Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis
Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), whic...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.915161/full |
| _version_ | 1811183146726588416 |
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| author | Longping Peng Mengjiao Ma Yidan Dong Qiong Wu Shiying An Min Cao Yi Wang Chang Zhou Maolin Zhou Xu Wang Qianqian Liang Qianqian Liang Qianqian Liang Youhua Wang |
| author_facet | Longping Peng Mengjiao Ma Yidan Dong Qiong Wu Shiying An Min Cao Yi Wang Chang Zhou Maolin Zhou Xu Wang Qianqian Liang Qianqian Liang Qianqian Liang Youhua Wang |
| author_sort | Longping Peng |
| collection | DOAJ |
| description | Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis.Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot.Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury.Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB. |
| first_indexed | 2024-04-11T09:42:55Z |
| format | Article |
| id | doaj.art-37f9f0cb4d5842a99aced58d8ab59534 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T09:42:55Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-37f9f0cb4d5842a99aced58d8ab595342022-12-22T04:31:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.915161915161Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysisLongping Peng0Mengjiao Ma1Yidan Dong2Qiong Wu3Shiying An4Min Cao5Yi Wang6Chang Zhou7Maolin Zhou8Xu Wang9Qianqian Liang10Qianqian Liang11Qianqian Liang12Youhua Wang13Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Cancer Center, Fudan University, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSpine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackground: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis.Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot.Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury.Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB.https://www.frontiersin.org/articles/10.3389/fphar.2022.915161/fullKuoxin Decoctionlymphangiogenesiszebrafishlymphatic endothelial cellssalvianolic acid Bnetwork analysis |
| spellingShingle | Longping Peng Mengjiao Ma Yidan Dong Qiong Wu Shiying An Min Cao Yi Wang Chang Zhou Maolin Zhou Xu Wang Qianqian Liang Qianqian Liang Qianqian Liang Youhua Wang Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis Frontiers in Pharmacology Kuoxin Decoction lymphangiogenesis zebrafish lymphatic endothelial cells salvianolic acid B network analysis |
| title | Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| title_full | Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| title_fullStr | Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| title_full_unstemmed | Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| title_short | Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| title_sort | kuoxin decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis |
| topic | Kuoxin Decoction lymphangiogenesis zebrafish lymphatic endothelial cells salvianolic acid B network analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.915161/full |
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