Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from <i>Corydalis edulis</i>, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The ai...

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Main Authors: Yifan Tu, Xiaodong Li, Yuanzheng Fu, Yunyun Chen, Hui Fang, Yuan Li, Ying Gu, Jiawei Zhang
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/5/4629
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author Yifan Tu
Xiaodong Li
Yuanzheng Fu
Yunyun Chen
Hui Fang
Yuan Li
Ying Gu
Jiawei Zhang
author_facet Yifan Tu
Xiaodong Li
Yuanzheng Fu
Yunyun Chen
Hui Fang
Yuan Li
Ying Gu
Jiawei Zhang
author_sort Yifan Tu
collection DOAJ
description Isocorydine (ICD) is a type of isoquinoline alkaloid originating from <i>Corydalis edulis</i>, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.
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spelling doaj.art-2fa30eef27dc47d0964beb1ae5bae0632023-11-17T07:51:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245462910.3390/ijms24054629Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by LipopolysaccharideYifan Tu0Xiaodong Li1Yuanzheng Fu2Yunyun Chen3Hui Fang4Yuan Li5Ying Gu6Jiawei Zhang7Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, ChinaInstitute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaInstitute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaInstitute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaInstitute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaInstitute of Genetics, Department of Human Genetics, Zhejiang University School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, ChinaKey Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, ChinaKey Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, ChinaIsocorydine (ICD) is a type of isoquinoline alkaloid originating from <i>Corydalis edulis</i>, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.https://www.mdpi.com/1422-0067/24/5/4629isocorydinelipopolysaccharideinterleukin-6macrophagesacute lung injury
spellingShingle Yifan Tu
Xiaodong Li
Yuanzheng Fu
Yunyun Chen
Hui Fang
Yuan Li
Ying Gu
Jiawei Zhang
Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
International Journal of Molecular Sciences
isocorydine
lipopolysaccharide
interleukin-6
macrophages
acute lung injury
title Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
title_full Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
title_fullStr Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
title_full_unstemmed Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
title_short Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide
title_sort isocorydine ameliorates il 6 expression in bone marrow derived macrophages and acute lung injury induced by lipopolysaccharide
topic isocorydine
lipopolysaccharide
interleukin-6
macrophages
acute lung injury
url https://www.mdpi.com/1422-0067/24/5/4629
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