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Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics

BACKGROUND: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer’s disease. AIM OF THE STUDY: To elucidate the mechanism by which S. baicalensis modulates lipid meta...

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Autores principales: Ge, Ping-Yuan, Qi, Yi-Yu, Qu, Shu-Yue, Zhao, Xin, Ni, Sai-jia, Yao, Zeng-Ying, Guo, Rui, Yang, Nian-Yun, Zhang, Qi-Chun, Zhu, Hua-Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106469/
https://www.ncbi.nlm.nih.gov/pubmed/33976541
http://dx.doi.org/10.2147/DDDT.S301679
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author Ge, Ping-Yuan
Qi, Yi-Yu
Qu, Shu-Yue
Zhao, Xin
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Zhang, Qi-Chun
Zhu, Hua-Xu
author_facet Ge, Ping-Yuan
Qi, Yi-Yu
Qu, Shu-Yue
Zhao, Xin
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Zhang, Qi-Chun
Zhu, Hua-Xu
author_sort Ge, Ping-Yuan
collection PubMed
description BACKGROUND: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer’s disease. AIM OF THE STUDY: To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. MATERIALS AND METHODS: The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. RESULTS: Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. CONCLUSION: According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis, may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics.
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spelling pubmed-81064692021-05-10 Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics Ge, Ping-Yuan Qi, Yi-Yu Qu, Shu-Yue Zhao, Xin Ni, Sai-jia Yao, Zeng-Ying Guo, Rui Yang, Nian-Yun Zhang, Qi-Chun Zhu, Hua-Xu Drug Des Devel Ther Original Research BACKGROUND: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer’s disease. AIM OF THE STUDY: To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. MATERIALS AND METHODS: The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. RESULTS: Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. CONCLUSION: According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis, may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics. Dove 2021-05-04 /pmc/articles/PMC8106469/ /pubmed/33976541 http://dx.doi.org/10.2147/DDDT.S301679 Text en © 2021 Ge et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ge, Ping-Yuan
Qi, Yi-Yu
Qu, Shu-Yue
Zhao, Xin
Ni, Sai-jia
Yao, Zeng-Ying
Guo, Rui
Yang, Nian-Yun
Zhang, Qi-Chun
Zhu, Hua-Xu
Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title_full Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title_fullStr Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title_full_unstemmed Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title_short Potential Mechanism of S. baicalensis on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics
title_sort potential mechanism of s. baicalensis on lipid metabolism explored via network pharmacology and untargeted lipidomics
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106469/
https://www.ncbi.nlm.nih.gov/pubmed/33976541
http://dx.doi.org/10.2147/DDDT.S301679
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