveolar cavities in the control group, these macrophages showed mainly a M1-like (iNOS+/CD68+) phenotype. ELISA showed that the levels of IL-6 and IL-12 were increased and the levels of IL-10 and TGF-β1 were reduced in the control group. After momordicoside G treatment, lung tissue injury and carcinoma lesions were ameliorated with the decreased M1-like macrophages and the increased M2-like (arginase+/CD68+) macrophages, whereas macrophage depletion by liposome-encapsulated clodronate (LEC) decreased significantly lung tissue injury and carcinoma lesions and also attenuated the protective efficacy of momordicoside G. The M2 macrophage dependent efficacy of momordicoside G was confirmed in a LPS-induced lung injury model in which epithelial closure was promoted by the transfer of M2-like macrophages and delayed by the transfer of M1-like macrophages. To acquire further insight into the underlying molecular mechanisms by which momordicoside G regulates M1 macrophages, we conduct a comprehensive bioinformatics analysis of momordicoside G relevant targets and pathways involved in M1 macrophage phenotype. This study suggests a function of momordicoside G, whereby it selectively suppresses M1 macrophages to stimulate M2-associated lung injury repair and prevent inflammation-associated lung carcinoma lesions.https://www.frontiersin.org/article/10.3389/fphar.2019.00321/fullmomordicoside Gmacrophage phenotypeslung injurycarcinoma lesionsinjury repair |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhenhua Du Shuhui Zhang Yukun Lin Lin Zhou Yuehua Wang Guixi Yan Mengdi Zhang Mengqi Wang Jiahuan Li Qiaozhen Tong Yongjian Duan Gangjun Du Gangjun Du |
spellingShingle |
Zhenhua Du Shuhui Zhang Yukun Lin Lin Zhou Yuehua Wang Guixi Yan Mengdi Zhang Mengqi Wang Jiahuan Li Qiaozhen Tong Yongjian Duan Gangjun Du Gangjun Du Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions Frontiers in Pharmacology momordicoside G macrophage phenotypes lung injury carcinoma lesions injury repair |
author_facet |
Zhenhua Du Shuhui Zhang Yukun Lin Lin Zhou Yuehua Wang Guixi Yan Mengdi Zhang Mengqi Wang Jiahuan Li Qiaozhen Tong Yongjian Duan Gangjun Du Gangjun Du |
author_sort |
Zhenhua Du |
title |
Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions |
title_short |
Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions |
title_full |
Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions |
title_fullStr |
Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions |
title_full_unstemmed |
Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions |
title_sort |
momordicoside g regulates macrophage phenotypes to stimulate efficient repair of lung injury and prevent urethane-induced lung carcinoma lesions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-03-01 |
description |
Momordicoside G is a bioactive component from Momordica charantia, this study explores the contributions of macrophages to the effects of momordicoside G on lung injury and carcinoma lesion. In vitro, when administered at the dose that has no effect on cell viability in M2-like macrophages, momordicoside G decreased ROS and promoted autophagy and thus induced apoptosis in M1-like macrophages with the morphological changes. In the urethane-induced lung carcinogenic model, prior to lung carcinoma lesions, urethane induced obvious lung injury accompanied by the increased macrophage infiltration. The lung carcinoma lesions were positively correlated with lung tissue injury and macrophage infiltration in alveolar cavities in the control group, these macrophages showed mainly a M1-like (iNOS+/CD68+) phenotype. ELISA showed that the levels of IL-6 and IL-12 were increased and the levels of IL-10 and TGF-β1 were reduced in the control group. After momordicoside G treatment, lung tissue injury and carcinoma lesions were ameliorated with the decreased M1-like macrophages and the increased M2-like (arginase+/CD68+) macrophages, whereas macrophage depletion by liposome-encapsulated clodronate (LEC) decreased significantly lung tissue injury and carcinoma lesions and also attenuated the protective efficacy of momordicoside G. The M2 macrophage dependent efficacy of momordicoside G was confirmed in a LPS-induced lung injury model in which epithelial closure was promoted by the transfer of M2-like macrophages and delayed by the transfer of M1-like macrophages. To acquire further insight into the underlying molecular mechanisms by which momordicoside G regulates M1 macrophages, we conduct a comprehensive bioinformatics analysis of momordicoside G relevant targets and pathways involved in M1 macrophage phenotype. This study suggests a function of momordicoside G, whereby it selectively suppresses M1 macrophages to stimulate M2-associated lung injury repair and prevent inflammation-associated lung carcinoma lesions. |
topic |
momordicoside G macrophage phenotypes lung injury carcinoma lesions injury repair |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00321/full |
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