Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology

Abstract Scabiosa comosa and S. tschilliensis (SCST) are traditionally used for liver diseases in Mongolian medicine. However, their active ingredients and molecular mechanisms are unknown. The present study employed network pharmacology and experimental verification approaches to decipher the commo...

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Autores principales:	Qianwen Chen, Yuanyuan Wang, Feixiang Ma, Mengdi Han, Zhen Wang, Peifeng Xue, Jingkun Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4aeafc190ef4916a74efe0c7c6b1faf
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spelling	oai:doaj.org-article:c4aeafc190ef4916a74efe0c7c6b1faf2021-12-02T14:16:58ZSystematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology10.1038/s41598-021-81399-x2045-2322https://doaj.org/article/c4aeafc190ef4916a74efe0c7c6b1faf2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81399-xhttps://doaj.org/toc/2045-2322Abstract Scabiosa comosa and S. tschilliensis (SCST) are traditionally used for liver diseases in Mongolian medicine. However, their active ingredients and molecular mechanisms are unknown. The present study employed network pharmacology and experimental verification approaches to decipher the common pharmacological mechanisms of SCST on liver fibrosis, which is the key step in liver diseases. We predicted the targets of all available SCST ingredients with the SWISS and SuperPred servers and clustered the targets related to liver fibrosis from DrugBank, the OMIM database and the literature. We further evaluated the links between the herbal ingredients and pharmacological actions to explore the potential mechanism of action of SCST. We found that the PPARG signalling pathway could be regulated by SCST for liver fibrosis through enrichment analysis. The key targets included 8 co-targets, including HSP90AA1, PPARG, HSP90AB1, STAT1, etc., which play pivotal roles in the pathogenesis of liver fibrosis. Additionally, the top 15 key compounds included flavonoids and phenylpropanoids. Central to the pathogenesis of liver fibrosis is trans-differentiation or activation of hepatic stellate cells (HSCs). Therefore, LX2 cells, an immortalized human HSC line, were studied. Here, a total 37 components were isolated and identified from the inflorescences of SCST, including the new compound tschilliensisin, and the first separated components, β-sitosterol and luteolin, and these compounds were assessed against anti-hepatic fibrosis. An MTT assay and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses demonstrated that the flavonoids of SCST revealed anti-hepatic fibrosis effects via anti-proliferation and increases in the Stat1, Pparg, Hsp90aa1 genes and STAT1 and PPARG proteins in LX-2 cells. In conclusion, these results indicate that SCST has multi-targeted and multi-component synergistic anti-hepatic fibrosis effects.Qianwen ChenYuanyuan WangFeixiang MaMengdi HanZhen WangPeifeng XueJingkun LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qianwen Chen Yuanyuan Wang Feixiang Ma Mengdi Han Zhen Wang Peifeng Xue Jingkun Lu Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
description	Abstract Scabiosa comosa and S. tschilliensis (SCST) are traditionally used for liver diseases in Mongolian medicine. However, their active ingredients and molecular mechanisms are unknown. The present study employed network pharmacology and experimental verification approaches to decipher the common pharmacological mechanisms of SCST on liver fibrosis, which is the key step in liver diseases. We predicted the targets of all available SCST ingredients with the SWISS and SuperPred servers and clustered the targets related to liver fibrosis from DrugBank, the OMIM database and the literature. We further evaluated the links between the herbal ingredients and pharmacological actions to explore the potential mechanism of action of SCST. We found that the PPARG signalling pathway could be regulated by SCST for liver fibrosis through enrichment analysis. The key targets included 8 co-targets, including HSP90AA1, PPARG, HSP90AB1, STAT1, etc., which play pivotal roles in the pathogenesis of liver fibrosis. Additionally, the top 15 key compounds included flavonoids and phenylpropanoids. Central to the pathogenesis of liver fibrosis is trans-differentiation or activation of hepatic stellate cells (HSCs). Therefore, LX2 cells, an immortalized human HSC line, were studied. Here, a total 37 components were isolated and identified from the inflorescences of SCST, including the new compound tschilliensisin, and the first separated components, β-sitosterol and luteolin, and these compounds were assessed against anti-hepatic fibrosis. An MTT assay and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses demonstrated that the flavonoids of SCST revealed anti-hepatic fibrosis effects via anti-proliferation and increases in the Stat1, Pparg, Hsp90aa1 genes and STAT1 and PPARG proteins in LX-2 cells. In conclusion, these results indicate that SCST has multi-targeted and multi-component synergistic anti-hepatic fibrosis effects.
format	article
author	Qianwen Chen Yuanyuan Wang Feixiang Ma Mengdi Han Zhen Wang Peifeng Xue Jingkun Lu
author_facet	Qianwen Chen Yuanyuan Wang Feixiang Ma Mengdi Han Zhen Wang Peifeng Xue Jingkun Lu
author_sort	Qianwen Chen
title	Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
title_short	Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
title_full	Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
title_fullStr	Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
title_full_unstemmed	Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology
title_sort	systematic profiling of the effective ingredients and mechanism of scabiosa comosa and s. tschilliensis against hepatic fibrosis combined with network pharmacology
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c4aeafc190ef4916a74efe0c7c6b1faf
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Systematic profiling of the effective ingredients and mechanism of Scabiosa comosa and S. tschilliensis against hepatic fibrosis combined with network pharmacology

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